{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T18:50:56Z","timestamp":1775155856674,"version":"3.50.1"},"reference-count":29,"publisher":"Microbiology Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,6,1]]},"abstract":"<jats:p>Secondary sigma factors in bacteria direct transcription of defence regulons in response to specific stresses. To identify which sigma factors in the human respiratory pathogen <jats:italic>Mycobacterium tuberculosis<\/jats:italic> are important for adaptive survival <jats:italic>in vivo<\/jats:italic>, defined null mutations were created in individual sigma factor genes. In this study, <jats:italic>in vitro<\/jats:italic> growth virulence and guinea pig pathology of <jats:italic>M. tuberculosis<\/jats:italic> mutants lacking functional sigma factors (SigC, SigF, or SigM) were compared to the parent strain, H37Rv. None of the mutant strains exhibited a growth deficiency in Middlebrook 7H9 broth, nor were any impaired for intracellular replication in the human monocytic macrophage cell-line THP-1. Following low-dose aerosol infection of guinea pigs, however, differences could be detected. While a SigM mutant resulted in lung and spleen granulomas of comparable composition to those found in H37Rv-infected animals, a SigF mutant was partially attenuated, exhibiting necrotic spleen granulomas and ill-defined lung granulomas. SigC mutants exhibited attenuation in the lung and spleen; notably, necrotic granulomas were absent. These data suggest that while SigF may be important for survival in the lung, SigC is likely a key regulator of pathogenesis and adaptive survival in the lung and spleen. Understanding how SigC mediates survival in the host should prove useful in the development of anti-tuberculosis therapies.<\/jats:p>","DOI":"10.1099\/mic.0.28591-0","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:40:51Z","timestamp":1149064851000},"page":"1591-1600","source":"Crossref","is-referenced-by-count":50,"title":["Examination of Mycobacterium tuberculosis sigma factor mutants using low-dose aerosol infection of guinea pigs suggests a role for SigC in pathogenesis"],"prefix":"10.1099","volume":"152","author":[{"given":"Russell K.","family":"Karls","sequence":"first","affiliation":[{"name":"Mycobacteriology Laboratory Branch, Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA"},{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeannette","family":"Guarner","sequence":"additional","affiliation":[{"name":"Infectious Disease Pathology Activity, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David N.","family":"McMurray","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, College Station, TX 77845, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin A.","family":"Birkness","sequence":"additional","affiliation":[{"name":"Mycobacteriology Laboratory Branch, Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick D.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Mycobacteriology Laboratory Branch, Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA"},{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"7170","DOI":"10.1128\/IAI.71.12.7170-7172.2003","article-title":"Deletion of M. tuberculosis sigma factor E results in delayed time to death with bacterial persistence in the lungs of aerosol-infected mice","volume":"71","author":"Ando","year":"2003","journal-title":"Infect Immun"},{"key":"R2","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1128\/IAI.66.6.2951-2959.1998","article-title":"Evaluation of new vaccines in the mouse and guinea pig model of TB","volume":"66","author":"Baldwin","year":"1998","journal-title":"Infect Immun"},{"key":"R3","doi-asserted-by":"crossref","first-page":"5575","DOI":"10.1128\/IAI.68.10.5575-5580.2000","article-title":"Construction and characterization of a M. tuberculosis mutant lacking the alternate sigma factor gene, sigF","volume":"68","author":"Chen","year":"2000","journal-title":"Infect Immun"},{"key":"R4","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/31159","article-title":"Deciphering the biology of M. tuberculosis from the complete genome sequence","volume":"393","author":"Cole","year":"1998","journal-title":"Nature"},{"key":"R5","volume-title":"Robbins Pathologic Basis of Disease","author":"Cotran","year":"1999"},{"key":"R6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/jama.282.7.677","article-title":"Consensus statement. 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