scholarly journals Global transcriptional response to vancomycin in Mycobacterium tuberculosis

Microbiology ◽  
2009 ◽  
Vol 155 (4) ◽  
pp. 1093-1102 ◽  
Author(s):  
Roberta Provvedi ◽  
Francesca Boldrin ◽  
Francesco Falciani ◽  
Giorgio Palù ◽  
Riccardo Manganelli
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Surface Stress ◽  
Sigma Factor ◽  
Clustering Analysis ◽  
Transcriptional Response ◽  
Alternative Sigma Factor ◽  
Hierarchical Clustering Analysis ◽  
Physiological Mechanisms ◽  
Basal Resistance ◽  
Antibacterial Drugs

In order to gain additional understanding of the physiological mechanisms used by bacteria to maintain surface homeostasis and to identify potential targets for new antibacterial drugs, we analysed the variation of the Mycobacterium tuberculosis transcriptional profile in response to inhibitory and subinhibitory concentrations of vancomycin. Our analysis identified 153 genes differentially regulated after exposing bacteria to a concentration of the drug ten times higher than the MIC, and 141 genes differentially expressed when bacteria were growing in a concentration of the drug eightfold lower than the MIC. Hierarchical clustering analysis indicated that the response to these different conditions is different, although with some overlap. This approach allowed us to identify several genes whose products could be involved in the protection from antibiotic stress targeting the envelope and help to confer the basal level of M. tuberculosis resistance to antibacterial drugs, such as Rv2623 (UspA-like), Rv0116c, PE20-PPE31, PspA and proteins related to toxin–antitoxin systems. Moreover, we also demonstrated that the alternative sigma factor σ E confers basal resistance to vancomycin, once again underlining its importance in the physiology of the mycobacterial surface stress response.

scholarly journals Mycobacterium tuberculosis virulence-regulator PhoP interacts with alternative sigma factor SigE during acid-stress response

2017 ◽  
Vol 104 (3) ◽  
pp. 400-411 ◽  
Author(s):  
Roohi Bansal ◽  
Vijjamarri Anil Kumar ◽  
Ritesh Rajesh Sevalkar ◽  
Prabhat Ranjan Singh ◽  
Dibyendu Sarkar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Stress Response ◽  
Sigma Factor ◽  
Acid Stress ◽  
Alternative Sigma Factor ◽  
Acid Stress Response ◽  
Virulence Regulator

scholarly journals Characterisation of the Mycobacterium tuberculosis alternative sigma factor SigG: Its operon and regulon

Tuberculosis ◽  
2013 ◽  
Vol 93 (5) ◽  
pp. 482-491 ◽  
Author(s):  
Alison Gaudion ◽  
Lisa Dawson ◽  
Elaine Davis ◽  
Katherine Smollett
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sigma Factor ◽  
Alternative Sigma Factor

scholarly journals Transcription Regulation by the Mycobacterium tuberculosis Alternative Sigma Factor SigD and Its Role in Virulence

2004 ◽  
Vol 186 (19) ◽  
pp. 6605-6616 ◽  
Author(s):  
Sahadevan Raman ◽  
Rohan Hazra ◽  
Christopher C. Dascher ◽  
Robert N. Husson
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Unknown Function ◽  
Sigma Factor ◽  
Regulation Of Gene Expression ◽  
Large Family ◽  
Promoter Sequence ◽  
Infection Model ◽  
Alternative Sigma Factor

ABSTRACT Mycobacterium tuberculosis, an obligate mammalian pathogen, adapts to its host during the course of infection via the regulation of gene expression. Of the regulators of transcription that play a role in this response, several alternative sigma factors of M. tuberculosis have been shown to control gene expression in response to stresses, and some of these are required for virulence or persistence in vivo. For this study, we examined the role of the alternative sigma factor SigD in M. tuberculosis gene expression and virulence. Using microarray analysis, we identified several genes whose expression was altered in a strain with a sigD deletion. A small number of these genes, including sigD itself, the gene encoding the autocrine growth factor RpfC, and a gene of unknown function, Rv1815, appear to be directly regulated by this sigma factor. By identifying the in vivo promoters of these genes, we have determined a consensus promoter sequence that is putatively recognized by SigD. The expression of several genes encoding PE-PGRS proteins, part of a large family of related genes of unknown function, was significantly increased in the sigD mutant. We found that the expression of sigD is stable throughout log phase and stationary phase but that it declines rapidly with oxygen depletion. In a mouse infection model, the sigD mutant strain was attenuated, with differences in survival and the inflammatory response in the lung between mice infected with the mutant and those infected with the wild type.

scholarly journals The Alternative Sigma Factor SigH Regulates Major Components of Oxidative and Heat Stress Responses in Mycobacterium tuberculosis

2001 ◽  
Vol 183 (20) ◽  
pp. 6119-6125 ◽  
Author(s):  
Sahadevan Raman ◽  
Taeksun Song ◽  
Xiaoling Puyang ◽  
Stoyan Bardarov ◽  
William R. Jacobs ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mycobacterium Tuberculosis ◽  
Heat Stress ◽  
Heat Shock ◽  
Stress Responses ◽  
Sigma Factor ◽  
Inducible Expression ◽  
Alternative Sigma Factor ◽  
And Oxidative Stress

ABSTRACT Mycobacterium tuberculosis is a specialized intracellular pathogen that must regulate gene expression to overcome stresses produced by host defenses during infection. SigH is an alternative sigma factor that we have previously shown plays a role in the response to stress of the saprophyte Mycobacterium smegmatis. In this work we investigated the role ofsigH in the M.tuberculosis response to heat and oxidative stress. We determined that a M. tuberculosis sigHmutant is more susceptible to oxidative stresses and that the inducible expression of the thioredoxin reductase/thioredoxin genestrxB2/trxC and a gene of unknown function, Rv2466c, is regulated by sigH via expression from promoters directly recognized by SigH. We also determined that thesigH mutant is more susceptible to heat stress and that inducible expression of the heat shock genes dnaK andclpB is positively regulated by sigH. The induction of these heat shock gene promoters but not of other SigH-dependent promoters was markedly greater in response to heat versus oxidative stress, consistent with their additional regulation by a heat-labile repressor. To further understand the role ofsigH in the M.tuberculosis stress response, we investigated the regulation of the stress-responsive sigma factor genessigE and sigB. We determined that inducible expression of sigE is regulated bysigH and that basal and inducible expression ofsigB is dependent on sigE andsigH. These data indicate that sigH plays a central role in a network that regulates heat and oxidative-stress responses that are likely to be important in M.tuberculosis pathogenesis.

scholarly journals Mycobacterium tuberculosis Binds Human Serum Amyloid A and the Interaction Modulates the Colonization of Human Macrophages and the Transcriptional Response of the Pathogen

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1264
Author(s):  
Malwina Kawka ◽  
Anna Brzostek ◽  
Katarzyna Dzitko ◽  
Jakub Kryczka ◽  
Radosław Bednarek ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Serum Amyloid A ◽  
Acute Phase Protein ◽  
Transcriptional Response ◽  
Serum Amyloid ◽  
Host Protein ◽  
Binding Interaction ◽  
Human Macrophages ◽  
Amyloid A ◽  
Transporter Systems

As a very successful pathogen with outstanding adaptive properties, Mycobacterium tuberculosis (Mtb) has developed a plethora of sophisticated mechanisms to subvert host defenses and effectively enter and replicate in the harmful environment inside professional phagocytes, namely, macrophages. Here, we demonstrated the binding interaction of Mtb with a major human acute phase protein, namely, serum amyloid A (SAA1), and identified AtpA (Rv1308), ABC (Rv2477c), EspB (Rv3881c), TB 18.6 (Rv2140c), and ThiC (Rv0423c) membrane proteins as mycobacterial effectors responsible for the pathogen-host protein interplay. SAA1-opsonization of Mtb prior to the infection of human macrophages favored bacterial entry into target phagocytes accompanied by a substantial increase in the load of intracellularly multiplying and surviving bacteria. Furthermore, binding of human SAA1 by Mtb resulted in the up- or downregulation of the transcriptional response of tubercle bacilli. The most substantial changes were related to the increased expression level of the genes of two operons encoding mycobacterial transporter systems, namely, mmpL5/mmpS5 (rv0676c), and rv1217c, rv1218c. Therefore, we postulate that during infection, Mtb-SAA1 binding promotes the infection of host macrophages by tubercle bacilli and modulates the functional response of the pathogen.

scholarly journals Moxifloxacin Activates the SOS Response in Mycobacterium tuberculosis in a Dose- and Time-Dependent Manner

2021 ◽  
Vol 9 (2) ◽  
pp. 255
Author(s):  
Angelo Iacobino ◽  
Giovanni Piccaro ◽  
Manuela Pardini ◽  
Lanfranco Fattorini ◽  
Federico Giannoni
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Physiological State ◽  
Transcriptional Response ◽  
Sos Response ◽  
Resistant Mutant ◽  
Time Dependent ◽  
Dependent Manner ◽  
Gyra Gene ◽  
Drug Concentrations

Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium tuberculosis. Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, recA, lexA, dnaE2, Rv3074 and Rv3776, were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced recA, with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of recA by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gyrA gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the relK toxin and of Rv3290c and Rv2517c, two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.

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