title: Trafficking of superinfecting Mycobacterium organisms into established granulomas occurs in mammals and is independent of the Erp and ESX-1 mycobacterial virulence loci.
abstract: Although tuberculous granulomas, which are composed of infected macrophages and other immune cells, have long been considered impermeable structures, recent studies have shown that superinfecting Mycobacterium marinum traffic rapidly to established fish and frog granulomas by host-mediated and Mycobacterium-directed mechanisms. The present study shows that superinfecting Mycobacterium tuberculosis and Mycobacterium bovis bacille Calmette-Guérin similarly home to established granulomas in mice. Furthermore, 2 prominent mycobacterial virulence determinants, Erp and ESX-1, do not affect this cellular trafficking. These findings suggest that homing of infected macrophages to sites of infection is a general feature of the pathogenesis of tuberculosis and has important consequences for therapeutic strategies.
authors.affiliation: Departments of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Cosma
authors.forename: Olivier
authors.initials: O
authors.lastname: Humbert
authors.forename: David R
authors.initials: DR
authors.lastname: Sherman
authors.forename: Lalita
authors.initials: L
authors.lastname: Ramakrishnan
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002633:Chemotaxis; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006099:Granuloma / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000382:microbiology*; D009163:Mycobacterium bovis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D015163:Superinfection; D014774:Virulence
chemical_list: D001426:Bacterial Proteins