The Mycobacterium tuberculosis cysD and cysNC genes form a stress-induced operon that encodes a tri-functional sulfate-activating complex

Pinto, Rachel; Tang, Quing Xui; Britton, Warwick J.; Leyh, Thomas S.; Triccas, James A.

doi:10.1099/mic.0.26894-0

Cited by 81 publications

(86 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further indication is provided by the reduced expression in EU58 of the PP_1110-PP_1113 operon as well as the cysD and cysNC genes. These two genes have been shown to be induced by sulfur depletion and also by oxidative stress in Mycobacterium tuberculosis (25). All of these data and the fact that a roxSR mutant loses its ability to sense the population density signal that modulates ddcA expression indicate that this two-component system is a key element in a complex regulatory network.…”

Section: Discussionmentioning

confidence: 84%

A Two-Component Regulatory System Integrates Redox State and Population Density Sensing in Pseudomonas putida

et al. 2008

View full text Add to dashboard Cite

A two-component system formed by a sensor histidine kinase and a response regulator has been identified as an element participating in cell density signal transduction in Pseudomonas putida KT2440. It is a homolog of the Pseudomonas aeruginosa RoxS/RoxR system, which in turn belongs to the RegA/RegB family, described in photosynthetic bacteria as a key regulatory element. In KT2440, the two components are encoded by PP_0887 (roxS) and PP_0888 (roxR), which are transcribed in a single unit. Characterization of this twocomponent system has revealed its implication in redox signaling and cytochrome oxidase activity, as well as in expression of the cell density-dependent gene ddcA, involved in bacterial colonization of plant surfaces. Whole-genome transcriptional analysis has been performed to define the P. putida RoxS/RoxR regulon. It includes genes involved in sugar and amino acid metabolism and the sulfur starvation response and elements of the respiratory chain (a cbb3 cytochrome oxidase, Fe-S clusters, and cytochrome c-related proteins) or genes participating in the maintenance of the redox balance. A putative RoxR recognition element containing a conserved hexamer (TGCCAG) has also been identified in promoters of genes regulated by this two-component system.

show abstract

Section: Discussionmentioning

confidence: 84%

A Two-Component Regulatory System Integrates Redox State and Population Density Sensing in Pseudomonas putida

et al. 2008

View full text Add to dashboard Cite

show abstract

“…CysC, the APS kinase, then phosphorylates APS to form PAPS. In many bacteria, including M. tuberculosis, cysC is fused in-frame to the 3Ј end of cysN, forming cysNC (32,33). Mycobacterium avium has two highly similar copies of cysN and cysC, one present as cysNC and the other present in unfused form (Fig.…”

Section: Resultsmentioning

confidence: 99%

A sulfated metabolite produced bystf3negatively regulates the virulence ofMycobacteriumtuberculosis

Mougous

Senaratne

Kim

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Sulfated molecules have been shown to modulate isotypic interactions between cells of metazoans and heterotypic interactions between bacterial pathogens or symbionts and their eukaryotic host cells. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces sulfated molecules that have eluded functional characterization for decades. We demonstrate here that a previously uncharacterized sulfated molecule, termed S881, is localized to the outer envelope of M. tuberculosis and negatively regulates the virulence of the organism in two mouse infection models. Furthermore, we show that the biosynthesis of S881 relies on the universal sulfate donor 3 -phosphoadenosine-5 -phosphosulfate and a previously uncharacterized sulfotransferase, stf3. These findings extend the known functions of sulfated molecules as general modulators of cell-cell interactions to include those between a bacterium and a human host.Fourier transform ion cyclotron resonance ͉ hypervirulent ͉ sulfate assimilation ͉ kinase ͉ adenosine-5-phosphosulfate A wide variety of organisms use sulfated molecules to control extracellular events. In mammals, sulfation of tyrosine residues on cell surface proteins is important for the interactions of chemokines with certain chemokine receptors, and for viral binding and entry (1-6). Sulfated glycans modulate processes such as leukocyte homing to lymph nodes, clearance of serum glycoproteins, and blood coagulation (7-9). Members of the glypican family that are modified with sulfated glycosaminoglycans guide organ development in Drosophila by maintaining a morphogen concentration gradient (10).In bacteria, sulfated glycolipids have been shown to serve as extracellular signaling molecules (11). The nitrogen fixing bacterium Sinorhizobium meliloti secretes the nodulation factor NodRm-1, a tetrasaccharide bearing both sulfate and lipid modifications (12). This molecule binds a receptor on the host plant, normally alfalfa, and induces root nodule formation. The sulfate group is critical for the function of NodRm-1, because the unsulfated form fails to induce root nodulation in alfalfa. In the rice blight-causing pathogen Xanthomonas oryzae, several genes involved in the synthesis of sulfated metabolites have been identified as avirulence factors with respect to certain host strains (13,14). These examples suggest that bacterial sulfated metabolites can participate in dialogue with eukaryotic hosts, analogous to their role in mammalian cell-cell communication.Mycobacteria produce an unusually complex array of sulfated structures (11). Sulfolipid-1 (SL-1), an abundant component of the cell envelope of M. tuberculosis, is the best characterized of these molecules. SL-1 has generated much interest because of its elaborate structure and the observation that its abundance correlates with strain virulence (15)(16)(17)(18)(19)(20)(21)(22). Advances in M. tuberculosis genetics and genome sequence data facilitated several contemporary studies that addressed aspects of the biosynthesis and the function of SL-1 in v...

show abstract

“…However, at the 5-h time point this condition resulted in the synthesis or up-regulation of three proteins with potential antioxidant roles, Fe-superoxide dismutase (SodB, decomposition of O 2 · Ϫ ), sulfate adenylyl transferase, and cysteine synthase (CysN and CysK, respectively, which by contributing to cysteine biosynthesis can augment cellular thiol pools). Each of these enzymes is typically up-regulated in bacteria subjected to oxidative stress (9,26,29). It should also be noted that up-regulation of these proteins at the 5-h time point coincides with the partial recovery from chromate stress as reflected by restoration of relatively normal cell morphology (Fig.…”

Section: Vol 188 2006 Effect Of Chromate Stress On E Coli 3375mentioning

confidence: 99%

Effect of Chromate Stress on Escherichia coli K-12

et al. 2006

View full text Add to dashboard Cite

The nature of the stress experienced by Escherichia coli K-12 exposed to chromate, and mechanisms that may enable cells to withstand this stress, were examined. Cells that had been preadapted by overnight growth in the presence of chromate were less stressed than nonadapted controls. Within 3 h of chromate exposure, the latter ceased growth and exhibited extreme filamentous morphology; by 5 h there was partial recovery with restoration of relatively normal cell morphology. In contrast, preadapted cells were less drastically affected in their morphology and growth. Cellular oxidative stress, as monitored by use of an H 2 O 2 -responsive fluorescent dye, was most severe in the nonadapted cells at 3 h postinoculation, lower in the partially recovered cells at 5 h postinoculation, and lower still in the preadapted cells. Chromate exposure depleted cellular levels of reduced glutathione and other free thiols to a greater extent in nonadapted than preadapted cells. In both cell types, the SOS response was activated, and levels of proteins such as SodB and CysK, which can counter oxidative stress, were increased. Some mutants missing antioxidant proteins (SodB, CysK, YieF, or KatE) were more sensitive to chromate. Thus, oxidative stress plays a major role in chromate toxicity in vivo, and cellular defense against this toxicity involves activation of antioxidant mechanisms. As bacterial chromate bioremediation is limited by the toxicity of chromate, minimizing oxidative stress during bacterial chromate reduction and bolstering the capacity of these organisms to deal with this stress will improve their effectiveness in chromate bioremediation.Chromate [Cr(VI)] is a widespread environmental pollutant, as it is a by-product of numerous industrial processes and nuclear weapons production (5). Because chromate is soluble, environmental contamination is difficult to contain. This solubility also promotes the active transport of chromate across biological membranes (7), and once internalized by cells, Cr(VI) exhibits a variety of toxic, mutagenic, and carcinogenic effects (34, 44). In contrast, most cells are impermeable to Cr(III), which is insoluble under typical environmental conditions (30); as measured by the Ames test, it is therefore some 1,000-fold less mutagenic than Cr(VI) (19). Thus, strategies for decontamination of environmental chromate focus on reducing it to Cr(III). Chemical methods for this are prohibitively expensive for large-scale environmental application and frequently have damaging consequences of their own (7), and so bacterial bioremediation is of considerable interest as an environmentally friendly and affordable solution to chromate pollution.Several bacteria, including Escherichia coli, Shewanella oneidensis, and numerous species of Pseudomonas and Bacillus, can reduce Cr(VI) to Cr(III) (17, 39); nonetheless, an effective bacterial system for in situ reduction has not yet been developed. One reason is that chromate is also toxic to the remediating bacteria (17). Our in vitro studies have strongly i...

show abstract

The Mycobacterium tuberculosis cysD and cysNC genes form a stress-induced operon that encodes a tri-functional sulfate-activating complex

Cited by 81 publications

References 27 publications

A Two-Component Regulatory System Integrates Redox State and Population Density Sensing in Pseudomonas putida

A Two-Component Regulatory System Integrates Redox State and Population Density Sensing in Pseudomonas putida

A sulfated metabolite produced bystf3negatively regulates the virulence ofMycobacteriumtuberculosis

Effect of Chromate Stress on Escherichia coli K-12

Contact Info

Product

Resources

About