Open AccessDeletion of the Mycobacterium tuberculosis α-Crystallin-Like hspX Gene Causes Increased Bacterial Growth In Vivo
Author(s) -
Yan Hu,
Farahnaz Movahedzadeh,
Neil G. Stoker,
Anthony R. M. Coates
Publication year - 2006
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.74.2.861-868.2006
Subject(s) - mutant , biology , mycobacterium tuberculosis , in vivo , virulence , microbiology and biotechnology , gene , gene expression , in vitro , transcription (linguistics) , wild type , tuberculosis , genetics , medicine , linguistics , philosophy , pathology
Hypervirulent mutants ofMycobacterium tuberculosis , whose growth rates are higher in vivo, have now been reported to have mutations in both regulatory and structural genes, but the basis for this unusual phenotype is not understood. One hypervirulence gene,dosR (devR , Rv2031c), activates transcription of approximately 50 genes in this pathogen in response to hypoxia and nitric oxide stress. The most dramatic activation (∼80-fold) is activation of thehspX (acr , Rv2031c) gene, which encodes a 16-kDa α-crystallin-like protein that is a major antigen. In this study we found that a Δacr mutant exhibited increased growth following infection of BALB/c mice in vivo and in both resting and activated macrophages in vitro (as measured by the number of CFU). The increased growth in macrophages was equal to that of a ΔdosR mutant, while introduction of a constitutively expressedhspX gene reduced the ΔdosR virulence to wild-type levels. These results suggest that the increased number of CFU of the ΔdosR mutant was largely due to loss ofhspX expression. We also confirmed that constitutive expression ofhspX slows growth in vitro, and we propose thathspX plays an active role in slowing the growth ofM. tuberculosis in vivo immediately following infection.