{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:58:37Z","timestamp":1790787517473,"version":"4.1.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    causes tuberculosis, an infectious disease; this acid-fast bacillus has various functions that enable it to survive within the host. Importantly, the type VII secretion system plays a vital role in host immune evasion. However, the early secretory antigenic target secretion system (ESX) component is crucial for mycobacteria survival, plays a significant role in bypassing the host immune response, and is linked to the prognosis of the disease. The review aims to analyze the ESX-associated genes\u2019 functions in defence mechanisms against host immune response. There are five types of ESX, with the ESX-1 effectors consisting of the heterodimers\n                    <jats:italic>EsxA\/<\/jats:italic>\n                    ESAT-6 and\n                    <jats:italic>EsxB<\/jats:italic>\n                    \/CFP-10. The precise membranolytic role of\n                    <jats:italic>EsxA<\/jats:italic>\n                    remains unclear; however, mycobacterial mutants deficient in\n                    <jats:italic>EsxA<\/jats:italic>\n                    show reduced membrane lytic activity and lack the ability to perforate phagosomes. ESX-5 substrates, such as glycine-rich and repetitive\n                    <jats:italic>PE_PGRS<\/jats:italic>\n                    proteins, are associated with immune evasion and pathogenicity. ESX-5 releases a substantial amount of PE and PPE proteins, along with various other immune-modulating substrates. In addition, ESX-3 facilitates iron acquisition through mycobactin and regulates metal homeostasis. ESX 4 has been studied in two fast-growing mycobacterial species:\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    and\n                    <jats:italic>M. smegmatis<\/jats:italic>\n                    . Notably, conjugal DNA transfer in the recipient strain of\n                    <jats:italic>M. smegmatis<\/jats:italic>\n                    requires ESX-4. Therefore, the type VII secretion system of ESX-associated genes plays a crucial role in bacterial survival and action against autophagosome-lysosome fusion. Thus, studying this system will explore the effects of specific antigenic structures and their relationships with autophagy and mycobacterial self-defense mechanisms.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1797994","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:29:56Z","timestamp":1775539796000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional analysis of type VII secretion system links to host immune evasion mechanism in Mycobacterium tuberculosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Karthikeyan","family":"Sundaram","sequence":"first","affiliation":[{"name":"Department of Herbal Pharmacology and Environmental Sustainability, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education","place":["Kelambakkam, Kanchipuram, Tamilnadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Rathinam","sequence":"additional","affiliation":[{"name":"Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education","place":["Kelambakkam, Kanchipuram, Tamilnadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramalingam","family":"Bethunaickan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Indian Council of Medical Research (ICMR)- National institute for Research in Tuberculosis","place":["Chennai, Tamilnadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma Devi","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Indian Council of Medical Research (ICMR)- National institute for Research in Tuberculosis","place":["Chennai, Tamilnadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkataraman","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Division of Medical Research, SRM Medical College Hospital and Research Centre, Kattankulathur","place":["Chennai, Tamilnadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhavan","family":"Dhanapal","sequence":"additional","affiliation":[{"name":"Department of Immunology, Indian Council of Medical Research (ICMR)- National institute for Research in Tuberculosis","place":["Chennai, Tamilnadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3243","DOI":"10.1007\/s12033-024-01260-0","article-title":"A simple and rapid method of probiotic bacterial ghost cell preparation to deliver Mycobacterium tuberculosis antigen","volume":"67","author":"Aarthi","year":"2025","journal-title":"Mol. Biotechnol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"7166","DOI":"10.4049\/jimmunol.181.10.7166","article-title":"The ESX-5 secretion system of Mycobacterium marinum modulates the macrophage response","volume":"181","author":"Abdallah","year":"2008","journal-title":"J. Immunol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0211003","article-title":"Integrated transcriptomic and proteomic analysis of pathogenic mycobacteria and their esx-1 mutants reveal secretion-dependent regulation of ESX-1 substrates and WhiB6 as a transcriptional regulator","volume":"14","author":"Abdallah","year":"2019","journal-title":"PLoS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"S168","DOI":"10.1016\/j.ijtb.2025.06.004","article-title":"The spectrum of extra pulmonary tuberculosis: Emphasizing the importance of microbiological diagnosis- A case series","volume":"72","author":"Aghoram","year":"2025","journal-title":"Indian J. Tuberc"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5785","DOI":"10.1074\/jbc.RA119.012497","article-title":"N\u03b1-acetylation of the virulence factor EsxA is required for mycobacterial cytosolic translocation and virulence","volume":"295","author":"Aguilera","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s00284-023-03360-7","article-title":"Rv3539 (PPE63) of Mycobacterium tuberculosis promotes survival of Mycobacterium smegmatis in human macrophages cell line via cell wall modulation of bacteria and altering host\u2019s immune response","volume":"80","author":"Anand","year":"2023","journal-title":"Curr. Microbiol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005190","article-title":"Essential role of the ESX-5 secretion system in outer membrane permeability of pathogenic mycobacteria","volume":"11","author":"Ates","year":"2015","journal-title":"PloS Genet."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12726","article-title":"ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis","volume":"19","author":"Augenstreich","year":"2017","journal-title":"Cell. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.91930","article-title":"ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6-specific nanobody restricts M. tuberculosis growth in macrophages","volume":"12","author":"Bates","year":"2024","journal-title":"Elife"},{"key":"B10","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.jinf.2019.06.001","article-title":"ESAT-6 modulates Calcimycin-induced autophagy through microRNA-30a in mycobacteria infected macrophages","volume":"79","author":"Behura","year":"2019","journal-title":"J. Infect."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.862582","article-title":"Mycobacterium tuberculosis induces Irg1 in murine macrophages by a pathway involving both TLR-2 and STING\/IFNAR signaling and requiring bacterial phagocytosis","volume":"12","author":"Bomfim","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"E10772","DOI":"10.1073\/pnas.1710167114","article-title":"WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum","volume":"114","author":"Bosserman","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00760-18","article-title":"A new ESX-1 substrate in Mycobacterium marinum that is required for hemolysis but not host cell lysis","volume":"201","author":"Bosserman","year":"2019","journal-title":"J. Bacteriol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1128\/IAI.74.1.88-98.2006","article-title":"Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence","volume":"74","author":"Brodin","year":"2006","journal-title":"Infect. Immun."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00402-23","article-title":"Reconstitution of a minimal ESX-5 type VII secretion system suggests a role for PPE proteins in the outer membrane transport of proteins","volume":"8","author":"Bunduc","year":"2023","journal-title":"mSphere"},{"key":"B16","doi-asserted-by":"publisher","first-page":"16880","DOI":"10.1074\/jbc.M117.802645","article-title":"Structural basis of the PE-PPE protein interaction in Mycobacterium tuberculosis","volume":"292","author":"Chen","year":"2017","journal-title":"J. Biol. Chem."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00289-20","article-title":"Conserved ESX-1 substrates EspE and EspF are virulence factors that regulate gene expression","volume":"88","author":"Chirakos","year":"2020","journal-title":"Infect. Immun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.chom.2018.08.001","article-title":"Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination","volume":"24","author":"Cohen","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00987-23","article-title":"An N-acetyltransferase required for ESAT-6 N-terminal acetylation and virulence in Mycobacterium marinum","volume":"14","author":"Collars","year":"2023","journal-title":"mBio"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.04685-22","article-title":"Transcriptomic profile of the most successful Mycobacterium tuberculosis strain in Aragon, the MtZ strain, during exponential and stationary growth phases","volume":"11","author":"Com\u00edn","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1073\/pnas.1620133114","article-title":"Mycobacterial ESX-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions","volume":"114","author":"Conrad","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B22","doi-asserted-by":"publisher","first-page":"5960","DOI":"10.1074\/jbc.RA119.011682","article-title":"Modification of a PE\/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system","volume":"295","author":"Damen","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.bbrc.2016.06.042","article-title":"ESAT6 inhibits autophagy flux and promotes BCG proliferation through MTOR","volume":"477","author":"Dong","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1021\/acsinfecdis.0c00741","article-title":"Protein synthesis and degradation inhibitors potently block Mycobacterium tuberculosis type-7 secretion system ESX-1 activity","volume":"7","author":"Drever","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1093\/gbe\/evw001","article-title":"Mycobacterial pan-genome analysis suggests important role of plasmids in the radiation of type VII secretion systems","volume":"8","author":"Dumas","year":"2016","journal-title":"Genome Biol. Evol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83094","article-title":"Roles for mycobacterial DinB2 in frameshift and substitution mutagenesis","volume":"12","author":"Dupuy","year":"2023","journal-title":"Elife"},{"key":"B27","doi-asserted-by":"publisher","first-page":"14758","DOI":"10.1073\/pnas.1409345111","article-title":"Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion","volume":"111","author":"Ekiert","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00660-18","article-title":"Mycobacterium tuberculosis requires regulation of ESX-5 secretion for virulence in Irgm1-deficient mice","volume":"87","author":"Elliott","year":"2019","journal-title":"Infect. Immun."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/srep17078","article-title":"Impact of Mycobacterium tuberculosis RD1-locus on human primary dendritic cell immune functions","volume":"5","author":"Etna","year":"2015","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1186\/s13104-017-2752-0","article-title":"Two promoters in the esx-3 gene cluster of Mycobacterium smegmatis respond inversely to different iron concentrations in vitro","volume":"10","author":"Fang","year":"2017","journal-title":"BMC Res. Notes"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10112749","article-title":"Recent developments in mycobacteria-based live attenuated vaccine candidates for tuberculosis","volume":"10","author":"Flores-Valdez","year":"2022","journal-title":"Biomedicines"},{"key":"B32","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.crstbi.2021.06.001","article-title":"Priming mycobacterial ESX-secreted protein B to form a channel-like structure","volume":"3","author":"Gijsbers","year":"2021","journal-title":"Curr. Res. Struct. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.chembiol.2023.12.007","article-title":"Discovery of dual-active ethionamide boosters inhibiting the Mycobacterium tuberculosis ESX-1 secretion system","volume":"31","author":"Gries","year":"2024","journal-title":"Cell Chem. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1080\/22221751.2020.1861913","article-title":"Mycobacterium tuberculosis ESX-1-secreted substrate protein EspC promotes mycobacterial survival through endoplasmic reticulum stress-mediated apoptosis","volume":"10","author":"Guo","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"B35","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1007\/s00203-023-03576-y","article-title":"Mycobacterium tuberculosis virulence factors EsxB and PPE68 on host cells","volume":"205","author":"Guo","year":"2021","journal-title":"Archives of microbiology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1084\/jem.20172020","article-title":"Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny","volume":"215","author":"Huang","year":"2018","journal-title":"J. Exp. Med."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02983-20","article-title":"Mycobacterium tuberculosis toxin CpnT is an ESX-5 substrate and requires three type VII secretion systems for intracellular secretion","volume":"12","author":"Izquierdo Lafuente","year":"2021","journal-title":"mBio"},{"key":"B38","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1111\/mmi.12770","article-title":"Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG5 in complex with PE25-PPE41 dimer","volume":"94","author":"Korotkova","year":"2014","journal-title":"Mol. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.chom.2015.01.007","article-title":"MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-\u03baB pathway","volume":"17","author":"Kumar","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1172\/JCI84978","article-title":"ESAT-6-dependent cytosolic pattern recognition drives noncognate tuberculosis control in vivo","volume":"126","author":"Kupz","year":"2016","journal-title":"J. Clin. Invest."},{"key":"B41","doi-asserted-by":"publisher","first-page":"17083","DOI":"10.1074\/jbc.RA120.013017","article-title":"A novel stress-inducible CmtR-ESX3-Zn2+ regulatory pathway essential for survival of Mycobacterium bovis under oxidative stress","volume":"295","author":"Li","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02764-22","article-title":"Intragranuloma accumulation and inflammatory differentiation of neutrophils underlie mycobacterial ESX-1-dependent immunopathology","volume":"14","author":"Lienard","year":"2023","journal-title":"mBio"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1073\/pnas.1911646117","article-title":"The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms","volume":"117","author":"Lienard","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00060-22","article-title":"Mycobacterium tuberculosis EspK has active but distinct roles in the secretion of EsxA and EspB","volume":"204","author":"Lim","year":"2022","journal-title":"J. Bacteriol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s11010-019-03522-x","article-title":"Early secreted antigenic target of 6-kDa of Mycobacterium tuberculosis promotes caspase-9\/caspase-3-mediated apoptosis in macrophages","volume":"457","author":"Lin","year":"2019","journal-title":"Mol. Cell. Biochem."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00216","article-title":"Mutations in efflux pump Rv1258c (Tap) cause resistance to pyrazinamide, isoniazid, and streptomycin in M. tuberculosis","volume":"10","author":"Liu","year":"2019","journal-title":"Front. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/mmi.13575","article-title":"EspC forms a filamentous structure in the cell envelope of Mycobacterium tuberculosis and impacts ESX-1 secretion","volume":"103","author":"Lou","year":"2017","journal-title":"Mol. Microbiol."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03762-24","article-title":"Frequently arising ESX-1-associated phase variants influence Mycobacterium tuberculosis fitness in the presence of host and antibiotic pressures","volume":"16","author":"Luna","year":"2025","journal-title":"mBio"},{"key":"B49","doi-asserted-by":"publisher","first-page":"48a","DOI":"10.1186\/1471-2180-9-48","article-title":"Transcriptional analysis of ESAT-6 cluster 3 in Mycobacterium smegmatis","volume":"9","author":"Maciag","year":"2009","journal-title":"BMC Microbiol."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00965-21","article-title":"ESX-1-independent horizontal gene transfer by Mycobacterium tuberculosis complex strains","volume":"12","author":"Madacki","year":"2021","journal-title":"mBio"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.4049\/jimmunol.2300001","article-title":"High bacillary burden and the ESX-1 type VII secretion system promote MHC class I presentation by Mycobacterium tuberculosis-infected macrophages to CD8 T cells","volume":"210","author":"Mott","year":"2023","journal-title":"J. Immunol."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1186\/s12862-016-0631-2","article-title":"The plasmid-mediated evolution of the mycobacterial ESX (Type VII) secretion systems","volume":"16","author":"Newton-Foot","year":"2016","journal-title":"BMC Evol. Biol."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03357-23","article-title":"The antagonistic transcription factors, EspM and EspN, regulate the ESX-1 secretion system in M. marinum","volume":"15","author":"Nicholson","year":"2024","journal-title":"mBio"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000505","article-title":"Pathogenomic analyses of Mycobacterium microti, an ESX-1-deleted member of the Mycobacterium tuberculosis complex causing disease in various hosts","volume":"7","author":"Orgeur","year":"2021","journal-title":"Microb. Genom."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2122161119","article-title":"The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence","volume":"119","author":"Osman","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens13121041","article-title":"Functional analysis of promoters, mRNA cleavage, and mRNA secondary structure on esxB-esxA in Mycolicibacterium smegmatis","volume":"13","author":"Peters","year":"2024","journal-title":"Pathogens"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjsbx.2020.100029","article-title":"High resolution CryoEM structure of the ring-shaped virulence factor EspB from Mycobacterium tuberculosis","volume":"4","author":"Piton","year":"2020","journal-title":"J. Struct. Biol. X"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52983","article-title":"The structure of the endogenous ESX-3 secretion system","volume":"8","author":"Poweleit","year":"2019","journal-title":"Elife"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00271-24","article-title":"The regulatory functions of ESX-1 substrates, EspE and EspF, are separable from secretion","volume":"206","author":"Prest","year":"2024","journal-title":"J. Bacteriol."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00148-17","article-title":"The cell wall lipid PDIM contributes to phagosomal escape and host cell exit of Mycobacterium tuberculosis","volume":"8","author":"Quigley","year":"2017","journal-title":"mBio"},{"key":"B61","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1128\/IAI.70.7.3371-3381.2002","article-title":"ideR, an essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response","volume":"70","author":"Rodriguez","year":"2002","journal-title":"Infect. Immun."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.4161\/auto.20881","article-title":"ESX-1 dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendritic cells","volume":"8","author":"Romagnoli","year":"2012","journal-title":"Autophagy"},{"key":"B63","doi-asserted-by":"publisher","first-page":"19665","DOI":"10.1073\/pnas.1907631116","article-title":"Phase variation in Mycobacterium tuberculosis glpK produces transiently heritable drug tolerance","volume":"116","author":"Safi","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02807-19","article-title":"EspM is a conserved transcription factor that regulates gene expression in response to the ESX-1 system","volume":"11","author":"Sanchez","year":"2020","journal-title":"mBio"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00573-22","article-title":"Role of the Mycobacterium tuberculosis ESX-4 secretion system in heme iron utilization and pore formation by PPE proteins","volume":"8","author":"Sankey","year":"2023","journal-title":"mSphere"},{"key":"B66","doi-asserted-by":"publisher","first-page":"20848","DOI":"10.1073\/pnas.2003235117","article-title":"Mucosal delivery of ESX-1-expressing BCG strains provides superior immunity against tuberculosis in murine type 2 diabetes","volume":"117","author":"Sathkumara","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104589","article-title":"Cryo-EM reveals the membrane-binding phenomenon of EspB, a virulence factor of the mycobacterial type VII secretion system","volume":"299","author":"Sengupta","year":"2023","journal-title":"J. Biol. Chem."},{"key":"B68","doi-asserted-by":"publisher","first-page":"6340","DOI":"10.1128\/JB.00756-09","article-title":"Characterization of a Mycobacterium tuberculosis ESX-3 conditional mutant: essentiality and rescue by iron and zinc","volume":"191","author":"Serafini","year":"2009","journal-title":"J. Bacteriol."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078351","article-title":"The ESX-3 secretion system is necessary for iron and zinc homeostasis in Mycobacterium tuberculosis","volume":"8","author":"Serafini","year":"2013","journal-title":"PloS One"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001230","article-title":"Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling","volume":"6","author":"Shin","year":"2010","journal-title":"PloS Pathog."},{"key":"B71","doi-asserted-by":"publisher","first-page":"S150","DOI":"10.1016\/j.tube.2015.02.019","article-title":"ESX\/type VII secretion systems of mycobacteria: Insights into evolution, pathogenicity and protection","volume":"95","author":"Simeone","year":"2015","journal-title":"Tuberculosis (Edinb)"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74419","article-title":"Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice","volume":"11","author":"Smith","year":"2022","journal-title":"Elife"},{"key":"B73","doi-asserted-by":"publisher","first-page":"e00662","DOI":"10.1128\/JB.00662-19","article-title":"Polarly localized EccE1 is required for ESX-1 function and stabilization of ESX-1 membrane proteins in Mycobacterium tuberculosis","volume":"202","author":"Soler-Arnedo","year":"2020","journal-title":"J. Bacteriol."},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2023.105239","article-title":"Efflux pump Rv1258c activates novel functions of the oxidative stress and via the VII secretion system ESX-3-mediated iron metabolic pathway in Mycobacterium tuberculosis","volume":"26","author":"Sun","year":"2024","journal-title":"Microbes Infect."},{"key":"B75","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41420-021-00716-5","article-title":"Gasdermin D mediates host cell death but not interleukin-1\u03b2 secretion in Mycobacterium tuberculosis-infected macrophages","volume":"7","author":"Theobald","year":"2021","journal-title":"Cell. Death Discov."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2023113490","article-title":"Uptake-independent killing of macrophages by extracellular Mycobacterium tuberculosis aggregates","volume":"42","author":"Toniolo","year":"2023","journal-title":"EMBO J."},{"key":"B77","doi-asserted-by":"publisher","first-page":"E348","DOI":"10.1073\/pnas.1523321113","article-title":"Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence","volume":"113","author":"Tufariello","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B78","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jmb.2018.11.003","article-title":"Structural variability of EspG chaperones from mycobacterial ESX-1, ESX-3, and ESX-5 type VII secretion systems","volume":"431","author":"Tuukkanen","year":"2019","journal-title":"J. Mol. Biol."},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2301394120","article-title":"Phase variation as a major mechanism of adaptation in Mycobacterium tuberculosis complex","volume":"120","author":"Vargas","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B80","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1007\/s13238-019-00671-z","article-title":"Structural insights into substrate recognition by the type VII secretion system","volume":"11","author":"Wang","year":"2020","journal-title":"Protein Cell"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103585","article-title":"Crosstalk between the ancestral type VII secretion system ESX-4 and other T7SS in Mycobacterium marinum","volume":"25","author":"Wang","year":"2021","journal-title":"iScience"},{"key":"B82","doi-asserted-by":"publisher","first-page":"12706","DOI":"10.1074\/jbc.RA120.012698","article-title":"PE5-PPE4-EspG3 heterotrimer structure from mycobacterial ESX-3 secretion system gives insight into cognate substrate recognition by ESX systems","volume":"295","author":"Williamson","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B83","volume-title":"Global tuberculosis report 2024","year":"2024"},{"key":"B84","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.intimp.2019.04.056","article-title":"Mycobacterium marinum down-regulates miR-148a in macrophages in an EsxA-dependent manner","volume":"73","author":"Wu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00217-24","article-title":"The SapM phosphatase can arrest phagosome maturation in an ESX-1 independent manner in Mycobacterium tuberculosis and BCG","volume":"92","author":"Xander","year":"2024","journal-title":"Infect. Immun."},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2020.183515","article-title":"Secondary structure and transmembrane topology analysis of the N-terminal domain of the inner membrane protein EccE1 from M. smegmatis using site-directed spin labeling EPR","volume":"1863","author":"Yu","year":"2021","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"B87","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12931-025-03210-z","article-title":"Early secretory antigen target of 6-kDa of Mycobacterium tuberculosis inhibits macrophage apoptosis and host defense via TLR2","volume":"26","author":"Zhang","year":"2025","journal-title":"Respir. Res."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adq8158","article-title":"Single-cell analysis reveals Mycobacterium tuberculosis ESX-1-mediated accumulation of permissive macrophages in infected mouse lungs","volume":"11","author":"Zheng","year":"2025","journal-title":"Sci. Adv."},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00088-20","article-title":"The ESX-1 virulence factors downregulate miR-147-3p in Mycobacterium marinum-infected macrophages","volume":"88","author":"Zuo","year":"2020","journal-title":"Infect. Immun."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1797994\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:29:59Z","timestamp":1775539799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1797994\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":89,"alternative-id":["10.3389\/fcimb.2026.1797994"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1797994","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"article-number":"1797994"}}