Non-Replicating Mycobacterium tuberculosis Elicits a Reduced Infectivity Profile with Corresponding Modifications to the Cell Wall and Extracellular Matrix
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A key feature of Mycobacterium tuberculosis is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by M. tuberculosis in the granuloma, and determine the effect of such conditions on the physiology and infectivity of the organism. Non-replicating persistent (NRP) M. tuberculosis was established by the gradual depletion of nutrients in an oxygen-replete and controlled environment. In contrast to rapidly dividing bacilli, NRP bacteria exhibited a distinct phenotype by accumulating an extracellular matrix rich in free mycolate and lipoglycans, with increased arabinosylation. Microarray studies demonstrated a substantial down-regulation of genes involved in energy metabolism in NRP bacteria. Despite this reduction in metabolic activity, cells were still able to infect guinea pigs, but with a delay in the development of disease when compared to exponential phase bacilli. Using these approaches to investigate the interplay between the changing environment of the host and altered physiology of NRP bacteria, this study sheds new light on the conditions that are pertinent to M. tuberculosis dormancy and how this organism could be establishing latent disease.
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EmbR is also phosphorylated by PknH, which is likely present in both growth and stasis on the basis of transcriptional and mutant survival data.
“EmbR is also phosphorylated by PknH86, which is likely present in both growth and stasis on the basis of transcriptional and mutant survival data14,72,81.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [14]
The Discussion ('The composition of extracellular material') reports that pknH is up-regulated in stationary phase, and the Results ('Global gene expression analysis,' Table 2) list it among genes up-regulated in late stationary phase. These transcriptional findings support the stasis portion of the inference, but the cited paper does not establish PknH's presence in both growth and stasis from transcriptional and mutant-survival data. The phosphorylation statement carries a separate citation in the citing sentence. (LLM, conf=0.83)
Experimental — accuracy not yet measuredfbpB expression and fbpA expression increase during growth, resulting in high TDM levels and low levels of free mycolic acids.
“fbpB expression and fbpA expression increase during growth65,106, resulting in high TDM levels and low levels of free mycolic acids14,65,107,108.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [14]
The Results section (‘Re-modeling of the cell wall’; page unavailable) reports that free mycolates increased while TDM decreased as cultures progressed from exponential growth toward non-replication. This supports relatively higher TDM and lower free mycolates at the earlier growth stage. The passages do not establish increased fbpA or fbpB expression or show that their expression caused those lipid levels. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOn entry into stasis, production of TMM and TDM decreases, whereas the levels of free mycolic acids increase and production of mycolylated arabinogalactan keeps pace with the slowed growth rate.
“On entry into stasis, production of TMM and TDM decreases107, whereas the levels of free mycolic acids increase14 and production of mycolylated arabino- galactan keeps pace with the slowed growth rate.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [14]
The Results (‘Re-modeling of the cell wall’; page unavailable) show that TDM and TMM content declined as the cultures entered stationary and non-replicating phases. The cited paper does not establish that their production decreased; the Discussion (‘The composition of extracellular material’) instead raises increased TDM cleavage as a possible explanation. Citation 107 is attached to the TMM/TDM clause, not the later free-mycolic-acid or arabinogalactan claims. (LLM, conf=0.82)
Experimental — accuracy not yet measuredDifferential transcription of arabinotransferases may help keep LAM synthesis high when arabinogalactan synthesis slows on entry into stasis in the chronic phase.
“Differential transcription of these arabinotransferases may help keep LAM synthe- sis high14 when arabinogalactan synthesis slows on entry into stasis in the chronic phase.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [14]
Regulation of the cell wall affects immune responses and determines sensitivity to antibiotics.
“regulation of the cell wall affects immune responses13 (Box 1) and determines sensitivity to antibiotics14–18 (Box 2).”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [14]
As these STPKs are associated with stasis conditions, their phosphorylation of FAS-II enzymes reduces mycolic acid synthesis during stasis and chronic phases of infection.
“As these STPKs are associated with stasis conditions14,72,94,95, we predict that their phosphorylation of FAS-II enzymes reduces mycolic acid synthesis during stasis and chronic phases of infection.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [14]
Through phosphorylation, PknH may substantially downregulate InhA activity in stasis, thus making M. tuberculosis less sensitive to isoniazid, as is observed in starvation.
“through phosphorylation, PknH92 may substantially downregulate inha activity in stasis14, thus making M. tuberculosis less sensitive to isoniazid, as is observed in starvation17.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [14]
Citation 17 is attached to the assertion that starvation makes M. tuberculosis less sensitive to isoniazid. The Discussion section on extended nutrient-depletion describes metabolic changes in nutrient-starved bacilli, but does not address isoniazid sensitivity. Searches for isoniazid and reduced drug susceptibility found no passage establishing that assertion; the PknH and InhA clauses have separate citations. (LLM, conf=0.70)
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Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Bacterial biofilms: from the Natural environment to infectious diseases
Hall‐Stoodley, L., Costerton, J. W., & Stoodley, P. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro821 · Cited by 7,133 · see citing works
Transcriptional Adaptation of <i>Mycobacterium tuberculosis</i> within Macrophages
Schnappinger, D., Ehrt, S., Voskuil, M. I., Liu, Y., Mangan, J. A., Monahan, I. M., Dolganov, G., Efron, B., Butcher, P. D., Nathan, C., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030846 · Cited by 1,420 · see citing works
Betts, J. C., Lukey, P. T., Robb, L. C., McAdam, R. A., & Duncan, K. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02779.x · Cited by 1,395 · see citing works
McKinney, J. D., zu Bentrup, K. H., Muñoz‐Elías, E. J., Miczák, A., Chen, B., Chan, W.-T., Swenson, D. L., Sacchettini, J. C., Jacobs, W. R., & Russell, D. G. (2000) · Nature · doi:10.1038/35021074 · Cited by 1,361 · see citing works
Wayne, L. G., & Hayes, L. G. (1996) · Infection and Immunity · doi:10.1128/iai.64.6.2062-2069.1996 · Cited by 1,141 · see citing works
Park, H., Guinn, K. M., Harrell, M. I., Liao, R., Voskuil, M. I., Tompa, M., Schoolnik, G. K., & Sherman, D. R. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03474.x · Cited by 712 · see citing works
Mycobacterium tuberculosis: success through dormancy
Gengenbacher, M., & Kaufmann, S. H. E. (2012) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2012.00331.x · Cited by 698 · see citing works
Pathway to Synthesis and Processing of Mycolic Acids in Mycobacterium tuberculosis
Takayama, K., Wang, C., & Besra, G. S. (2005) · Clinical Microbiology Reviews · doi:10.1128/cmr.18.1.81-101.2005 · Cited by 657 · see citing works
Self-citationDaniel, J., Maamar, H., Deb, C., Sirakova, T., & Kolattukudy, P. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002093 · Cited by 595 · see citing works
Ojha, A. K., Baughn, A. D., Sambandan, D., Hsu, T., Trivelli, X., Guérardel, Y., Alahari, A., Kremer, L., Jacobs, W. R., & Hatfull, G. F. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06274.x · Cited by 541 · see citing works
The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol
Telenti, A., Philipp, W. J., Sreevatsan, S., Bernasconi, C., Stockbauer, K. E., Wieles, B., Musser, J. M., & Jacobs, W. R. (1997) · Nature Medicine · doi:10.1038/nm0597-567 · Cited by 473 · see citing works
Deb, C., Lee, C., Dubey, V. S., Daniel, J., Abomoelak, B., Sirakova, T. D., Pawar, S., Rogers, L. M., & Kolattukudy, P. E. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006077 · Cited by 443 · see citing works
New insights into the function of granulomas in human tuberculosis
Ulrichs, T., & Kaufmann, S. H. E. (2006) · Journal of Pathology · doi:10.1002/path.1906 · Cited by 421 · see citing works
Wayne, L. G., & Lin, K. Y. (1982) · Infection and Immunity · doi:10.1128/iai.37.3.1042-1049.1982 · Cited by 326 · see citing works
Mishra, A. K., Driessen, N. N., Appelmelk, B. J., & Besra, G. S. (2011) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2011.00276.x · Cited by 295 · see citing works
Self-citationDeletion of Two-Component Regulatory Systems Increases the Virulence of Mycobacterium tuberculosis
Parish, T., Smith, D. A., Kendall, S. L., Casali, N., Bancroft, G. J., & Stoker, N. G. (2003) · Infection and Immunity · doi:10.1128/iai.71.3.1134-1140.2003 · Cited by 293 · see citing works
Mycobacterium tuberculosis and the intimate discourse of a chronic infection
Russell, D. G. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00984.x · Cited by 291 · see citing works
Ortalo-Magné, A., Lemassu, A., Lanéelle, M., Bardou, F., Silve, G., Gounon, P., Marchal, G., & Daffé, M. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.2.456-461.1996 · Cited by 269 · see citing works
Gengenbacher, M., Rao, S. P. S., Pethe, K., & Dick, T. (2009) · Microbiology · doi:10.1099/mic.0.033084-0 · Cited by 261 · see citing works
Biofilm formation in Campylobacter jejuni
Joshua, G. W. P., Guthrie-Irons, C., Karlyshev, A. V., & Wren, B. W. (2006) · Microbiology · doi:10.1099/mic.0.28358-0 · Cited by 260 · see citing works
Savvi, S., Warner, D. F., Kana, B. D., McKinney, J. D., Mizrahi, V., & Dawes, S. S. (2008) · Journal of Bacteriology · doi:10.1128/jb.01767-07 · Cited by 256 · see citing works
Location of Persisting Mycobacteria in a Guinea Pig Model of Tuberculosis Revealed by R207910
Lenaerts, A. J. M., Hoff, D. R., Aly, S., Ehlers, S., Andries, K., Cantarero, L., Orme, I. M., & Basaraba, R. J. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00276-07 · Cited by 255 · see citing works
Unique Transcriptome Signature of Mycobacterium tuberculosis in Pulmonary Tuberculosis
Rachman, H., Strong, M. J., Ulrichs, T., Grode, L., Schuchhardt, J., Mollenkopf, H., Kosmiadi, G., Eisenberg, D., & Kaufmann, S. (2006) · Infection and Immunity · doi:10.1128/iai.74.2.1233-1242.2006 · Cited by 251 · see citing works
Hampshire, T., Soneji, S., Bacon, J., James, B. W., Hinds, J., Laing, K. G., Stabler, R. A., Marsh, P. D., & Butcher, P. D. (2004) · Tuberculosis · doi:10.1016/j.tube.2003.12.010 · Cited by 212 · see citing works
Self-citationKendall, S. L., Withers, M., Soffair, C. N., Moreland, N. J., Gurcha, S. S., Sidders, B. S., Frita, R., ten Bokum, A., Besra, G. S., Lott, J. S., et al. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05827.x · Cited by 212 · see citing works
Self-citationMolecular composition of the outermost capsular material of the tubercle bacillus
Ortalo-Magné, A., Dupont, M.-A., Lemassu, A., Andersen, Å. B., Gounon, P., & Daffé, M. (1995) · Microbiology · doi:10.1099/13500872-141-7-1609 · Cited by 211 · see citing works
Present aspects of bacterial resistance in tuberculosis.
Canetti, G. (1965) · PubMed · doi:10.1164/arrd.1965.92.5.687 · Cited by 211 · see citing works
A Quantitative Study of Gene Regulation Involved in the Immune Response of Anopheline Mosquitoes
Heard, N. A., Holmes, C. C., & Stephens, D. A. (2006) · Journal of the American Statistical Association · doi:10.1198/016214505000000187 · Cited by 206 · see citing works
Mycobacterium tuberculosis Wears What It Eats
Russell, D. G., VanderVen, B. C., Lee, W., Abramovitch, R. B., Kim, M., Homolka, S., Niemann, S., & Rohde, K. H. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.06.002 · Cited by 194 · see citing works
Turner, O. C., Basaraba, R. J., & Orme, I. M. (2003) · Infection and Immunity · doi:10.1128/iai.71.2.864-871.2003 · Cited by 168 · see citing works
Lee, W., Kang, J.-S., Yan, J.-J., Lee, M. S., Jeon, B., Cho, S.-N., & Kim, Y.-J. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002614 · Cited by 160 · see citing works
Sirakova, T. D., Dubey, V. S., Deb, C., Daniel, J., Korotkova, T. A., Abomoelak, B., & Kolattukudy, P. E. (2006) · Microbiology · doi:10.1099/mic.0.28993-0 · Cited by 158 · see citing works
Converse, P. J., Karakousis, P. C., Klinkenberg, L. G., Kesavan, A. K., Ly, L. H., Allen, S. S., Grosset, J. H. E., Jain, S. K., Lamichhane, G., Manabe, Y. C., et al. (2008) · Infection and Immunity · doi:10.1128/iai.01117-08 · Cited by 153 · see citing works
Alderwick, L. J., Radmacher, E., Seidel, M., Gande, R., Hitchen, P. G., Morris, H. R., Dell, A., Sahm, H., Eggeling, L., & Besra, G. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506339200 · Cited by 144 · see citing works
Self-citationStructural features of the exocellular polysaccharides of Mycobacterium tuberculosis
Lemassu, A., & Daffé, M. (1994) · Biochemical Journal · doi:10.1042/bj2970351 · Cited by 143 · see citing works
Molle, V., Kremer, L., Girard-Blanc, C., Besra, G. S., Cozzone, A. J., & Prost, J.-F. (2003) · Biochemistry · doi:10.1021/bi035150b · Cited by 141 · see citing works
Self-citationBacon, J., James, B. W., Wernisch, L., Williams, A., Morley, K. A., Hatch, G. J., Mangan, J. A., Hinds, J., Stoker, N. G., Butcher, P. D., et al. (2004) · Tuberculosis · doi:10.1016/j.tube.2003.12.011 · Cited by 137 · see citing works
Self-citationOjha, A., Trivelli, X., Guérardel, Y., Kremer, L., & Hatfull, G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.112813 · Cited by 130 · see citing works
Papavinasasundaram, K. G., Chan, B. H. Y., Chung, J.-H., Colston, M. J., Davis, E. O., & Av‐Gay, Y. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.16.5751-5760.2005 · Cited by 128 · see citing works
Loebel, R. O., Shorr, E., & Richardson, H. B. (1933) · Journal of Bacteriology · doi:10.1128/jb.26.2.167-200.1933 · Cited by 125 · see citing works
Beste, D. J. V., Bonde, B. K., Hawkins, N. D., Ward, J. L., Beale, M. H., Noack, S., Nöh, K., Kruger, N. J., Ratcliffe, R. G., & McFadden, J. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002091 · Cited by 119 · see citing works
Sharma, K., Gupta, M., Pathak, M., Gupta, N., Koul, A., Sarangi, S., Baweja, R., & Singh, Y. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.8.2936-2944.2006 · Cited by 113 · see citing works
Talaat, A. M., Ward, S. K., Wu, C., Rondon, E., Tavano, C. L., Bannantine, J. P., Lyons, R., & Johnston, S. A. (2007) · Journal of Bacteriology · doi:10.1128/jb.00011-07 · Cited by 100 · see citing works
Karlyshev, A. V., & Wren, B. W. (2001) · Journal of Clinical Microbiology · doi:10.1128/jcm.39.1.279-284.2001 · Cited by 89 · see citing works
Bacon, J., Dover, L. G., Hatch, K. A., Zhang, Y., Gomes, J. M., Kendall, S. L., Wernisch, L., Stoker, N. G., Butcher, P. D., Besra, G. S., et al. (2007) · Microbiology · doi:10.1099/mic.0.2006/004317-0 · Cited by 87 · see citing works
Self-citationHuang, H., Scherman, M. S., D’Haeze, W., Vereecke, D., Holsters, M., Crick, D. C., & McNeil, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504068200 · Cited by 84 · see citing works
Miller, R. M., Tomaras, A. P., Barker, A. P., Voelker, D. R., Chan, E. D., Vasil, A. I., & Vasil, M. L. (2008) · Journal of Bacteriology · doi:10.1128/jb.00129-08 · Cited by 76 · see citing works
Alderwick, L. J., Lloyd, G. S., Ghadbane, H., May, J. W., Bhatt, A., Eggeling, L., Fütterer, K., & Besra, G. S. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1001299 · Cited by 69 · see citing works
Self-citationGolby, P., Hatch, K. A., Bacon, J., Cooney, R. P., Riley, P., Allnutt, J. C., Hinds, J., Nuñez, J., Marsh, P. D., Hewinson, R. G., et al. (2007) · Microbiology · doi:10.1099/mic.0.2007/009894-0 · Cited by 69 · see citing works
Self-citationJankute, M., Grover, S., Rana, A. K., & Besra, G. S. (2011) · Future Microbiology · doi:10.2217/fmb.11.123 · Cited by 67 · see citing works
Self-citationA truncated lipoglycan from mycobacteria with altered immunological properties
Birch, H. L., Alderwick, L. J., Appelmelk, B. J., Maaskant, J. J., Bhatt, A., Singh, A., Nigou, J., Eggeling, L., Geurtsen, J., & Besra, G. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915082107 · Cited by 60 · see citing works
Self-citationChambers, M. A., Williams, A., Gavier‐Widén, D., Whelan, A. O., Hall, G. A., Marsh, P. D., Bloom, B. R., Jacobs, W. R., & Hewinson, R. G. (2000) · Infection and Immunity · doi:10.1128/iai.68.12.7094-7099.2000 · Cited by 55 · see citing works
Self-citationSurvival of mycobacterial species in aerosols generated from artificial saliva
Lever, M. S., Williams, A., & Bennett, A. (2000) · Letters in Applied Microbiology · doi:10.1046/j.1365-2672.2000.00807.x · Cited by 54 · see citing works
Self-citationMajumdar, S. D., Vashist, A., Dhingra, S., Gupta, R., Singh, A., Challu, V. K., Ramanathan, V. D., Kumar, P., & Tyagi, J. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035847 · Cited by 52 · see citing works
Lipoarabinomannan Localization and Abundance during Growth of Mycobacterium smegmatis
Dhiman, R. K., Dinadayala, P., Ryan, G. J., Lenaerts, A. J. M., Schenkel, A. R., & Crick, D. C. (2011) · Journal of Bacteriology · doi:10.1128/jb.05299-11 · Cited by 45 · see citing works
Clark, S. O., Hall, Y., Kelly, D. L. F., Hatch, G. J., & Williams, A. (2011) · Journal of Applied Microbiology · doi:10.1111/j.1365-2672.2011.05069.x · Cited by 44 · see citing works
Self-citationWilliams, A., Davies, A., Marsh, P. D., Chambers, M. A., & Hewinson, R. G. (2000) · Clinical Infectious Diseases · doi:10.1086/313878 · Cited by 44 · see citing works
Self-citationIn Vivo Adaptation of the Wayne Model of Latent Tuberculosis
Woolhiser, L. K., Henao-Tamayo, M. I., Wang, B., Gruppo, V., Belisle, J. T., Lenaerts, A. J. M., Basaraba, R. J., & Orme, I. M. (2007) · Infection and Immunity · doi:10.1128/iai.00918-06 · Cited by 30 · see citing works
Irby, R. B., & Adair, W. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)51035-3 · Cited by 25 · see citing works
Molybdenum enzymes and molybdenum cofactor in mycobacteria
Shi, T., & Xie, J. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23233 · Cited by 22 · see citing works
Mishra, A. K., Alves, J., Krumbach, K., Nigou, J., Castro, A. G., Geurtsen, J., Eggeling, L., Saraiva, M., & Besra, G. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.402396 · Cited by 15 · see citing works
Self-citationContinuous Culture of Mycobacteria
Bacon, J., & Hatch, K. A. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-207-6_10 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
2 of the 65 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [14]Dobson G, Minnikin DE, Minnikin SM, Partlett JH, Goodfellow M, et al.. (1985) Systematic Analysis of Complex Mycobacterial Lipids. London: Academic Press.
- [17]Carl Edward Rasmussen, Christopher KI Williams (2006) Guassian Processes for Machine Learning. Cambridge MA: MIT Press.
Cited by
Sorted by citations
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Dulberger, C. L., Rubin, E. J., & Boutte, C. C. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0273-7 · Cited by 365 · see citing works
Allué‐Guardia, A., García, J. I., & Torrelles, J. B. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.612675 · Cited by 230 · see citing works
Batt, S. M., Minnikin, D. E., & Besra, G. S. (2020) · Biochemical Journal · doi:10.1042/bcj20200194 · Cited by 160 · see citing works
Self-citationMycobacterium tuberculosis MetabolismPreprint
Warner, D. F. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a021121 · Cited by 102 · see citing works
Challenging the Drug-Likeness Dogma for New Drug Discovery in Tuberculosis
Machado, D., Girardini, M., Viveiros, M., & Pieroni, M. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01367 · Cited by 98 · see citing works
Iizasa, E., Chuma, Y., Uematsu, T., Kubota, M., Kawaguchi, H., Umemura, M., Toyonaga, K., Kiyohara, H., Yano, I., Colonna, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22620-3 · Cited by 92 · see citing works
Piccaro, G., Poce, G., Biava, M., Giannoni, F., & Fattorini, L. (2015) · The Journal of Antibiotics · doi:10.1038/ja.2015.52 · Cited by 75 · see citing works
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Batt, S. M., Burke, C., Moorey, A. R., & Besra, G. S. (2020) · The Cell Surface · doi:10.1016/j.tcsw.2020.100044 · Cited by 60 · see citing works
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Lin, W., de Sessions, P. F., Teoh, G. H. K., Mohamed, A. N. N., Zhu, Y. O., Koh, V. H. Q., Ang, M. L. T., Dedon, P. C., Hibberd, M. L., & Alonso, S. (2016) · Infection and Immunity · doi:10.1128/iai.00072-16 · Cited by 55 · see citing works
Iona, E., Pardini, M., Mustazzolu, A., Piccaro, G., Nisini, R., Fattorini, L., & Giannoni, F. (2016) · The Journal of Microbiology · doi:10.1007/s12275-016-6150-4 · Cited by 51 · see citing works
Trehalose Recycling Promotes Energy-Efficient Biosynthesis of the Mycobacterial Cell Envelope
Pohane, A. A., Carr, C. R., Garhyan, J., Swarts, B. M., & Siegrist, M. S. (2021) · mBio · doi:10.1128/mbio.02801-20 · Cited by 40 · see citing works
Knoll, K. E., der Walt, M. M. V., & Loots, D. T. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.02315-21 · Cited by 31 · see citing works
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Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy
Liu, Y., Li, H., Dai, D., He, J., & Liang, Z. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46060348 · Cited by 29 · see citing works
Timofeeva, L. М., Kleshcheva, N. A., Shleeva, M. O., Филатова, М. П., Simonova, Y. A., Ermakov, Y. A., & Kaprelyants, A. S. (2015) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-014-6331-1 · Cited by 29 · see citing works
Epigenetic Phosphorylation Control of Mycobacterium tuberculosis Infection and Persistence
Richard‐Greenblatt, M., & Av‐Gay, Y. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.tbtb2-0005-2015 · Cited by 29 · see citing works
Mycobacterial Membranes as Actionable Targets for Lipid-Centric Therapy in Tuberculosis
Modak, B., Girkar, S., Narayan, R., & Kapoor, S. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01870 · Cited by 27 · see citing works
Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis
Smith, T. M., Youngblom, M. A., Kernien, J. F., Mohamed, M. A., Fry, S. S., Bohr, L. L., Mortimer, T. D., O’Neill, M. B., & Pepperell, C. S. (2022) · eLife · doi:10.7554/elife.78454 · Cited by 26 · see citing works
Effect of Mycobacterium tuberculosis infection on adipocyte physiology
Ayyappan, J. P., Vinnard, C., Subbian, S., & Nagajyothi, J. F. (2017) · Microbes and Infection · doi:10.1016/j.micinf.2017.10.008 · Cited by 26 · see citing works
Dietrich, J., Roy, S., Rosenkrands, I., Lindenstrøm, T., Filskov, J., Rasmussen, E. M., Cassidy, J. P., & Andersen, P. L. (2015) · Infection and Immunity · doi:10.1128/iai.01055-15 · Cited by 22 · see citing works
Effect of Mycolic Acids on Host Immunity and Lipid Metabolism
Wang, H., Liu, D., & Zhou, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010396 · Cited by 22 · see citing works
Wray, R., Herrera, N., Iscla, I., Wang, J., & Blount, P. (2019) · Molecular Microbiology · doi:10.1111/mmi.14325 · Cited by 22 · see citing works
Mycobacterial mycolic acids trigger inhibitory receptor Clec12A to suppress host immune responses
Nishimura, N., Tomiyasu, N., Torigoe, S., Mizuno, S., Fukano, H., Ishikawa, E., Katano, H., Hoshino, Y., Matsuo, K., Takahashi, M., et al. (2022) · Tuberculosis · doi:10.1016/j.tube.2022.102294 · Cited by 20 · see citing works
Metabolomics: A window into the adaptive physiology of Mycobacterium tuberculosis
Eoh, H. (2014) · Tuberculosis · doi:10.1016/j.tube.2014.08.002 · Cited by 19 · see citing works
The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers
Robinson, R., & Huppler, A. R. (2017) · Cytokine · doi:10.1016/j.cyto.2017.05.015 · Cited by 19 · see citing works
Shukla, S., Bhardwaj, N., & Singh, A. K. (2024) · The Microbe · doi:10.1016/j.microb.2024.100189 · Cited by 18 · see citing works
Keating, T., Lethbridge, S., Allnutt, J. C., Hendon-Dunn, C. L., Thomas, S. R., Alderwick, L. J., Taylor, S. C., & Bacon, J. (2021) · The Cell Surface · doi:10.1016/j.tcsw.2021.100065 · Cited by 18 · see citing works
Self-citationSebastian, J., Nair, R. R., Swaminath, S., & Ajitkumar, P. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.554795 · Cited by 17 · see citing works
Mycobacterial biofilms as players in human infections: a review
Niño-Padilla, E. I., Velázquez, C. A., & Garibay‐Escobar, A. (2021) · Biofouling · doi:10.1080/08927014.2021.1925886 · Cited by 17 · see citing works
Agrawal, G. K., Borody, T. J., & Aitken, J. M. (2024) · Digestive Diseases and Sciences · doi:10.1007/s10620-024-08508-4 · Cited by 16 · see citing works
Singh, P., Kumar, S., Maurya, V. K., Mehta, B. K., Ahmad, H., Dwivedi, A. K., Chaturvedi, V., Thakur, T. S., & Sinha, S. K. (2017) · ACS Omega · doi:10.1021/acsomega.7b01281 · Cited by 16 · see citing works
Role of Chemical Biology in Tuberculosis Drug Discovery and Diagnosis
Kolbe, K., Veleti, S. K., Johnson, E. E., Cho, Y., Oh, S., & Barry, C. E. (2018) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.7b00242 · Cited by 15 · see citing works
Human mesenchymal stem cell based intracellular dormancy model of Mycobacterium tuberculosis
Singh, V. K., Mishra, A., Bark, S. J., Mani, A., Subbian, S., Hunter, R. L., Jagannath, C., & Khan, A. (2020) · Microbes and Infection · doi:10.1016/j.micinf.2020.05.015 · Cited by 15 · see citing works
Modern Anti-Tuberculosis Drugs and Their Classification. Part I: First-Line Drugs
Kаyukova, L. A., & Berikova, E. A. (2020) · Pharmaceutical Chemistry Journal · doi:10.1007/s11094-020-02239-2 · Cited by 13 · see citing works
Stokas, H., Rhodes, H. L., & Purdy, G. E. (2020) · Tuberculosis · doi:10.1016/j.tube.2020.102007 · Cited by 13 · see citing works
Wang, H., Conover, G. M., Han, S., Sacchettini, J. C., & Han, A. (2021) · Microsystems & Nanoengineering · doi:10.1038/s41378-021-00262-1 · Cited by 13 · see citing works
Adjuvant effect in aquaculture fish of cell-wall glycolipids isolated from acid-fast bacteria
Matsumoto, M., Araki, K., Nishimura, S., Kuriyama, H., Nakanishi, T., Shiozaki, K., Takeuchi, Y., & Yamamoto, A. (2018) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2018.04.012 · Cited by 12 · see citing works
Cui, Y., Lanne, A., Peng, X., Browne, E., Bhatt, A., Coltman, N. J., Craven, P. G. E., Cox, L. R., Cundy, N. J., Dale, K., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01643 · Cited by 11 · see citing works
Self-citationMedina‐Alarcón, K. P., da Silva, I. P. T., Ferin, G. G., Pereira-da-Silva, M. A., Marcos, C. M., dos Santos, M. B., Regasini, L. O., Chorilli, M., Mendes‐Giannini, M. J. S., Pavan, F. R., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.681131 · Cited by 11 · see citing works
Drapal, M., Wheeler, P. R., & Fraser, P. D. (2016) · Microbiology · doi:10.1099/mic.0.000325 · Cited by 11 · see citing works
Proteomic characterization of Mycobacterium tuberculosis subjected to carbon starvation
Devlin, K. L., Leach, D. T., Stratton, K. G., Lamichhane, G., Lin, V., & Beatty, K. E. (2025) · mSystems · doi:10.1128/msystems.01530-24 · Cited by 10 · see citing works
Baghdasaryan, O., Contreras-Llano, L. E., Khan, S. A., Wang, A., Hu, C. J., & Tan, C. (2024) · Nature Protocols · doi:10.1038/s41596-024-01035-6 · Cited by 9 · see citing works
Angara, R. K., Yousuf, S., Gupta, S. K., & Ranjan, A. (2017) · Tuberculosis · doi:10.1016/j.tube.2017.10.009 · Cited by 9 · see citing works
Allué‐Guardia, A., Garcia‐Vilanova, A., Olmo-Fontánez, A. M., Peters, J. I., Maselli, D. J., Wang, Y., Turner, J., Schlesinger, L. S., & Torrelles, J. B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020983 · Cited by 9 · see citing works
Optimisation of Mycobacterium bovis BCG Fermentation and Storage Survival
Pascoe, J., Hendon-Dunn, C. L., Birch, C., Williams, G., Chambers, M. A., & Bacon, J. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12090900 · Cited by 7 · see citing works
Self-citationFu, X., Wan, X., Memon, A. A., Fan, X., Sun, Q., Chen, H., Yao, Y., Deng, Z., Ma, J., & Ma, W. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1415554 · Cited by 6 · see citing works
Antituberculosis agents: Beyond medicinal chemistry rules
Pieroni, M. (2019) · Annual reports in medicinal chemistry · doi:10.1016/bs.armc.2019.06.001 · Cited by 6 · see citing works
Sebastian, J., Swaminath, S., & Ajitkumar, P. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/624569 · Cited by 6 · see citing works
Yimcharoen, M., Saikaew, S., Wattananandkul, U., Phunpae, P., Intorasoot, S., Tayapiwatana, C., & Butr-Indr, B. (2023) · Antibiotics · doi:10.3390/antibiotics12050852 · Cited by 5 · see citing works
Host–pathogen interactions in the context of tuberculosis infection and disease
Goletti, D., Aiello, A., Tientcheu, L. D., Muefong, C. N., Hu, T. H., Niewold, P., Joosten, S. A., Ong, C. W. M., & Sutherland, J. S. (2023) · European Respiratory Society eBooks · doi:10.1183/2312508x.10024022 · Cited by 5 · see citing works
Cell Wall Biosynthesis and Latency During Tuberculosis Infections
Kurosu, M. (2019) · Springer eBooks · doi:10.1007/978-3-030-25381-3_1 · Cited by 4 · see citing works
Binnebose, A. M., Mullis, A. S., Haughney, S. L., Narasimhan, B., & Bellaire, B. H. (2023) · Frontiers in Antibiotics · doi:10.3389/frabi.2023.1162941 · Cited by 4 · see citing works
Niño-Padilla, E. I., Espitia, C., Velázquez, C. A., Alday, E., Silva‐Campa, E., Burgara-Estrella, A., Enciso‐Moreno, J. A., Valenzuela, O., Astiazarán‐García, H., & Garibay‐Escobar, A. (2023) · ACS Omega · doi:10.1021/acsomega.3c05703 · Cited by 4 · see citing works
Cholesterol-dependent activity of dapsone against non-replicating persistent mycobacteria
Gibson, S. E. R., Harrison, J., Molloy, A., & Cox, J. A. G. (2022) · Microbiology · doi:10.1099/mic.0.001279 · Cited by 4 · see citing works
Liu, R., Dang, J. N., Lee, R.-E., Lee, J. J., Kesavamoorthy, N., Ameri, H., Rao, N. A., & Eoh, H. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.00788-24 · Cited by 3 · see citing works
Persistent Mycobacterium bovis -BCG is resistant to glutathione induced reductive stress killing
Patel, N., Lawrence, R., & Peteroy-Kelly, M. A. (2016) · Microbial Pathogenesis · doi:10.1016/j.micpath.2016.03.004 · Cited by 3 · see citing works
Farnia, P., Velayati, A. A., Ghanavi, J., & Farnia, P. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-96883-9_7 · Cited by 2 · see citing works
A Mycobacteria-Specific Prodrug to Overcome Phenotypic AMR in Mycobacterium tuberculosis
Kumar, T. A., Birua, S., Mallojjala, S. C., Mukherjee, P., Singh, S., Kaul, G., Ramachandran, A., Akhir, A., Chopra, S., Gadgil, C. J., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01848 · Cited by 2 · see citing works
Gupta, R. K. (2015) · International Journal of Respiratory and Pulmonary Medicine · doi:10.23937/2378-3516/1410025 · Cited by 2 · see citing works
Mycobacterial biofilm: Structure and its functional relevance in the pathogenesis
Behura, A., Das, M., Kumar, A., Naik, L., Patel, S., Nayak, D. K., Mishra, A., Mishra, A., & Dhiman, R. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99977-9.00018-1 · Cited by 2 · see citing works
Shifting Mycobacterial Serine Hydrolase Activity Visualized Using Multi-Layer In-Gel Activity Assays
Goss, A. L., Shudick, R. E., & Johnson, R. J. (2024) · Molecules · doi:10.3390/molecules29143386 · Cited by 1 · see citing works
Poddar, K., Tripathi, G., Khairnar, S. V., Srivastav, S., & Anand, A. (2026) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.6c00483 · Cited by 1 · see citing works
Jazmín, P. (2014) · Mycobacterial Diseases · doi:10.4172/2161-1068.1000e126 · Cited by 1 · see citing works
Epigenetic Phosphorylation Control ofMycobacterium tuberculosisInfection and Persistence
Richard‐Greenblatt, M., & Av‐Gay, Y. (2017) · ASM Press eBooks · doi:10.1128/9781555819569.ch26 · Cited by 1 · see citing works
Multifaceted roles of mycobacterium cell envelope glycolipids during host cell membrane interactions
Mishra, M., & Kapoor, S. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91948-7.00004-x
Contingencies in biofilm adaptation of Mycobacterium tuberculosisPreprint
Kernien, J. F., Youngblom, M. A., Smith, T. M., Fry, S. S., Mohamed, M. A., Murray, H. J., Lawrence, K. N., & Pepperell, C. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.07.597933
The case for developing β-lactam drugs to treat Mycobacterium tuberculosis infections
de Munnik, M., & Schofield, C. J. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00061-3
Dormant yet dangerous: the role of cell rest in perseverance
Bocca, A. L., Trindade, G. B., Souza, R. L., & Fernandes, L. (2025) · Future Microbiology · doi:10.1080/17460913.2025.2599700
Sau, S., Agnivesh, P. K., Roy, A., Kumar, S., & Kalia, N. P. (2026) · Archives of Microbiology · doi:10.1007/s00203-026-04936-0
Adapting Architecture: Lipid Membrane Remodeling in Mycobacteria
Sakarin, I., Maceren, J. P., & Seeliger, J. C. (2026) · Annual Review of Microbiology · doi:10.1146/annurev-micro-042424-042401
- Authors
- Bacon, J., Alderwick, L. J., Allnutt, J. A., Gabasova, E., Watson, R., Hatch, K. A., Clark, S. O., Jeeves, R. E., Marriott, A., Rayner, E., Tolley, H., Pearson, G., Hall, G., Besra, G. S., Wernisch, L., Williams, A., & Marsh, P. D.
- Affiliations
- Public Health England (GB)
- University of Birmingham (GB)
- MRC Biostatistics Unit (GB)
- Corresponding author
- Bacon, Joanna
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-02-06
- Volume
- 9
- Issue
- 2
- Pages
- e87329
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3916317
- OpenAlex
- W2069913108
- Cited by
- 74
- References
- 65
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 3
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Funders
- National Institute for Health and Care Research
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- Mycobacterium tuberculosis, bacterial dormancy, latent tuberculosis infection, extracellular matrix, lipoglycans, cell wall remodeling, infectivity, guinea pig infection model, nutrient depletion
- MeSH terms
- Adaptation, Physiological, Animals, Carbohydrates, Carbon, Cell Wall, Chromatography, Thin Layer, Electrophoresis, Polyacrylamide Gel, Extracellular Matrix, Multigene Family, Guinea Pigs, Mycobacterium Infections, Mycobacterium tuberculosis, Polysorbates, Up-Regulation, Gene Expression Regulation, Bacterial, Gene Expression Profiling, Mice, Bacterial Load, Molecular Sequence Annotation
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