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Cited by 42Bacterial Genetics and BiotechnologyEscherichia coli research studiesAntibiotic Resistance in Bacteria

Siderophore-mediated iron acquisition by Klebsiella pneumoniae

Open access
Kumar, Ashish, Chakravorty, Somnath, Yang, Taihao, Russo, Thomas A., Newton, Salete M., Klebba, Phillip E.·2024·Journal of Bacteriology
DOI 10.1128/jb.00024-24PMC PMC11112993
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Abstract

Microbes synthesize and secrete siderophores, that bind and solubilize precipitated or otherwise unavailable iron in their microenvironments. Gram (−) bacterial TonB-dependent outer membrane receptors capture the resulting ferric siderophores to begin the uptake process. From their similarity to fepA, the structural gene for the Escherichia coli ferric enterobactin (FeEnt) receptor, we identified four homologous genes in the human and animal ESKAPE pathogen Klebsiella pneumoniae (strain Kp52.145). One locus encodes IroN (locus 0027 on plasmid pII), and three other loci encode other FepA orthologs/paralogs (chromosomal loci 1658, 2380, and 4984 ). Based on the crystal structure of E. coli FepA (1FEP), we modeled the tertiary structures of the K. pneumoniae FepA homologs and genetically engineered individual Cys substitutions in their predicted surface loops. We subjected bacteria expressing the Cys mutant proteins to modification with extrinsic fluorescein maleimide (FM) and used the resulting fluorescently labeled cells to spectroscopically monitor the binding and transport of catecholate ferric siderophores by the four different receptors. The FM-modified FepA homologs were nanosensors that defined the ferric catecholate uptake pathways in pathogenic strains of K. pneumoniae . In Kp52.145, loci 1658 and 4984 encoded receptors that primarily recognized and transported FeEnt; locus 0027 produced a receptor that principally bound and transported FeEnt and glucosylated FeEnt (FeGEnt); locus 2380 encoded a protein that bound ferric catecholate compounds but did not detectably transport them. The sensors also characterized the uptake of iron complexes, including FeGEnt, by the hypervirulent, hypermucoviscous K. pneumoniae strain hvKp1. IMPORTANCE: Both commensal and pathogenic bacteria produce small organic chelators, called siderophores, that avidly bind iron and increase its bioavailability. Klebsiella pneumoniae variably produces four siderophores that antagonize host iron sequestration: enterobactin, glucosylated enterobactin (also termed salmochelin), aerobactin, and yersiniabactin, which promote colonization of different host tissues. Abundant evidence links bacterial iron acquisition to virulence and infectious diseases. The data we report explain the recognition and transport of ferric catecholates and other siderophores, which are crucial to iron acquisition by K. pneumoniae .

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Crossref · 10.1128/jb.00024-24

Cites

62 of 66 references verified0 citation errors · 4 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

34 of 62 cited sources checked · 10 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    The elaboration and acquisition of the latter three siderophores are associated with the pathogenesis and hypervirulence of K. pneumoniae.

    “The elaboration and acquisition of the latter three siderophores are associated with the pathogenesis and hypervirulence of K. pneumoniae (1,44,53,54).”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [1] 1. Holden VI, Bachman MA. 2015. Diverging roles of bacterial siderophores during infection. Metallomics 7:986-995. https://doi.org/10.1039/ C4MT00333K source
    • cites [44] 44. Russo TA, Shon AS, Beanan JM, Olson R, MacDonald U, Pomakov AO, Visitacion MP. 2011. "Hypervirulent K. pneumoniae secretes more and more active iron-acquisition molecules than "classical" K. pneumoniae thereby enhancing its virulence". PLoS One 6:e26734. https://doi.org/10. 1371/journal.pone.0026734 source

      The Results (page unavailable) show that the hypervirulent strain secreted more siderophores than classical strains, and that its conditioned medium enhanced growth; the mouse-infection Results also link that medium to greater metastatic spread. The paper supports an association between iron-acquisition molecules and hypervirulence, but it does not identify or test the specific ‘latter three’ siderophores attributed to it. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [53] 53. Holden VI, Wright MS, Houle S, Collingwood A, Dozois CM, Adams MD, Bachman MA. 2018. Iron acquisition and siderophore release by carbapenem-resistant sequence type 258 Klebsiella pneumoniae. mSphere 3:e00125-18. https://doi.org/10.1128/mSphere.00125-18 source

      The Discussion (page unavailable) says iron acquisition is essential for K. pneumoniae virulence. The Results (page unavailable) also report that salmochelin supports growth in serum, and the References list a study linking yersiniabactin to respiratory infection. Our copy does not establish that elaboration and acquisition of all three siderophores are associated with hypervirulence. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [54] 54. Russo TA, Olson R, MacDonald U, Beanan J, Davidson BA. 2015. Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect Immun 83:3325-3333. https://doi.org/10.1128/IAI.00430-15 source

      The Abstract says hypervirulent K. pneumoniae commonly produces yersiniabactin, salmochelin, and enterobactin, but its experiments found that loss of these siderophores, individually or together, did not decrease virulence in the tested mouse infection models. It identifies aerobactin, rather than the other three, as a major virulence factor. No page number is available in our copy. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    Larger halos generally correlate with slower FeEnt uptake.

    “Larger halos generally correlate with slower FeEnt uptake (32,33).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [32] 32. Annamalai R, Jin B, Cao Z, Newton SMC, Klebba PE. 2004. Recognition of ferric catecholates by FepA. J Bacteriol 186:3578-3589. https://doi.org/ 10.1128/JB.186.11.3578-3589.2004 source
    • cites [33] 33. Cao Z, Qi Z, Sprencel C, Newton SM, Klebba PE. 2000. Aromatic components of two ferric enterobactin binding sites in Escherichia coli FepA. Mol Microbiol 37:1306-1317. https://doi.org/10.1046/j.1365-2958. 2000.02093.x source

      The Transport section (page unavailable) reports larger halos among FepA mutants with transport deficiencies, which supports an association between halo size and impaired FeEnt uptake. It does not establish a general correlation with slower uptake rates: the same section says that only R316A reproducibly reduced the maximum transport rate, and only modestly. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    K. pneumoniae variably produces four siderophores that antagonize host iron sequestration: enterobactin (Ent), glucosylated enterobactin (GEnt; salmochelin), aerobactin (Abn), and yersiniabactin (Ybt).

    “K. pneumoniae variably produces four siderophores that antagonize host iron sequestration: enterobactin (Ent), glucosylated enterobactin (GEnt; also termed salmochelin), aerobactin (Abn), and yersiniabactin (Ybt) (8).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] 8. Russo TA, Olson R, Fang C-T, Stoesser N, Miller M, MacDonald U, Hutson A, Barker JH, La Hoz RM, Johnson JR. 2018. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae. J Clin Microbiol 56:e00776-18. https://doi.org/10.1128/ JCM.00776-18 source

      Materials and Methods (page unavailable) identifies genes for aerobactin, salmochelin, and yersiniabactin biosynthesis, and the Discussion describes aerobactin production by hypervirulent K. pneumoniae. The four siderophores are named together only in a reference title; the paper does not state that K. pneumoniae variably produces all four or that they antagonize host iron sequestration. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Findingcitation

    The consensus Fur recognition sequence motif GATAAT was present in the promoter regions of all the structural genes for these proteins.

    “The consensus Fur recognition sequence motif GATAAT (21,22) was present in the promoter regions of all the structural genes for these proteins, implying their regulation by extracellular iron availability.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [21] 21. Baichoo N, Helmann JD. 2002. Recognition of DNA by Fur: a reinterpreta tion of the Fur box consensus sequence. J Bacteriol 184:5826-5832. https://doi.org/10.1128/JB.184.21.5826-5832.2002 source

      The Results and Discussion identifies GATAAT as a previously proposed Fur-recognition hexamer. But the paper revises that model, proposing a 15-bp inverted heptamer repeat as the core recognition sequence; it does not establish GATAAT as the consensus recognition motif. The citation follows the motif name, so the citing authors’ observation about their genes’ promoters is not assessed here. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [22] 22. Baichoo N, Wang T, Ye R, Helmann JD. 2002. Global analysis of the Bacillus subtilis Fur regulon and the iron starvation stimulon. Mol Microbiol 45:1613-1629. https://doi.org/10.1046/j.1365-2958.2002. 03113.x source
  • Interpretationcitation

    Antibiotics that target TonB-dependent pathways may reduce pathogenesis.

    “Consequently, antibiotics that target TonB-dependent pathways may reduce pathogenesis (10).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] 10. Klebba PE, Newton SMC, Six DA, Kumar A, Yang T, Nairn BL, Munger C, Chakravorty S. 2021. Iron acquisition systems of Gram-negative bacterial pathogens define TonB-dependent pathways to novel antibiotics. Chem Rev 121:5193-5239. https://doi.org/10.1021/acs.chemrev.0c01005 Full-Length Text Journal of Bacteriology May 2024 Volume 206 Issue 5 10.1128/jb.00024-2413 source
  • May combine two claims. 39
  • Classified as probably not a substantial claim. 16

  • May combine two claims.

    Premisecitation

    The elaboration of multiple siderophores promotes colonization of different host tissues and creates iron uptake redundancy that may overcome host neutralization of any particular ferric siderophore.

    “The elaboration of multiple siderophores promotes colonization of different host tissues (1,9) and creates iron uptake redun dancy that may overcome host neutralization of any particular ferric siderophore.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] 1. Holden VI, Bachman MA. 2015. Diverging roles of bacterial siderophores during infection. Metallomics 7:986-995. https://doi.org/10.1039/ C4MT00333K source
    • cites [9] 9. Miethke M, Marahiel MA. 2007. Siderophore-based iron acquisition and pathogen control. Microbiol Mol Biol Rev 71:413-451. https://doi.org/10. 1128/MMBR.00012-07 source

      The citation is attached to the claim about colonizing different host tissues. The Introduction says an arsenal of iron-acquisition systems helps pathogens multiply in different compartments, but it does not specifically establish that producing multiple siderophores promotes that colonization. The subsequent, uncited redundancy claim is not attributed to this source here. (LLM, conf=0.79)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Each KpnFepA contains >50% identity to EcoFepA, ensuring a similar protein fold.

    “However, each of them contains >50% identity to EcoFepA, ensuring a similar protein fold (25,26).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [25] 25. Ginalski K. 2006. Comparative modeling for protein structure prediction. Curr Opin Struct Biol 16:172-177. https://doi.org/10.1016/j.sbi.2006.02. 003 source
    • cites [26] 26. Stokes-Rees I, Sliz P. 2010. Protein structure determination by exhaustive search of protein data bank derived databases. Proc Natl Acad Sci USA 107:21476-21481. https://doi.org/10.1073/pnas.1012095107 source

      The Results describe a related p97 example in which proteins have similar architecture, consistent with the general idea that related sequences can have similar structures. The paper does not discuss KpnFepA or EcoFepA, establish their >50% identity, or show that their folds are similar. (LLM, conf=0.81)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premiseown data

    When expressing an LGP of interest, OKN3 and OKN359 (both tonB+) were capable of ferric catecholate binding and transport; OKN13 (ΔtonB) bound but could not transport iron complexes.

    “When expressing an LGP of interest, OKN3 and OKN359 (both tonB + ) were capable of ferric catecholate binding and transport; OKN13 (ΔtonB), on the other hand, bound but could not transport iron complexes.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [23] 23. Ma L, Kaserer W, Annamalai R, Scott DC, Jin B, Jiang X, Xiao Q, Maymani H, Massis LM, Ferreira LCS, Newton SMC, Klebba PE. 2007. Evidence of ball-and-chain transport of ferric enterobactin through FepA. J Biol Chem 282:397-406. https://doi.org/10.1074/jbc.M605333200 source

      The Results (page unavailable) report that OKN3 expressing FepA bound and transported ferric enterobactin. The Cellular Distribution section (page unavailable) says TonB-deficient cells bind but do not transport it, consistent with the claim about OKN13. The Results identify OKN359 as a constructed deletion strain but do not report its binding or transport when expressing a receptor; the paper also does not establish this behavior for any LGP of interest. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Modification of site-directed Cys substitutions in E. coli LGP Fiu, FepA, and Cir with fluorescein maleimide (FM) facilitated measurement of their binding specificities, affinities for various ligands, and transport properties.

    “For example, modification of site-directed Cys substitutions in the Escherichia coli LGP Fiu, FepA, and Cir with fluorescein maleimide (FM) facilitated the measurement of their binding specificities, affinities for various ligands, and transport properties (16).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] 16. Yang T, Zou Y, Ng HL, Kumar A, Newton SM, Klebba PE. 2024. Specificity and mechanism of TonB-dependent ferric catecholate uptake by Fiu. Front Microbiol 15:1355253. source

      In “Fluorescence spectroscopic measurements of receptor-ligand binding” (page unavailable), the paper describes FM labeling of Cys-substituted Fiu and using fluorescence titrations to measure its ligand-binding affinities. It also reports transport specificities for Fiu, FepA, and Cir, but the supplied passages do not show FM-labeled Cys substitutions in FepA or Cir, and the Fiu affinity measurements were made in the absence of transport. Thus, the claim overextends what the FM method is shown to measure. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Abundant evidence links bacterial iron acquisition to virulence and infectious disease.

    “Finally, abundant evidence links bacterial iron acquisition to virulence and infectious disease (10).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] 10. Klebba PE, Newton SMC, Six DA, Kumar A, Yang T, Nairn BL, Munger C, Chakravorty S. 2021. Iron acquisition systems of Gram-negative bacterial pathogens define TonB-dependent pathways to novel antibiotics. Chem Rev 121:5193-5239. https://doi.org/10.1021/acs.chemrev.0c01005 Full-Length Text Journal of Bacteriology May 2024 Volume 206 Issue 5 10.1128/jb.00024-2413 source

  • May combine two claims.

    Premisecitation

    Native E. coli FepA contains two Cys residues in loop 7 (C487 and C494), which form a disulfide bond that is indispensable to FeEnt uptake: elimination of either or both abrogates FeEnt transport by EcoFepA.

    “Native E. coli FepA contains two Cys residues in loop 7 (L7; C487 and C494), which form a disulfide bond that is indispensable to FeEnt uptake: elimination of either or both C487 and C494 abrogates FeEnt transport by EcoFepA (29,30,34).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [29] 29. Smallwood CR, Jordan L, Trinh V, Schuerch DW, Gala A, Hanson M, Shipelskiy Y, Majumdar A, Newton SMC, Klebba PE. 2014. Concerted loop motion triggers induced fit of FepA to ferric enterobactin. J Gen Physiol 144:71-80. https://doi.org/10.1085/jgp.201311159 source

      The Discussion identifies a single C487–C494 disulfide bond in FepA loop 7. It does not say that the bond is indispensable for FeEnt uptake or report whether eliminating either or both cysteines abrogates transport. The Results examine a different loop-7 substitution, S490C. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [30] 30. Smallwood CR, Marco AG, Xiao Q, Trinh V, Newton SMC, Klebba PE. 2009. Fluoresceination of FepA during colicin B killing: effects of temperature, toxin and TonB. Mol Microbiol 72:1171-1180. https://doi.org/10.1111/j. 1365-2958.2009.06715.x source

      The indexed passages are labeled as a cardiac xenotransplantation section and discuss gene-knockout pigs, not E. coli FepA. Searches for C487/C494, the loop 7 disulfide, and enterobactin uptake returned no passage addressing the claim. The indexed content also does not match the supplied paper title, so this copy cannot verify the attribution. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [34] 34. Majumdar A, Trinh V, Moore KJ, Smallwood CR, Kumar A, Yang T, Scott DC, Long NJ, Newton SM, Klebba PE. 2020. Conformational rearrange ments in the N-domain of Escherichia coli FepA during ferric enterobac tin transport. J Biol Chem 295:4974-4984. https://doi.org/10.1074/jbc.RA119.011850 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The understanding of the uptake pathways for FeEnt and FeGEnt and their degradation products has clinical importance related to their correlations with microbial virulence.

    “Hence, the understanding of the uptake pathways for FeEnt and FeGEnt and their degradation products has clinical importance related to their correlations with microbial virulence (47,48).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [47] 47. Bullen JJ. 1981. The significance of iron in infection. Rev Infect Dis 3:1127-1138. https://doi.org/10.1093/clinids/3.6.1127 source
    • cites [48] 48. Bullen JJ, Rogers HJ, Spalding PB, Ward CG. 2005. Iron and infection: the heart of the matter. FEMS Immunol Med Microbiol 43:325-330. https:// doi.org/10.1016/j.femsim.2004.11.010 source

      Section 3.2 (page not specified in our copy) links bacterial iron acquisition to growth and virulence, and identifies enterobactin as an iron chelator produced by several pathogenic genera. It does not discuss FeEnt or FeGEnt uptake pathways, their degradation products, or correlations between those specific pathways and virulence. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Apart from binding their primary ligand, FeEnt, with high affinity, and its aposiderophore Ent with 100-200-fold lower affinity, KpnFepA_1658, KpnIroN, and KpnFepA_4984 showed different preferences for ferric catecholate complexes and siderophore antibiotics cefiderocol [FeFDC] and FeMB-1.

    “Apart from binding their primary ligand, FeEnt, with high affinity, and its aposiderophore Ent with 100-200-fold lower affinity (38), KpnFepA_1658, KpnIroN, and KpnFepA_4984 showed different preferences for ferric catecholate complexes and siderophore antibiotics cefiderocol [FeFDC (40,41)] and FeMB-1 (42,43):”
    Quote in the paperSubstantial claim4 of 5 sources checked
    • cites [38] 38. Kumar A, Yang T, Chakravorty S, Majumdar A, Nairn BL, Six DA, Marcondes Dos Santos N, Price SL, Lawrenz MB, Actis LA, Marques M, Russo TA, Newton SM, Klebba PE. 2022. Fluorescent sensors of siderophores produced by bacterial pathogens. J Biol Chem 298:101651. https://doi.org/10.1016/j.jbc.2022.101651 source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [40] 40. Ito A, Nishikawa T, Matsumoto S, Yoshizawa H, Sato T, Nakamura R, Tsuji M, Yamano Y. 2016. Siderophore cephalosporin cefiderocol utilizes ferric iron transporter systems for antibacterial activity against Pseudomonas aeruginosa. Antimicrob Agents Chemother 60:7396-7401. https://doi. org/10.1128/AAC.01405-16 source

      Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [41] 41. Wu JY, Srinivas P, Pogue JM. 2020. Cefiderocol: a novel agent for the management of multidrug-resistant Gram-negative organisms. Infect Dis Ther 9:17-40. https://doi.org/10.1007/s40121-020-00286-6 source
    • cites [42] 42. Tomaras AP, Crandon JL, McPherson CJ, Banevicius MA, Finegan SM, Irvine RL, Brown MF, O'Donnell JP, Nicolau DP. 2013. Adaptation-based resistance to siderophore-conjugated antibacterial agents by Pseudomonas aeruginosa. Antimicrob Agents Chemother 57:4197-4207. https://doi.org/10.1128/AAC.00629-13 source

      Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [43] 43. Tomaras AP, Crandon JL, McPherson CJ, Nicolau DP. 2015. Potentiation of antibacterial activity of the MB-1 siderophore-monobactam conjugate using an efflux pump inhibitor. Antimicrob Agents Chemo ther 59:2439-2442. https://doi.org/10.1128/AAC.04172-14 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Kp52.145 harbors plasmid II, a 121.7-kB plasmid that was only found in one other K. pneumoniae strain (B5055).

    “Kp52.145 harbors plasmid II, a 121.7-kB plasmid (57) that was only found in one other K. pneu moniae strain (B5055).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [57] 57. Bialek-Davenet S, Criscuolo A, Ailloud F, Passet V, Jones L, Delannoy- Vieillard AS, Garin B, Le Hello S, Arlet G, Nicolas-Chanoine MH, Decré D, Brisse S. 2014. Genomic definition of hypervirulent and multidrug- resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis 20:1812- 1820. https://doi.org/10.3201/eid2011.140206 source

      The Data Availability section identifies sequences for the CIP 52.145 chromosome and two plasmids, supporting that the strain carries plasmids. Our copy does not identify either as plasmid II, give a size of 121.7 kB, or say it was found only in strain B5055; searches for those terms found no matching passage. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    All these systems are Fur-regulated and activated upon iron deprivation in the host or when grown under pathophysiological conditions.

    “All these systems are Fur-regulated and activated upon iron deprivation in the host (50-52) or when grown under pathophysiological conditions (38).”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [50] 50. Achenbach LA, Yang W. 1997. The Fur gene from Klebsiella pneumoniae: characterization, genomic organization and phylogenetic analysis. Gene 185:201-207. https://doi.org/10.1016/S0378-1119(96)00642-7 source
    • cites [51] 51. Lin CT, Wu CC, Chen YS, Lai YC, Chi C, Lin JC, Chen Y, Peng HL. 2011. Fur regulation of the capsular polysaccharide biosynthesis and iron- acquisition systems in Klebsiella pneumoniae CG43. Microbiology (Reading) 157:419-429. https://doi.org/10.1099/mic.0.044065-0 source
    • cites [52] 52. Yuan L, Li X, Du L, Su K, Zhang J, Liu P, He Q, Zhang Z, Peng D, Shen L, Qiu J, Li Y. 2020. RcsAB and Fur coregulate the iron-acquisition system via entC in Klebsiella pneumoniae NTUH-K2044 in response to iron availability. Front Cell Infect Microbiol 10:282. https://doi.org/10.3389/ fcimb.2020.00282 source

      The Introduction and Discussion report that Fur regulates entC in K. pneumoniae in response to iron availability, with iron-starvation conditions favoring iron-acquisition activity. The paper does not establish that all the systems in the citing sentence are Fur-regulated or that they are activated specifically during iron deprivation in the host. The pathophysiological-conditions clause has a separate citation. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [38] 38. Kumar A, Yang T, Chakravorty S, Majumdar A, Nairn BL, Six DA, Marcondes Dos Santos N, Price SL, Lawrenz MB, Actis LA, Marques M, Russo TA, Newton SM, Klebba PE. 2022. Fluorescent sensors of siderophores produced by bacterial pathogens. J Biol Chem 298:101651. https://doi.org/10.1016/j.jbc.2022.101651 source

      The Abstract (page unavailable) describes bacterial iron acquisition and competition with hosts, and the Experimental procedures describe growth in iron-deficient media. Neither passage says the systems are Fur-regulated or activated under pathophysiological growth conditions; searches for Fur and those conditions found no supporting passage. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    During colonization in human and animal hosts, microbes must acquire iron for growth and proliferation.

    “During the colonization in human and animal hosts, microbes must acquire iron for growth and proliferation (13), and it is noteworthy that K. pneumoniae pro duces several siderophores that promote invasiveness and pathogenesis: aerobactin, yersiniabactin, and the catecholate compound, glucosylated enterobactin.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] 13. Pi H, Jones SA, Mercer LE, Meador JP, Caughron JE, Jordan L, Newton SM, Conway T, Klebba PE. 2012. Role of catecholate siderophores in Gram- negative bacterial colonization of the mouse gut. PLoS One 7:e50020. https://doi.org/10.1371/journal.pone.0050020 source

  • May combine two claims.

    Premisecitation

    Virulent strains encode siderophore biosynthetic operons for the production of Ent, GEnt, Abn, and Ybt and produce cognate receptor LGPs for their OM transport.

    “Virulent strains encode siderophore biosynthetic operons for the production of Ent, GEnt, Abn, and Ybt (1) and produce cognate receptor LGPs for their OM transport [(49); this report].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] 1. Holden VI, Bachman MA. 2015. Diverging roles of bacterial siderophores during infection. Metallomics 7:986-995. https://doi.org/10.1039/ C4MT00333K source
    • cites [49] 49. Klebba PE, Newton SMC, Six DA, Kumar A, Yang T, Nairn BL, Munger C, Chakravorty S. 2021. Iron acquisition systems of Gram (-) bacterial pathogens define TonB-dependent pathways to novel antibiotics. Chem Rev 121:5193-5239. https://doi.org/10.1021/acs.chemrev.0c01005 source

  • May combine two claims.

    Findingcitation

    SCN preferentially blocked the uptake of FeEnt, but not any of the other ferric siderophores.

    “Consistent with their binding affinities for the serum protein [FeGEnt, FeAbn, FeYbr << FeEnt (38)], SCN preferentially blocked the uptake of FeEnt, but not any of the other ferric siderophores (Fig. 4C through F).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [38] 38. Kumar A, Yang T, Chakravorty S, Majumdar A, Nairn BL, Six DA, Marcondes Dos Santos N, Price SL, Lawrenz MB, Actis LA, Marques M, Russo TA, Newton SM, Klebba PE. 2022. Fluorescent sensors of siderophores produced by bacterial pathogens. J Biol Chem 298:101651. https://doi.org/10.1016/j.jbc.2022.101651 source

  • May combine two claims.

    Findingcitation

    Unlike FeEnt, FeAbn uptake was not inhibited by SCN, reinforcing its importance in the pathogenesis of hvKp1.

    “However, unlike FeEnt, FeAbn uptake was not inhibited by SCN, reinforcing its importance in the pathogenesis of hvKp1 (54).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [54] 54. Russo TA, Olson R, MacDonald U, Beanan J, Davidson BA. 2015. Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect Immun 83:3325-3333. https://doi.org/10.1128/IAI.00430-15 source

      The Results passage on growth in ascites fluid and serum, together with the Discussion, supports aerobactin’s importance to hvKP1 under the conditions tested. But our copy does not report that SCN inhibits FeEnt uptake while leaving FeAbn uptake unaffected; searches for SCN, siderocalin, and uptake did not establish that comparison. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    The fluorescent sensors functioned in K. pneumoniae and in TonB-deficient E. coli strain OKN1359, where they bound but did not transport ligands.

    “The fluorescent sensors functioned in K. pneumoniae (i.e., as species-specific sensors) and in the TonB-deficient E. coli strain OKN1359, where they bound but did not transport ligands (i.e., functioned as decoy sensors) (17).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] 17. Chakravorty S, Shipelskiy Y, Kumar A, Majumdar A, Yang T, Nairn BL, Newton SM, Klebba PE. 2019. Universal fluorescent sensors of high- affinity iron transport, applied to ESKAPE pathogens. J Biol Chem 294:4682-4692. https://doi.org/10.1074/jbc.RA118.006921 source

  • May combine two claims.

    Findingown data

    locus 2380 encoded a protein that bound ferric catecholate compounds but did not detectably transport them.

    “locus 2380 encoded a protein that bound ferric catecholate compounds but did not detectably transport them.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    One locus encodes IroN (locus 0027 on plasmid pII), and three other loci encode other FepA orthologs/paralogs (chromosomal loci 1658, 2380, and 4984).

    “One locus encodes IroN (locus 0027 on plasmid pII), and three other loci encode other FepA orthologs/paralogs (chromosomal loci 1658, 2380, and 4984).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    KpnFepA_2380 is 65.9% identical to EcoIroN, which is itself 92% identical to KpnIroN.

    “The most distant chromosomally encoded protein, KpnFepA_2380, is 65.9% identical to EcoIroN (17,20), which is itself 92% identical to KpnIroN.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] 17. Chakravorty S, Shipelskiy Y, Kumar A, Majumdar A, Yang T, Nairn BL, Newton SM, Klebba PE. 2019. Universal fluorescent sensors of high- affinity iron transport, applied to ESKAPE pathogens. J Biol Chem 294:4682-4692. https://doi.org/10.1074/jbc.RA118.006921 source
    • cites [20] 20. Skyberg JA, Johnson TJ, Johnson JR, Clabots C, Logue CM, Nolan LK. 2006. Acquisition of avian pathogenic Escherichia coli plasmids by a commensal E. coli isolate enhances its abilities to kill chicken embryos, grow in human urine, and colonize the murine kidney. Infect Immun 74:6287-6292. https://doi.org/10.1128/IAI.00363-06 source

  • May combine two claims.

    Findingnone given

    The first locus encodes a protein synonymous with IroN, which recognizes and transports FeGEnt.

    “The first locus encodes a protein synonymous with IroN, which recognizes and transports FeGEnt.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    FeEnt binding quenched the fluorescence of most mutant KpnFepA proteins, and fluorescence intensity recovered as the bacteria transported FeEnt and depleted it from the ambient solution.

    “FeEnt binding quenched the fluorescence of most mutant proteins, but fluorescence intensity recovered as the bacteria transported FeEnt and depleted it from the ambient solution,”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Rapid binding of FeEnt, FeAbn, and FeYbt (maximum quenching of their respective sensors within 100 s) was immediately followed by steady uptake by hvKp1, at different rates: FeYbt < FeAbn ≈ FeEnt.

    “Rapid binding of FeEnt, FeAbn, and FeYbt (i.e., maximum quenching of their respective sensors within 100 s) was immediately followed by steady uptake by hvKp1, at different rates: FeYbt < FeAbn ≈ FeEnt.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the presence of hvKp1, FeGEnt adsorbed more slowly (maximum quenching of OKN13/pKpnIroN-T210C-FM at ~500 s) and transported at a much slower rate than FeEnt or FeAbn, roughly equivalent to that of FeYbt.

    “On the other hand, in the presence of hvKp1, FeGEnt adsorbed more slowly (i.e., maximum quenching of OKN13/pKpnIroN-T210C-FM at ~500 s) and transported at a much slower rate than FeEnt or FeAbn, roughly equivalent to that of FeYbt (Fig. 4B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Cys mutants of KpnIroN_0027 behaved nearly identically to those of KpnFepA_1658: 10%-50% quenching by FeEnt and uptake of the ferric siderophore within 15-20 min.

    “The Cys mutants of KpnIroN_0027) behaved nearly identically to those of KpnFepA_1658: we observed 10%-50% quenching by FeEnt and uptake of the ferric siderophore within 15-20 min (Fig. 2) by its fluoresceinated Cys mutants.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Except for A332C, FM modified all KpnFepA_4984 derivatives (S226C, T281C, A390C, T534C, and T703C), but to a lesser extent than observed for the Cys derivatives of EcoFepA_A698C, KpnFepA_1658, and KpnIroN.

    “Except for A332C, FM modified all of its derivatives (S226C, T281C, A390C, T534C, and T703C), but to a lesser extent (Fig. S3) than observed for the Cys derivatives of EcoFepA_A698C, KpnFepA_1658, and KpnIroN.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The Cys mutants of KpnIroN, KpnFepA_1658, and KpnFepA_4984 were susceptible to modification by FM, and their fluorescent derivatives all detected the transport of FeEnt.

    “Nevertheless, together, the results showed that the Cys mutants of KpnIroN, KpnFepA_1658, and KpnFepA_4984 were susceptible to modification by FM, and their fluorescent derivatives all detected the transport of FeEnt.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The assays confirmed the importance of aerobactin production and FeAbn uptake by hvKP1: FeAbn was transported at a rate similar to that of FeEnt, which was considerably faster than the rate of FeYbt transport.

    “Additionally, they confirmed the importance of aerobactin production and FeAbn uptake by hvKP1: it was transported at a rate similar to that of FeEnt, which was considerably faster than the rate of FeYbt transport.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Cys derivatives of KpnIroN bound FeGEnt but did not transport it in E. coli.

    “Additionally, Cys derivatives of KpnIroN bound FeGEnt (Fig. 2) but did not transport it in E. coli because it lacks the periplasmic or components (IroD, IroE) that are needed for FeGEnt uptake.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: E. coli lacks the periplasmic components (IroD, IroE) that are needed for FeGEnt uptake.

  • May combine two claims.

    Findingown data

    KpnFepA_1658 Cys substitution mutants, when expressed in E. coli, had different levels of fluoresceination and different extents of quenching by bound FeEnt, leading to different kinetics of fluorescence recovery as they utilized extracellular FeEnt and depleted it from the cuvette.

    “The Cys substitution mutants of KpnFepA_1658 illustrated the general trends of these experiments: when expressed in E. coli, they had different levels of fluoresceination and different extents of quenching by bound FeEnt, leading to different kinetics of fluorescence recovery as they utilized extracellular FeEnt and depleted it from the cuvette (Fig. 1B and E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    It took longer for the quenched fluorescence of T281C-FM and A390C-FM to rebound to original levels (~30 min), reiterating the slower FeEnt uptake through this receptor that was also observed in siderophore nutrition tests.

    “It also took longer for the quenched fluorescence of T281C-FM and A390C-FM to rebound to original levels (~30 min), reiterating the slower FeEnt uptake through this receptor that we also observed in siderophore nutrition tests.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    KpnFepA_2380 was not well expressed in the E. coli host strain, and its Cys mutants were only weakly labeled by FM.

    “KpnFepA_2380 was not well expressed in the E. coli host strain, and its Cys mutants were only weakly labeled by FM.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    FM did not label wild-type KpnFepA_1658, but it strongly and selectively labeled all the KpnFepA_1658 Cys mutants, to a level comparable to that of EcoFepA_A698C.

    “Like EcoFepA, in the absence of reduction, C482 and C489 were not modified by FM: FM did not label wild-type KpnFepA_1658, but it strongly and selectively labeled all the KpnFepA_1658 Cys mutants, to a level comparable to that of EcoFepA_A698C (Fig. 1; Fig. S1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    In K. pneumoniae host KKN5, three of the Cys derivatives (D273C, A382C, and T693C) were strongly labeled, whereas three others (I218C, A324C, and especially T545C) were less labeled than they were in E. coli.

    “Three of the Cys derivatives (D273C, A382C, and T693C) were strongly labeled, whereas three others (I218C, A324C, and especially T545C) were less labeled than they were in E. coli (Fig. S1B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The assays revealed the unusual uptake kinetics of FeGEnt and the first quantitative description of FeGEnt transport by hypervirulent hypermucoviscous K. pneumoniae.

    “The assays revealed the unusual uptake kinetics of FeGEnt and the first quantitative description of FeGEnt transport by hypervirulent hypermucoviscous K. pneumoniae.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overall, quenching ranged from 5% to 45%, but FeEnt quenched D273C-FM, A382C-FM, and T693C-FM better than I218C-FM, A324C-FM, and T545C-FM.

    “Overall, quenching ranged from 5% to 45%, but FeEnt quenched D273C-FM, A382C-FM, and T693C-FM better than I218C-FM, A324C-FM, and T545C-FM.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In K. pneumoniae KKN5, D273C, A382C, and T693C quenched to greater extents (up to 40%) by FeEnt and acquired FeEnt within 15-20 min.

    “We screened the same FM-labeled Cys mutants in K. pneumoniae KKN5 (Fig. 1C and F; Fig. S1): again, D273C, A382C, and T693C quenched to greater extents (up to 40%) by FeEnt and acquired FeEnt (leading to fluorescence recovery) within 15-20 min.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Each fluorescently labeled Cys mutant had a different initial fluorescence intensity and different extents of quenching in response to FeEnt binding/transport.

    “each of the fluorescently labeled Cys mutants had a different initial intensity and different extents of quenching in response to the binding/transport of FeEnt.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Analysis of quenching of a decoy sensor reveals the concentration of its target ligand in solution, enabling sensitive determinations of the same ligand's uptake by other cells.

    “Analysis of quenching of a decoy sensor reveals the concentration of its target ligand in solution, which enables sensitive determinations of the same ligand's uptake by other cells.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] 17. Chakravorty S, Shipelskiy Y, Kumar A, Majumdar A, Yang T, Nairn BL, Newton SM, Klebba PE. 2019. Universal fluorescent sensors of high- affinity iron transport, applied to ESKAPE pathogens. J Biol Chem 294:4682-4692. https://doi.org/10.1074/jbc.RA118.006921 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    After sequencing their structural genes to validate their construction, siderophore nutrition tests of the mutant receptors expressed in OKN359 were performed.

    “After sequencing their structural genes to validate their construction, we performed siderophore nutrition tests of the mutant receptors, expressed in OKN359 (Fig. S4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a TonB-deficient host, FM-labeled LGP constitutes fluorescent decoy (FD) sensors that adsorb specific ligands but do not transport them.

    “In a TonB-deficient host, FM-labeled LGP constitutes fluorescent decoy (FD) sensors (17) that adsorb specific ligands but do not transport them.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] 17. Chakravorty S, Shipelskiy Y, Kumar A, Majumdar A, Yang T, Nairn BL, Newton SM, Klebba PE. 2019. Universal fluorescent sensors of high- affinity iron transport, applied to ESKAPE pathogens. J Biol Chem 294:4682-4692. https://doi.org/10.1074/jbc.RA118.006921 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    OM ferric siderophore receptors are TonB-dependent members of the porin superfamily, called TonB-dependent transporters or ligand-gated porins.

    “OM ferric siderophore receptors are TonB-dependent members of the porin superfamily.Hence, they are called TonB-dependent transporters (14) or ligand-gated porins [LGP (15)], in the latter case because ligand binding activates their TonB-depend ent transport process.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] 14. Schauer K, Rodionov DA, de Reuse H. 2008. New substrates for TonB- dependent transport: do we only see the 'tip of the iceberg'?Trends Biochem Sci 33:330-338. https://doi.org/10.1016/j.tibs.2008.04.012 source
    • cites [15] 15. Rutz JM, Liu J, Lyons JA, Goranson J, Armstrong SK, McIntosh MA, Feix JB, Klebba PE. 1992. Formation of a gated channel by a ligand-specific transport protein in the bacterial outer membrane. Science 258:471- 475. https://doi.org/10.1126/science.1411544 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    For each data point in the binding assays, quenching determinations were performed in triplicate and mean values with standard deviations were plotted.

    “For each data point, we performed the quenching determinations in triplicate and plotted the mean values with associated standard deviations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    All mutant KpnFepAs were well labeled, with T545C slightly less intensely labeled than the others.

    “All the mutant KpnFepAs were well labeled, T545C slightly less intensely than the others.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The fluorescence intensity of E. coli OKN13/KpnFepA_1658_A382C-FM is inversely related to extracellular [FeEnt], and if the sensor bacteria cohabitate with iron transport-competent bacteria, their fluorescence emissions portray the time-resolved uptake of FeEnt by the other organism.

    “Hence, the fluorescence intensity of the construct E. coli OKN13/ KpnFepA_1658_A382C-FM is inversely related to [FeEnt] extracellular , and if the sensor bacteria cohabitate with iron transport-competent bacteria, then their fluorescence emissions portray the time-resolved uptake of FeEnt by the other organism.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The selectivities of these receptors are relevant to the virulence mechanisms of Gram-negative bacterial ESKAPE pathogens.

    “The selectivities of these receptors are relevant to the virulence mechanisms of Gram-negative bacterial ESKAPE pathogens.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The FeEnt transport experiments were performed in triplicate and average values were plotted.

    “We performed these experiments in triplicate and plotted the average values of the resulting data using Grafit 6.0.12”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Our findings broaden the scope of fluorescence spectroscopic assays by characterizing multiple ferric catecholate receptors in K. pneumoniae that recognize, bind, and transport FeEnt with different affinities.

    “Our findings broaden the scope of fluorescence spectroscopic assays by characterizing multiple ferric catecholate receptors in K. pneumoniae that recognize, bind, and transport FeEnt with different affinities.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    The resultant mutant strain KKN5 did not synthesize Ent and GEnt nor transport ferric catecholates.

    “The resultant mutant strain did not synthesize Ent and GEnt nor transport ferric catecholates.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationown data

    The spectroscopic sensor approaches facilitated observations of the uptake of these ferric siderophores by K. pneumoniae.

    “The spectroscopic sensor approaches we employed facilitated observations of the uptake of these ferric siderophores by K. pneumoniae.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    We validated the construct by Sanger DNA sequencing.

    “We directly used this final product for transformation and validated the construct by Sanger DNA sequencing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    KKN5 was an effective host for plasmids carrying fepA alleles.

    “It was an effective host for plasmids carrying fepA alleles.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    All KpnIroN Cys mutants were well labeled.

    “all the mutants were well labeled.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Each data point in the binding curves represents the mean of triplicate repetitions, with associated standard deviations.

    “Each data point represents the mean of triplicate repetitions, with associated standard deviations.”
    Quote in the paperNot a substantial claim
52 of 52

  • The paper relies on this without support.

    E. coli lacks the periplasmic components (IroD, IroE) that are needed for FeGEnt uptake.

    “Additionally, Cys derivatives of KpnIroN bound FeGEnt (Fig. 2) but did not transport it in E. coli because it lacks the periplasmic or components (IroD, IroE) that are needed for FeGEnt uptake.”

  • The authors state this as an assumption.

    The closely paired Cys residues in predicted L7 of KpnFepA homologs form disulfide bonds.

    “Like EcoFepA, all the KpnFepA homologs contain closely paired Cys residues in predicted L7 that presumably disulfide bonds: 0027 (C475, C484); 1658 (C482, C489); 2380 (C451, C460); 4984 (C490, C497).”

  • The paper relies on this without support.

    Ent production is ubiquitous in both classical and hypervirulent K. pneumoniae, in both the wild and host environments.

    “Ent production is ubiquitous in both classical and hypervirulent K. pneumoniae, in both the wild and host environments.”

  • The paper relies on this without support.

    K. pneumoniae produces several siderophores that promote invasiveness and pathogenesis: aerobactin, yersiniabactin, and glucosylated enterobactin.

    “it is noteworthy that K. pneumoniae pro duces several siderophores that promote invasiveness and pathogenesis: aerobactin, yersiniabactin, and the catecholate compound, glucosylated enterobactin.”

  • The paper relies on this without support.

    Lactone esterases IroD and IroE are absent from the E. coli periplasm.

    “the absence of lactone esterases IroD and IroE from the E. coli periplasm”
5 of 5

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • The residue-703 mutant has conflicting identities

    Minor

    The engineered KpnFepA_4984 mutant is listed as A703C in one section and T703C in another.

  • KKN5 has two different siderophore-biosynthesis deletions

    Minor

    The results identify KKN5 as an entA mutant, while the methods identify the same strain as a ΔentB mutant.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. 10.1021/acs.chemrev.0c01005 · DOI · Paper page

Cited by

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Related

Authors
Kumar, A., Chakravorty, S., Yang, T., Russo, T. A., Newton, S. M., & Klebba, P. E.
Affiliations
  • Kansas State University (US)
  • VA Western New York Healthcare System (US)
ORCID
Venue
Journal of Bacteriology
Publisher
American Society for Microbiology
Published
2024-05-23
Volume
206
Issue
5
Pages
e0002424-e0002424
ISSN
  • 0021-9193 (ISSN-L)
  • 1098-5530
DOI
10.1128/jb.00024-24
PMC
PMC11112993
OpenAlex
W4394621574
Semantic Scholar
5d9d2146a343419248b67c25717323cee68d89dc
Cited by
42
References
61
Citations by year
2026: 23 · 2025: 15 · 2024: 4
FWCI
11.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Bacteriology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • NIH (R21 AI123558-01 and 1R21AI141826-01A1)
  • The Department of Veterans Affairs VA Merit Review (I01 BX004677-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Keywords
siderophore-mediated iron acquisition, Klebsiella pneumoniae, TonB-dependent receptors, iron, catecholate siderophores, outer membrane receptor, crystal structure modeling, hypervirulent Klebsiella pneumoniae
MeSH terms
Bacterial Outer Membrane Proteins, Bacterial Proteins, Biological Transport, Carrier Proteins, Enterobactin, Iron, Klebsiella pneumoniae, Receptors, Cell Surface, Siderophores

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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