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An increase in expression of a Mycobacterium tuberculosis mycolyl transferase gene ( fbpB ) occurs early after infection of human monocytes
Author(s) -
Wilkinson Robert J.,
DesJardin Lucy E.,
Islam Najmul,
Gibson Brandon M.,
Kanost R. Andrew,
Wilkinson Katalin A.,
Poelman David,
Eisenach Kathleen D.,
Toossi Zahra
Publication year - 2001
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2001.02280.x
Subject(s) - biology , mycobacterium tuberculosis , immune system , antigen , tumor necrosis factor alpha , secretion , microbiology and biotechnology , tuberculosis , messenger rna , monocyte , gene , immunology , biochemistry , medicine , pathology
Changes in the mRNA levels of two Mycobacterium tuberculosis genes ( fbp B known as antigen 85B, and hsp X known as Acr) were studied in infected human monocytes. Antigen 85B is an enzyme involved in cell wall biosynthesis and is also a major target of the immune response. Acr is a stress protein believed to be involved in the bacillary response to adverse conditions and in non‐replicating persistence. During the first 24 h of intracellular infection, the intramonocyte 85B mRNA level increased 54‐fold ( P = 0.00001) and 14.6 times in comparison with the 16S ribosomal rRNA. In contrast, the Acr mRNA fell 14.3 times. Although monocyte cytokine production was very variable, the 24 h secretion of tumour necrosis factor (TNF)‐α correlated with the 85B−16S RNA ratio at 24 h ( r = 0.77, P corr < 0.01). Furthermore, the addition of exogenous TNF‐α to cultures was associated with a twofold increase in the 85B−16S ratio and, conversely, neutralization of endogenous TNF‐α reduced the ratio. As antigen 85B also induces TNF‐α, the positive feedback implied by our findings suggests a previously unsuspected role for this protein in the immunopathogenesis of tuberculosis.