Cited by 315Escherichia coli research studiesEnterobacteriaceae and Cronobacter ResearchAntibiotic Resistance in Bacteria

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Aerobactin, but Not Yersiniabactin, Salmochelin, or Enterobactin, Enables the Growth/Survival of Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae Ex Vivo and In Vivo

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Russo, Thomas A., Olson, Ruth, MacDonald, Ulrike, Beanan, Janet, Davidson, Bruce A.·2015·Infection and Immunity

DOI 10.1128/iai.00430-15PMC PMC4496593

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Abstract

The siderophore aerobactin is the dominant siderophore produced by hypervirulent Klebsiella pneumoniae (hvKP) and was previously shown to be a major virulence factor in systemic infection. However, strains of hvKP commonly produce the additional siderophores yersiniabactin, salmochelin, and enterobactin. The roles of these siderophores in hvKP infection have not been optimally defined. To that end, site-specific gene disruptions were created in hvKP1 (wild type), resulting in the generation of hvKP1Δ iucA (aerobactin deficient), hvKP1Δ iroB (salmochelin deficient), hvKP1Δ entB (enterobactin and salmochelin deficient), hvKP1Δ irp2 (yersiniabactin deficient), and hvKP1Δ entB Δ irp2 (enterobactin, salmochelin, and yersiniabactin deficient). The growth/survival of these constructs was compared to that of their wild-type parent hvKP1 ex vivo in human ascites fluid, human serum, and human urine and in vivo in mouse systemic infection and pulmonary challenge models. Interestingly, in contrast to aerobactin, the inability to produce enterobactin, salmochelin, or yersiniabactin individually or in combination did not decrease the ex vivo growth/survival in human ascites or serum or decrease virulence in the in vivo infection models. Surprisingly, none of the siderophores increased growth in human urine. In human ascites fluid supplemented with exogenous siderophores, siderophores increased the growth of hvKP1Δ iucA , with the relative activity being enterobactin > aerobactin > yersiniabactin > salmochelin, suggesting that the contribution of aerobactin to virulence is dependent on both innate biologic activity and quantity produced. Taken together, these data confirm and extend a role for aerobactin as a critical virulence factor for hvKP. Since it appears that aerobactin production is a defining trait of hvKP strains, this factor is a potential antivirulence target.

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Zeng, L., Hu, K., Zheng, Z., Yu, H., Zheng, W. H., Xu, Q., Yan, J., Xiang, M., Wu, J., & Li, J. (2024) · Research Square · doi:10.21203/rs.3.rs-4279248/v1
Characterisation of resistance and hypervirulence-encoding genetic elements in foodborne Klebsiella pneumoniae isolates
Hu, Q., Yang, C., Ye, L., Yang, X., Chan, E. W., & Chen, S. (2025) · EMI Animal & Environment · doi:10.1080/29986990.2025.2525100
IucA gene contributes to the infectivity of hypervirulent Klebsiella pneumoniae in Caco-2 cell modelsPreprint
Zhi, T., Zhu, C., Zi, C., Xie, J., Lao, R., Wang, L., Gao, J.-M., Mi, N., & Zhao, Z. (2025) · Research Square · doi:10.21203/rs.3.rs-7689359/v1
Distinct and shared impacts of virulence plasmids on the phenotype and transcriptome in convergent carbapenem-resistant and hypervirulent Klebsiella pneumoniae
Hao, M., Cui, X., Feng, L., Liu, K., Shi, X., Long, T., Rowe, S. E., Lin, Y.-T., & Chen, L. (2026) · Microbiology Spectrum · doi:10.1128/spectrum.04174-25
“Siderophores increase the ability of hvKp to acquire iron from the host (1), of which aerobactin is the dominant siderophore produced by hvKp (24).”
Features of virulence factors of the Enterobacteriaceae involved in the necrotizing enterocolitis development
Kokorev, D. A., Александровна, С. Е., Кабанова, Н. П., Yankovaya, Z. A., Konstantinov, D. Y., & Lyamin, A. V. (2025) · Meditsinskiy sovet = Medical Council · doi:10.21518/ms2025-348
The dual implications of iron homeostasis as a bacterial threat: its roles in virulence and antimicrobial resistance
Rajasekar, N., Srinivasan, V. B., Krishnan, K., Giri, C., Kumar, M., Singh, B., & Rajamohan, G. (2025) · Archives of Microbiology · doi:10.1007/s00203-025-04594-8
“Similarly, aerobactin is essential for growth and survival in human ascites fluid and serum but not in urine (Russo et al. 2015).”
Additional file 8 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267571
Additional file 1 of ST218 Klebsiella pneumoniae became a high-risk clone for multidrug resistance and hypervirulence
Yang, P., Liu, C., Du, P., Yi, J., Wu, Z., Zheng, J., Shen, N., Cui, L., & Lu, M. (2024) · Figshare · doi:10.6084/m9.figshare.25210613
Additional file 1 of Mobilizable plasmids drive the spread of antimicrobial resistance genes and virulence genes in Klebsiella pneumoniae
Zhang, J., Xu, Y., Wang, M., Li, X., Liu, Z., Kuang, D., Deng, Z., Ou, H.-Y., & Qu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26648274
Additional file 7 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267568
Additional file 1 of Genomic characterization of colistin-resistant Klebsiella pneumoniae isolated from intensive care unit patients in Egypt
Attalla, E. T., Khalil, A. M., Zakaria, A. S., Baker, D., & Mohamed, N. M. (2023) · Figshare · doi:10.6084/m9.figshare.24115065
Additional file 1 of Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia
Guo, M., Gao, B., Su, J., Zeng, Y., Cui, Z., Liu, H., Guo, X., Zhu, Y., Wei, B., Zhao, Y., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24558122
Additional file 2 of Mobilizable plasmids drive the spread of antimicrobial resistance genes and virulence genes in Klebsiella pneumoniae
Zhang, J., Xu, Y., Wang, M., Li, X., Liu, Z., Kuang, D., Deng, Z., Ou, H.-Y., & Qu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26648277
Additional file 6 of Mobilizable plasmids drive the spread of antimicrobial resistance genes and virulence genes in Klebsiella pneumoniae
Zhang, J., Xu, Y., Wang, M., Li, X., Liu, Z., Kuang, D., Deng, Z., Ou, H.-Y., & Qu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26648289
Additional file 1 of Identification of hypervirulent Klebsiella pneumoniae based on biomarkers and Galleria mellonella infection model
Mai, D., Wu, A., Li, R., Cai, D., Tong, H., Wang, N., & Tan, J. (2023) · Figshare · doi:10.6084/m9.figshare.24669815
Additional file 2 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267553
Additional file 1 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267547
Additional file 7 of Mobilizable plasmids drive the spread of antimicrobial resistance genes and virulence genes in Klebsiella pneumoniae
Zhang, J., Xu, Y., Wang, M., Li, X., Liu, Z., Kuang, D., Deng, Z., Ou, H.-Y., & Qu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26648292
Additional file 11 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267264
Additional file 10 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267261
Additional file 5 of Mobilizable plasmids drive the spread of antimicrobial resistance genes and virulence genes in Klebsiella pneumoniae
Zhang, J., Xu, Y., Wang, M., Li, X., Liu, Z., Kuang, D., Deng, Z., Ou, H.-Y., & Qu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26648286
Additional file 2 of Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection
Matono, T., Morita, M., Nakao, N., Teshima, Y., & Ohnishi, M. (2022) · Figshare · doi:10.6084/m9.figshare.19128589
Additional file 1 of Virulence among different types of hypervirulent Klebsiella pneumoniae with multi-locus sequence type (MLST)-11, Serotype K1 or K2 strains
Wang, T.-C., Lin, J.-C., Chang, J.-C., Hiaso, Y.-W., Wang, C.-H., Chiu, S., Fung, C.-P., Chang, F.-Y., & Siu, L.-K. K. (2021) · Figshare · doi:10.6084/m9.figshare.14821210
Additional file 3 of Genomic analysis of the international high-risk clonal lineage Klebsiella pneumoniae sequence type 395
Shaidullina, E., Schwabe, M., Rohde, T., Shapovalova, V. V., Dyachkova, M. S., Дмитриевна, М. А., Savochkina, Y. A., Shelenkov, A. A., Mikhaylova, Y., Sydow, K., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22610633
Additional file 2 of ST218 Klebsiella pneumoniae became a high-risk clone for multidrug resistance and hypervirulence
Yang, P., Liu, C., Du, P., Yi, J., Wu, Z., Zheng, J., Shen, N., Cui, L., & Lu, M. (2024) · Figshare · doi:10.6084/m9.figshare.25210816
Additional file 4 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267559
Additional file 2 of Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia
Guo, M., Gao, B., Su, J., Zeng, Y., Cui, Z., Liu, H., Guo, X., Zhu, Y., Wei, B., Zhao, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.24558216
Additional file 3 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267556
Additional file 6 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267565
Additional file 12 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267267
Additional file 3 of Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia
Guo, M., Gao, B., Su, J., Zeng, Y., Cui, Z., Liu, H., Guo, X., Zhu, Y., Wei, B., Zhao, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26639205
Additional file 3 of Mobilizable plasmids drive the spread of antimicrobial resistance genes and virulence genes in Klebsiella pneumoniae
Zhang, J., Xu, Y., Wang, M., Li, X., Liu, Z., Kuang, D., Deng, Z., Ou, H.-Y., & Qu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26648280
Additional file 4 of Mobilizable plasmids drive the spread of antimicrobial resistance genes and virulence genes in Klebsiella pneumoniae
Zhang, J., Xu, Y., Wang, M., Li, X., Liu, Z., Kuang, D., Deng, Z., Ou, H.-Y., & Qu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26648283
Additional file 2 of Genomic analysis of the international high-risk clonal lineage Klebsiella pneumoniae sequence type 395
Shaidullina, E., Schwabe, M., Rohde, T., Shapovalova, V. V., Dyachkova, M. S., Дмитриевна, М. А., Savochkina, Y. A., Shelenkov, A. A., Mikhaylova, Y., Sydow, K., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22610630
Additional file 1 of Siderophore-harboring gut bacteria and fecal siderophore genes for predicting the responsiveness of fecal microbiota transplantation for active ulcerative colitis
Yan, J., Zhou, G., Ren, R., Zhang, X., Zhang, N., Wang, Z., Peng, L., & Yunsheng, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26738301
Additional file 4 of Genomic analysis of the international high-risk clonal lineage Klebsiella pneumoniae sequence type 395
Shaidullina, E., Schwabe, M., Rohde, T., Shapovalova, V. V., Dyachkova, M. S., Дмитриевна, М. А., Savochkina, Y. A., Shelenkov, A. A., Mikhaylova, Y., Sydow, K., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22610636
Additional file 5 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267562
Additional file 9 of Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates
Kochan, T. J., Nozick, S., Medernach, R. L., Cheung, B. H., Gatesy, S. W. M., Lebrun-Corbin, M., Mitra, S. D., Khalatyan, N., Krapp, F., Qi, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20267574
Emergence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae ST37: genomic and phenotypic characterization of virulence and resistance
Shen, L., Han, W., Huang, Y. L., Wang, S., Gao, H., Yang, J., Fu, J., Chen, Z., Shi, J., Yuan, X., et al. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1741536
Co-evolution of resistance and virulence in Klebsiella pneumoniae liver abscess: PLA-specific mechanisms and therapeutic dilemmas
Lin, H., Huang, Z., & Guo, Y. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1767477
Comparative profiling of virulence determinants, capsular serotypes, and antimicrobial resistance in hypervirulent and classical Klebsiella pneumoniae isolates from liver abscess patients
Liu, J., & Yang, J. (2026) · International Microbiology · doi:10.1007/s10123-026-00804-5
“…demonstrated significantly higher carriage rates of key virulence genes, including rmpA , aerobactin , iutA , magA , wcaG , kfu , allS , peg-344 , and iroB , compared to cKP (Russo et al. 2018, 2015 ; Bialek-Davenet et al. 2013; Yan et al. 2023; Tan et al. 2019; Lin et al. 2014 ; Wei et al. 2016 ).”
Étude des bases moléculaires pour la vectorisation d’antibiotiques permettant de contourner la faible perméabilité des membranes de Pseudomonas aeruginosa
Perraud, Q. (2020) · theses.fr (ABES) · doi:10.70675/108610a4z5659z4807z868bzc3a6a54df844
Heterogeneous carbapenem resistance among carbapenemase-producing Klebsiella pneumoniae
Chiarelli, A. (2021) · theses.fr (ABES) · doi:10.70675/fcc43b7ez6befz4ec3za411z032663f73d20

Authors: Russo, T. A., Olson, R., MacDonald, U., Beanan, J., & Davidson, B. A.
Affiliations: VA Western New York Healthcare System (US)
ORCID: Russo, Thomas A.
MacDonald, Ulrike
Davidson, Bruce A.
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2015-08
Volume: 83
Issue: 8
Pages: 3325-3333
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.00430-15
PMC: PMC4496593
OpenAlex: W2283434174
Semantic Scholar: e716de1372bc2153e94e76130028b8b30a86c6b0
Cited by: 305
References: 49
Citations by year: 2026: 32 · 2025: 32 · 2024: 34 · 2023: 33 · 2022: 56 · 2021: 28 · 2020: 25 · 2019: 16 · 2018: 24 · 2017: 11 · 2016: 13 · 2015: 1
FWCI: 12.66
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs
National Institutes of Health (W81XWH)
National Institute of Allergy and Infectious Diseases (R21AI088318)
Telemedicine and Advanced Technology Research Center
Topics: Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
Life Sciences › Immunology and Microbiology › Microbiology › Enterobacteriaceae and Cronobacter Research
Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
Keywords: aerobactin, yersiniabactin, salmochelin, enterobactin, siderophores, hypervirulent Klebsiella pneumoniae, hypermucoviscous Klebsiella pneumoniae, virulence factors, iron acquisition, iucA, IRP2, entB, iroB, systemic infection, pulmonary infection, ascitic fluid, human serum, human urine
MeSH terms: Animals, Enterobactin, Glucosides, Humans, Hydroxamic Acids, Klebsiella Infections, Klebsiella pneumoniae, Male, Phenols, Thiazoles, Virulence, Siderophores, Microbial Viability, Mice, Young Adult

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Aerobactin, but Not Yersiniabactin, Salmochelin, or Enterobactin, Enables the Growth/Survival of Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae Ex Vivo and In Vivo

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