Response of Mycobacterium tuberculosis to Reactive Oxygen and Nitrogen Intermediates

Abstract

Background: Mycobacterium tuberculosis is a significant human pathogen capable of replicating in mononuclear phagocytic cells. Exposure to reactive oxygen and nitrogen intermediates is likely to represent an important aspect of the life cycle of this organism. The response of M. tuberculosis to these agents may be of significance for its survival in the host.

A cooperative oxygen-binding hemoglobin from Mycobacterium tuberculosis

“…The bacillus, in turn, has evolved a defense mechanism against reactive nitrogen intermediates. Recently, the expression of a set of proteins in response to the presence of reactive nitrogen intermediates was indeed reported in M. tuberculosis (53,54), and a gene conferring resistance to these intermediates was cloned (55). That the oxygenated form of HbN is involved in the protection of the bacilli against reactive nitrogen species produced in the granuloma during latency is supported by the observation that the expression of HbN is elevated in the stationary phase during cell growth in vitro.…”

Expression of Th1-mediated immunity in mouse lungs induces aMycobacterium tuberculosistranscription pattern characteristic of nonreplicating persistence

“…Furthermore, acr, one of the M. tuberculosis genes that is up-regulated at onset of Th1-mediated immunity (Fig. 5A), is also induced by addition of NO donors to in vitro cultures of tubercle bacilli (14).…”

“…Five genes (acr, rv2626c, rv2623, sodC, and sodA) were selected because their expression is known to be modulated when tubercle bacilli transition from exponential growth to either stationary phase or hypoxia-induced nonreplicating persistence, or to both. acr was chosen because it encodes a 16-kDa chaperonin that is up-regulated in vitro by hypoxia (13,15,25,26), during stationary phase of growth of aerated M. tuberculosis cultures (27), by addition of NO donors (14), and on ingestion of M. tuberculosis by cultured macrophages (28). Likewise, rv2626c, a gene of unknown function, was chosen because, like acr, it is up-regulated in vitro during stationary phase of growth of aerated cultures (29) and under hypoxic conditions (15,29,30).…”

“…Thus, mice incapable of making IFN-␥ (7,8) or NOS2 (9,10) or of generating NO (9,11) cannot control growth of tubercle bacilli in the lung. On the pathogen's side, much is known about the modulation of transcription in response to environmental changes during M. tuberculosis growth in vitro (12,(13)(14)(15) or when tubercle bacilli are ingested by macrophages in culture (16)(17)(18). However, there is little, if any, knowledge concerning shifts in transcription patterns of tubercle bacilli responding to defense mechanisms in a host animal.…”

Comparison of the proteome of Mycobacterium tuberculosis strain H37Rv with clinical isolate CDC 1551

“…Since the virulence of M. tuberculosis of H37Rv in man is unknown, comparison of its proteome with that of a recent clinical isolate will also test its relevance for use in studies aimed at the combat of human disease. Several recent studies of the proteome of M. tuberculosis have been reported including the analysis of cell lysates, culture-filtrate proteins and the response of M. tuberculosis to different environmental conditions (Lee & Horwitz, 1995 ;Garbe et al, 1996Garbe et al, , 1999Sonnenberg & Belisle, 1997 ;Urquhart et al, 1997Urquhart et al, , 1998Weldingh et al, 1998 ;Wong et al, 1999). The most comprehensive study to date, in terms of protein spot identification, compared two strains of Mycobacterium bovis bacille Calmette-Gue!…”