scholarly journals Lipid composition and transcriptional response of Mycobacterium tuberculosis grown under iron-limitation in continuous culture: identification of a novel wax ester

Microbiology ◽  
2007 ◽  
Vol 153 (5) ◽  
pp. 1435-1444 ◽  
Author(s):  
Joanna Bacon ◽  
Lynn G Dover ◽  
Kim A Hatch ◽  
Yi Zhang ◽  
Jessica M Gomes ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Continuous Culture ◽  
Lipid Composition ◽  
Transcriptional Response ◽  
Iron Limitation ◽  
Wax Ester ◽  
Culture Identification

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.

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 Wax Ester Synthesis is Required for Mycobacterium tuberculosis to Enter In Vitro Dormancy

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e51641 ◽  
Author(s):  
Tatiana D. Sirakova ◽  
Chirajyoti Deb ◽  
Jaiyanth Daniel ◽  
Harminder D. Singh ◽  
Hedia Maamar ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Wax Ester ◽  
Ester Synthesis

scholarly journals Signature required: The transcriptional response to tuberculosis

2021 ◽  
Vol 218 (12) ◽  
Author(s):  
Clifton E. Barry ◽  
Katrin D. Mayer-Barber
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Symptoms ◽  
Transcriptional Response

The majority of humans infected with Mycobacterium tuberculosis never experience clinical symptoms or signs, but predicting those who will remains out of reach. Here, we discuss recent studies that reveal patterns and pathways that determine who is at highest risk for progression.

scholarly journals Alveolar macrophages generate a noncanonical NRF2-driven transcriptional response to Mycobacterium tuberculosis in vivo

2019 ◽  
Vol 4 (37) ◽  
pp. eaaw6693 ◽  
Author(s):  
Alissa C. Rothchild ◽  
Gregory S. Olson ◽  
Johannes Nemeth ◽  
Lynn M. Amon ◽  
Dat Mai ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Alveolar Macrophages ◽  
Adaptive Immune Response ◽  
Transcriptional Response ◽  
Enrichment Analysis ◽  
Macrophage Response ◽  
In Vitro Systems

Alveolar macrophages (AMs) are the first cells to be infected during Mycobacterium tuberculosis (M.tb.) infection. Thus, the AM response to infection is the first of many steps leading to initiation of the adaptive immune response required for efficient control of infection. A hallmark of M.tb. infection is the slow initiation of the adaptive response, yet the mechanisms responsible for this are largely unknown. To study the initial AM response to infection, we developed a system to identify, sort, and analyze M.tb.-infected AMs from the lung within the first 10 days of infection. In contrast to what has been previously described using in vitro systems, M.tb.-infected AMs up-regulate a cell-protective antioxidant transcriptional signature that is dependent on the lung environment but not bacterial virulence. Computational approaches including pathway analysis and transcription factor motif enrichment analysis identify NRF2 as a master regulator of the response. Using knockout mouse models, we demonstrate that NRF2 drives expression of the cell-protective signature in AMs and impairs the control of early bacterial growth. AMs up-regulate a substantial pro-inflammatory response to M.tb. infection only 10 days after infection, yet comparisons with bystander AMs from the same infected animals demonstrate that M.tb.-infected AMs generate a less robust inflammatory response than the uninfected cells around them. Our findings demonstrate that the initial macrophage response to M.tb. in the lung is far less inflammatory than has previously been described by in vitro systems and may impede the overall host response to infection.

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