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Mycobacterium tuberculosis modulates its cell surface via an oligopeptide permease (Opp) transport system.

ABSTRACT: Bacterial species utilize a vast repertoire of surface structures to interact with their surroundings and employ a number of strategies to reconfigure the cellular envelope according to specific stimuli. Gram-positive bacteria, exemplified by Streptomyces and Bacillus species, control production of some exposed molecules by importing oligopeptide signals via permeases (Opp). Such oligopeptides modulate intracellular signaling pathways. In this work, we functionally characterized an Opp of the human pathogen Mycobacterium tuberculosis (Mtb) and propose its reannotation. Using genome-wide transcriptional profiling, we found that Opp was required to modulate (fold-change ranging from -3.5 to 2.0) the expression of several genes, most of them encoding surface-exposed molecules. These included the virulence-associated lipids mycolic acids and phthiocerol dimycocerosates (PDIMs) as well as PE-family proteins. By thin-layer chromatography and MALDI-TOF-MS we confirmed changes in the lipid profile, including an altered accumulation of triacylglycerides and an affected ratio of mycolic acids to PDIMs. An Opp loss of function mutant showed no in vitro growth defect, but had diminished burden during chronic infection and produced a slightly delayed time to death of animals when compared to WT Mtb infection.

SUBMITTER: Flores-Valdez MA

PROVIDER: S-EPMC2812042 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Mycobacterium tuberculosis modulates its cell surface via an oligopeptide permease (Opp) transport system.

Flores-Valdez Mario Alberto MA Morris Rowan P RP Laval Françoise F Daffé Mamadou M Schoolnik Gary K GK

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20090811 12

Bacterial species utilize a vast repertoire of surface structures to interact with their surroundings and employ a number of strategies to reconfigure the cellular envelope according to specific stimuli. Gram-positive bacteria, exemplified by Streptomyces and Bacillus species, control production of some exposed molecules by importing oligopeptide signals via permeases (Opp). Such oligopeptides modulate intracellular signaling pathways. In this work, we functionally characterized an Opp of the hu ...[more]

PMID: 19671666

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Project description:The DosR regulon in Mycobacterium tuberculosis is involved in respiration-limiting conditions and its induction is controlled by two histidine kinases, DosS and DosT. Recent experimental evidence indicates DosS senses either molecular oxygen or a redox change. This report demonstrates that DosS responds to a reduced electron transport system (ETS), although this does not rule out a role for oxygen in silencing signaling. Under aerobic conditions induction of the DosR regulon by DosS but not DosT was observed after the addition of ascorbate, a powerful cytochrome c reductant, demonstrating DosS responds to a redox signal even in the presence of high oxygen tension. During hypoxic conditions regulon induction was attenuated by treatment with compounds that occluded electron flow into the menaquinone pool or decreased the size of the menaquinone pool itself. Increased regulon expression during hypoxia was observed when exogenous menaquinone was added, demonstrating the menaquinone pool is a limiting factor in regulon induction. Taken together these data indicate that a reduced menaquinone pool directly or indirectly triggers induction of the DosR regulon via DosS. Biochemical analysis of menaquinones upon entry into hypoxic/anaerobic conditions demonstrated the disappearance of the unsaturated species and low-level maintenance of the mono-saturated menaquinone. Relative to the unsaturated form, an analog of the saturated form is better able to induce signaling via DosS, rescue inhibition of menaquinone synthesis, and is less toxic. The menaquinone pool is central to the ETS and therefore provides a mechanistic link between the respiratory state of the bacilli and DosS signaling. Aerobically growing logarithmic phase DosS and DosT mutant strains were analyzed after treatment with the cytochrome c reductant ascorbate to examine the effect on DosR signaling caused by reducing the electron transport system. Experiments were repeated in triplicate (dosT mutant) or duplicate (dosS mutant).

Dataset Information

Mycobacterium tuberculosis modulates its cell surface via an oligopeptide permease (Opp) transport system.

Publications

Mycobacterium tuberculosis modulates its cell surface via an oligopeptide permease (Opp) transport system.

Similar Datasets

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