De novo histidine biosynthesis protects Mycobacterium tuberculosis from host IFN-γ mediated histidine starvation.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
25 03 2021
25 03 2021
Historique:
received:
20
03
2020
accepted:
01
03
2021
entrez:
26
3
2021
pubmed:
27
3
2021
medline:
7
8
2021
Statut:
epublish
Résumé
Intracellular pathogens including Mycobacterium tuberculosis (Mtb) have evolved with strategies to uptake amino acids from host cells to fulfil their metabolic requirements. However, Mtb also possesses de novo biosynthesis pathways for all the amino acids. This raises a pertinent question- how does Mtb meet its histidine requirements within an in vivo infection setting? Here, we present a mechanism in which the host, by up-regulating its histidine catabolizing enzymes through interferon gamma (IFN-γ) mediated signalling, exerts an immune response directed at starving the bacillus of intracellular free histidine. However, the wild-type Mtb evades this host immune response by biosynthesizing histidine de novo, whereas a histidine auxotroph fails to multiply. Notably, in an IFN-γ
Identifiants
pubmed: 33767335
doi: 10.1038/s42003-021-01926-4
pii: 10.1038/s42003-021-01926-4
pmc: PMC7994828
doi:
Substances chimiques
Histidine
4QD397987E
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
410Références
AlMatar, M., Makky, E. A., Var, I., Kayar, B. & Köksal, F. Novel compounds targeting InhA for TB therapy. Pharmacol. Rep. 70, 217–226 (2018).
pubmed: 29475004
doi: 10.1016/j.pharep.2017.09.001
Velayati, A. A. et al. Totally drug-resistant tuberculosis strains: Evidence of adaptation at the cellular level. Eur. Respir. J. 34, 1202–1203 (2009).
pubmed: 19880622
doi: 10.1183/09031936.00081909
Kimerling, M. E. et al. Inadequacy of the current WHO re-treatment regimen in a central Siberian prison: treatment failure and MDR-TB. Int. J. Tuberc. Lung Dis. 3, 451–453 (1999).
pubmed: 10331736
Al-Younes, H. M., Gussmann, J., Braun, P. R., Brinkmann, V. & Meyer, T. F. Naturally occurring amino acids differentially influence the development of Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae. J. Med. Microbiol. 55, 879–886 (2006).
pubmed: 16772415
doi: 10.1099/jmm.0.46445-0
Westrop, G. D. et al. Metabolomic analyses of Leishmania reveal multiple species differences and large differences in Amino Acid Metabolism. PLoS ONE 10, 1–29 (2015).
doi: 10.1371/journal.pone.0136891
Zhang, Y. J. et al. Tryptophan biosynthesis protects mycobacteria from CD4 T-Cell-mediated Killing. Cell 155, 1296–1308 (2013).
pubmed: 24315099
pmcid: 3902092
doi: 10.1016/j.cell.2013.10.045
Cole, S. T. et al. Deciphering the biology of mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544 (1998).
pubmed: 9634230
doi: 10.1038/31159
Berney, M. et al. Essential roles of methionine and S-adenosylmethionine in the autarkic lifestyle of Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 112, 10008–10013 (2015).
pubmed: 26221021
doi: 10.1073/pnas.1513033112
pmcid: 4538671
Lunardi, J. et al. Targeting the histidine pathway in Mycobacterium tuberculosis. Curr. Top. Med. Chem. 13, 2866–2884 (2013).
pubmed: 24111909
doi: 10.2174/15680266113136660203
Ahangar, M. S., Vyas, R., Nasir, N. & Biswal, B. K. Structures of native, substrate-bound and inhibited forms of Mycobacterium tuberculosis imidazoleglycerol-phosphate dehydratase. Acta Crystallogr. Sect. D Biol. Crystallogr. 69, 2461–2467 (2013).
doi: 10.1107/S0907444913022579
DeJesus, M. A. et al. Bayesian analysis of gene essentiality based on sequencing of transposon insertion libraries. Bioinformatics 29, 695–703 (2013).
pubmed: 23361328
pmcid: 3597147
doi: 10.1093/bioinformatics/btt043
Wellington, S. et al. Asmall-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase. Nat. Chem. Biol. 13, 943–950 (2017).
pubmed: 28671682
pmcid: 6886523
doi: 10.1038/nchembio.2420
Kohen, R., Yamamoto, Y., Cundy, K. C. & Ames, B. N. Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proc. Natl Acad. Sci. USA 85, 3175–3179 (1988).
pubmed: 3362866
doi: 10.1073/pnas.85.9.3175
pmcid: 280166
Jackson, I. M. D., Ampola, M. G. & Reichlin, S. Hypothalamic and brain thyrotropin-releasing hormone content and pituitary-thyroid function in histidine-deficient rats. Endocrinology 101, 442–446 (1977).
pubmed: 407070
doi: 10.1210/endo-101-2-442
Liao, S. M., Du, Q. S., Meng, J. Z., Pang, Z. W. & Huang, R. B. The multiple roles of histidine in protein interactions. Chem. Cent. J. 7, 44 (2013).
Monti, S. M., De Simone, G. & D’Ambrosio, K. L-histidinol dehydrogenase as a new target for old diseases. Curr. Top. Med. Chem. 16, 2369–2378 (2016).
pubmed: 27072690
doi: 10.2174/1568026616666160413140000
Alifano, P. et al. Histidine biosynthetic pathway and genes: structure, regulation, and evolution. Microbiol. Rev. 60, 44–69 (1996).
pubmed: 8852895
pmcid: 239417
doi: 10.1128/mr.60.1.44-69.1996
Parish, T. Starvation survival response of Mycobacterium tuberculosis. J. Bacteriol. 185, 6702–6706 (2003).
pubmed: 14594845
pmcid: 262115
doi: 10.1128/JB.185.22.6702-6706.2003
Parish, T. et al. Production of mutants in amino acid biosynthesis genes of Mycobacterium tuberculosis by homologous recombination. Microbiology 145, 3497–3503 (1999).
pubmed: 10627047
doi: 10.1099/00221287-145-12-3497
Takach, E., O’Shea, T. & Liu, H. High-throughput quantitation of amino acids in rat and mouse biological matrices using stable isotope labeling and UPLC-MS/MS analysis. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 964, 180–190 (2014).
doi: 10.1016/j.jchromb.2014.04.043
Hu, H. et al. A genetically encoded toolkit for tracking live-cell histidine dynamics in space and time. Sci. Rep. 7, 43479 (2017).
Borah, K. et al. Intracellular Mycobacterium tuberculosis exploits multiple host nitrogen sources during growth in human macrophages. Cell Rep. 29, 3580–3591 (2019).
pubmed: 31825837
pmcid: 6915324
doi: 10.1016/j.celrep.2019.11.037
Gouzy, A., Poquet, Y. & Neyrolles, O. Amino acid capture and utilization within the Mycobacterium tuberculosis phagosome. Future Microbiol. 9, 631–637 (2014).
pubmed: 24957090
doi: 10.2217/fmb.14.28
Agüero, F. et al. Genomic-scale prioritization of drug targets: the TDR targets database. Nat. Rev. Drug Discov. 7, 900–907 (2008).
pubmed: 18927591
pmcid: 3184002
doi: 10.1038/nrd2684
Jha, B. et al. Identification and structural characterization of a histidinol phosphate phosphatase from Mycobacterium tuberculosis. J. Biol. Chem. 293, 10101–10118 (2018).
doi: 10.1074/jbc.RA118.002299
Movahedzadeh, F. et al. Inositol monophosphate phosphatase genes of Mycobacterium tuberculosis. BMC Microbiol. 10, 1–15 (2010).
doi: 10.1186/1471-2180-10-50
Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y. & Morishima, K. KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 45, D353–D361 (2017).
pubmed: 27899662
doi: 10.1093/nar/gkw1092
Hug, D. H., Roth, D. & Hunter, J. Regulation of histidine catabolism by succinate in Pseudomonas putida. J. Bacteriol. 96, 396–402 (1968).
pubmed: 5674054
pmcid: 252311
doi: 10.1128/jb.96.2.396-402.1968
Hirasawa, N. Expression of histidine decarboxylase and its roles in inflammation. Int. J. Mol. Sci. 20, 376 (2019).
Wu, X., Yoshida, A., Sasano, T., Iwakura, Y. & Endo, Y. Histamine production via mast cell-independent induction of histidine decarboxylase in response to lipopolysaccharide and interleukin-1. Int. Immunopharmacol. 4, 513–520 (2004).
pubmed: 15099528
doi: 10.1016/j.intimp.2003.10.011
Urdahl, K. B., Shafiani, S. & Ernst, J. D. Initiation and regulation of T-cell responses in tuberculosis. Mucosal Immunol. 4, 288–293 (2011).
pubmed: 21451503
pmcid: 3206635
doi: 10.1038/mi.2011.10
Wolf, A. J. et al. Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs. J. Exp. Med. 205, 105–115 (2008).
pubmed: 18158321
pmcid: 2234384
doi: 10.1084/jem.20071367
Chen, S., Zhou, Y., Chen, Y. & Gu, J. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34, i884–i890 (2018).
pubmed: 30423086
pmcid: 6129281
doi: 10.1093/bioinformatics/bty560
Ewels, P., Magnusson, M., Lundin, S. & Käller, M. MultiQC: Summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32, 3047–3048 (2016).
pubmed: 27312411
pmcid: 5039924
doi: 10.1093/bioinformatics/btw354
Pertea, M., Kim, D., Pertea, G. M., Leek, J. T. & Salzberg, S. L. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat. Protoc. 11, 1650–1667 (2016).
pubmed: 27560171
pmcid: 5032908
doi: 10.1038/nprot.2016.095
Liao, Y., Smyth, G. K. & Shi, W. FeatureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
doi: 10.1093/bioinformatics/btt656
pubmed: 24227677
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Shannon, P. et al. Cytoscape: a software Environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).
pubmed: 14597658
pmcid: 403769
doi: 10.1101/gr.1239303
Demchak, B. et al. Cytoscape: the network visualization tool for GenomeSpace workflows. F1000Research 3, 151 (2014).
Arakelyan, A. & Nersisyan, L. KEGGParser: parsing and editing KEGG pathway maps in Matlab. Bioinformatics 29, 518–519 (2013).
pubmed: 23292739
doi: 10.1093/bioinformatics/bts730
Nishida, K., Ono, K., Kanaya, S. & Takahashi, K. KEGGscape: a Cytoscape app for pathway data integration. F1000Research 3, 144 (2014).
Wu, G., Dawson, E., Duong, A., Haw, R. & Stein, L. ReactomeFIViz: the Reactome FI Cytoscape app for pathway and network-based data analysis. F1000Research 3, 146 (2014).
pubmed: 25309732
pmcid: 4184317
Bindea, G. et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25, 1091–1093 (2009).
pubmed: 19237447
pmcid: 2666812
doi: 10.1093/bioinformatics/btp101
Kutmon, M., Lotia, S., Evelo, C. T. & Pico, A. R. WikiPathways App for Cytoscape: making biological pathways amenable to network analysis and visualization. F1000Research 3, 152 (2014).
Appelberg, R. Protective role of interferon gamma, tumor necrosis factor alpha and interleukin-6 in Mycobacterium tuberculosis and M. avium infections. Immunobiology 191, 520–525 (1994).
pubmed: 7713566
doi: 10.1016/S0171-2985(11)80458-4
Chernousova, L. N., Smirnova, T. G., Afanasieva, E. G., Karpov, V. L. & Timofeev, A. V. Ex vivo production of interferon-γ, tumor necrosis factor-α, and interleukin-6 by mouse macrophages during infection with M. bovis and M. tuberculosis H37Rv. Bull. Exp. Biol. Med. 144, 709–712 (2007).
pubmed: 18683503
doi: 10.1007/s10517-007-0412-4
Neurath, M. F. & Finotto, S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev. 22, 83–89 (2011).
pubmed: 21377916
doi: 10.1016/j.cytogfr.2011.02.003
Bermudez, L. E. Potential role of cytokines in disseminated mycobacterial infections. Eur. J. Clin. Microbiol. Infect. Dis. 13, S29–33 (1994).
Biondillo, D. E., Konicek, S. A. & Iwamoto, G. K. Interferon-γ regulation of interleukin 6 in monocytic cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 267, L564–8 (1994).
Lazear, H. M. et al. IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling. PLoS Pathog. 9, e1003118 (2013).
Honda, K. et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434, 772–777 (2005).
pubmed: 15800576
doi: 10.1038/nature03464
Sato, M. et al. Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7. FEBS Lett. 441, 106–110 (1998).
pubmed: 9877175
doi: 10.1016/S0014-5793(98)01514-2
Colonna, M. TLR pathways and IFN-regulatory factors: To each its own. Eur. J. Immunol. 37, 306–309 (2007).
pubmed: 17273997
doi: 10.1002/eji.200637009
Rusinova, I. et al. INTERFEROME v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Res. 41, 1040–1046 (2013).
doi: 10.1093/nar/gks1215
Montojo, J. et al. GeneMANIA cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics 26, 2927–2928 (2010).
pubmed: 20926419
pmcid: 2971582
doi: 10.1093/bioinformatics/btq562
Montojo, J., Zuberi, K., Rodriguez, H., Bader, G. D. & Morris, Q. GeneMANIA: fast gene network construction and function prediction for Cytoscape. F1000Research 3, 153 (2014).
Van Landeghem, S., Van Parys, T., Dubois, M., Inzé, D. & Van De Peer, Y. Diffany: an ontology-driven framework to infer, visualise and analyse differential molecular networks. BMC Bioinformatics 17, 18 (2016).
Qing, Y. & Stark, G. R. Alternative activation of STAT1 and STAT3 in response to interferon-γ. J. Biol. Chem. 279, 41679–41685 (2004).
pubmed: 15284232
doi: 10.1074/jbc.M406413200
Mogensen, T. H. IRF and STAT transcription factors - from basic biology to roles in infection, protective immunity, and primary immunodeficiencies. Front. Immunol. 10, 1–13 (2019).
Wan, C. K. et al. Opposing roles of STAT1 and STAT3 in IL-21 function in CD4+ T cells. Proc. Natl Acad. Sci. USA 112, 9394–9399 (2015).
pubmed: 26170288
doi: 10.1073/pnas.1511711112
pmcid: 4522759
Sugawara, I., Yamada, H. & Mizuno, S. STAT1 knockout mice are highly susceptible to pulmonary mycobacterial infection. Tohoku J. Exp. Med. 202, 41–50 (2004).
pubmed: 14738323
doi: 10.1620/tjem.202.41
Gabay, C. Interleukin-6 and chronic inflammation. Arthritis Res. Ther. 8, S3 (2006).
Green, A. M., DiFazio, R. & Flynn, J. L. IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection. J. Immunol. 190, 270–277 (2013).
pubmed: 23233724
doi: 10.4049/jimmunol.1200061
Flynn, J. A. L. Lessons from experimental Mycobacterium tuberculosis infections. Microbes Infect. 8, 1179–1188 (2006).
pubmed: 16513383
doi: 10.1016/j.micinf.2005.10.033
Queval, C. J., Brosch, R. & Simeone, R. The macrophage: a disputed fortress in the battle against Mycobacterium tuberculosis. Front. Microbiol. 8, 2284 (2017).
Jamwal, S. V. et al. Mycobacterial escape from macrophage phagosomes to the cytoplasm represents an alternate adaptation mechanism. Sci. Rep. 6, 23089 (2016).
Simeone, R. et al. Cytosolic access of mycobacterium tuberculosis: critical impact of phagosomal acidification control and demonstration of occurrence in vivo. PLoS Pathog. 11, e1004650 (2015).
Bussi, C. & Gutierrez, M. G. Mycobacterium tuberculosis infection of host cells in space and time. FEMS Microbiol. Rev. 43, 341–361 (2019).
pubmed: 30916769
pmcid: 6606852
doi: 10.1093/femsre/fuz006
Bold, T. D., Banaei, N., Wolf, A. J. & Ernst, J. D. Suboptimal activation of antigen-specific cD4+ effector cells enables persistence of M. tuberculosis in vivo. PLoS Pathog. 7, 1–13 (2011).
doi: 10.1371/journal.ppat.1002063
Scanga, C. A. et al. Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2. J. Exp. Med. 192, 347–358 (2000).
pubmed: 10934223
pmcid: 2193220
doi: 10.1084/jem.192.3.347
Gallegos, A. M. et al. A gamma interferon independent mechanism of CD4 T cell mediated control of M. tuberculosis infection in vivo. PLoS Pathog. 7, 1–8 (2011).
doi: 10.1371/journal.ppat.1002052
Su, X. et al. Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation. Nat. Immunol. 16, 838–849 (2015).
pubmed: 26147685
pmcid: 4509841
doi: 10.1038/ni.3205
Singh, K. H. et al. Characterization of a secretory hydrolase from Mycobacterium tuberculosis sheds critical insight into host lipid utilization by M. tuberculosis. J. Biol. Chem. 292, 11326–11335 (2017).
pubmed: 28515317
pmcid: 5500798
doi: 10.1074/jbc.M117.794297
Katona, A., Toşa, M. I., Paizs, C. & Rétey, J. Inhibition of histidine ammonia lyase by heteroaryl-alanines and acrylates. Chem. Biodivers. 3, 502–508 (2006).
pubmed: 17193285
doi: 10.1002/cbdv.200690053
Lane, R. S., Manning, J. M. & Snell, E. E. Histidine decarboxylase of lactobacillus 30a: inactivation and active-site labeling by l-histidine methyl ester. Biochemistry 15, 4180–4185 (1976).
pubmed: 963031
doi: 10.1021/bi00664a008
Brand, L. M. & Harper, A. E. Histidine ammonia-lyase from rat liver. purification, properties, and inhibition by substrate analogs. Biochemistry 15, 1814–1821 (1976).
pubmed: 5116
doi: 10.1021/bi00654a005
Cross, A. J., Major, J. M., Rothman, N. & Sinha, R. Urinary 1-methylhistidine and 3-methylhistidine, meat intake, and colorectal adenoma risk. Eur. J. Cancer Prev. 23, 385–390 (2014).
pubmed: 24681531
pmcid: 4121566
doi: 10.1097/CEJ.0000000000000027
Schwartz, J. C., Rose, C. & Caillens, H. Metabolism of methylhistamine formed through a new pathway: decarboxylation of L-3-methylhistidine. J. Pharmacol. Exp. Ther. 184, 766–779 (1973).
pubmed: 4687236
Koul, A., Arnoult, E., Lounis, N., Guillemont, J. & Andries, K. The challenge of new drug discovery for tuberculosis. Nature 469, 483–490 (2011).
pubmed: 21270886
doi: 10.1038/nature09657
Cusumano, Z. T., Watson, M. E. & Caparon, M. G. Streptococcus pyogenes arginine and citrulline catabolism promotes infection and modulates innate immunity. Infect. Immun. 82, 233–242 (2014).
pubmed: 24144727
pmcid: 3911826
doi: 10.1128/IAI.00916-13
Gouzy, A. et al. Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection. PLoS Pathog. 10, e1003928 (2014).
Song, H. et al. Expression of the ompATb operon accelerates ammonia secretion and adaptation of Mycobacterium tuberculosis to acidic environments. Mol. Microbiol. 80, 900–918 (2011).
pubmed: 21410778
pmcid: 3091969
doi: 10.1111/j.1365-2958.2011.07619.x
Nguyen, N. T. et al. Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc. Natl Acad. Sci. USA 107, 19961–19966 (2010).
pubmed: 21041655
doi: 10.1073/pnas.1014465107
pmcid: 2993339
Boasso, A. et al. HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells. Blood 109, 3351–3359 (2007).
pubmed: 17158233
pmcid: 1852248
doi: 10.1182/blood-2006-07-034785
Gaardbo, J. C. et al. Increased tryptophan catabolism is associated with increased frequency of CD161+Tc17/MAIT cells and lower CD4+ T-Cell count in HIV-1 infected patients on cART after 2 years of follow-up. J. Acquir. Immune Defic. Syndr. 70, 228–235 (2015).
pubmed: 26470032
doi: 10.1097/QAI.0000000000000758
Ross, J. A., Howie, S. E. M., Norval, M., Maingay, J. & Simpson, T. J. Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice. J. Invest. Dermatol. 87, 630–633 (1986).
pubmed: 3021864
doi: 10.1111/1523-1747.ep12456257
Noonan, F. P. & De Fabo, E. C. Immunosuppression by ultraviolet B radiation: initiation by urocanic acid. Immunol. Today 13, 250–254 (1992).
pubmed: 1388651
doi: 10.1016/0167-5699(92)90005-R
Garssen, J., Norval, M., Crosby, J., Dortant, P. & Van Loveren, H. The role of urocanic acid in UVB-induced suppression of immunity to Trichinella spiralis infection in the rat. Immunology 96, 298–306 (1999).
pubmed: 10233709
pmcid: 2326747
doi: 10.1046/j.1365-2567.1999.00698.x
Bender, R. A. Regulation of the histidine utilization (Hut) system in bacteria. Microbiol. Mol. Biol. Rev. 76, 565–584 (2012).
pubmed: 22933560
pmcid: 3429618
doi: 10.1128/MMBR.00014-12
Vindal, V., Suma, K. & Ranjan, A. GntR family of regulators in Mycobacterium smegmatis: a sequence and structure based characterization. BMC Genomics 8, 289 (2007).
Kapopoulou, A., Lew, J. M. & Cole, S. T. The MycoBrowser portal: A comprehensive and manually annotated resource for mycobacterial genomes. Tuberculosis 91, 8–13 (2011).
pubmed: 20980200
doi: 10.1016/j.tube.2010.09.006
Dell, R. B., Holleran, S. & Ramakrishnan, R. Sample size determination. ILAR J. 43, 207–212 (2002).
pubmed: 12391396
doi: 10.1093/ilar.43.4.207
Bold, T. D. et al. Impaired fitness of Mycobacterium africanum despite secretion of ESAT-6. J. Infect. Dis. 205, 984–990 (2012).
pubmed: 22301632
pmcid: 3282571
doi: 10.1093/infdis/jir883
Ates, L. S. et al. The ESX-5 system of pathogenic mycobacteria is involved in capsule integrity and virulence through its substrate PPE10. PLoS Pathog. 12, e1005696 (2016).
Athar, A. et al. ArrayExpress update - From bulk to single-cell expression data. Nucleic Acids Res. 47, D711–D715 (2019).
pubmed: 30357387
doi: 10.1093/nar/gky964