scholarly journals Critical Role of a Single Position in the −35 Element for Promoter Recognition by Mycobacterium tuberculosis SigE and SigH

2008 ◽  
Vol 190 (6) ◽  
pp. 2227-2230 ◽  
Author(s):  
Taeksun Song ◽  
Seung-Eun Song ◽  
Sahadevan Raman ◽  
Mauricio Anaya ◽  
Robert N. Husson
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Role ◽  
Primer Extension ◽  
Promoter Recognition

ABSTRACT Mycobacterial SigE and SigH both initiate transcription from the sigB promoter, suggesting that they recognize similar sequences. Through mutational and primer extension analyses, we determined that SigE and SigH recognize nearly identical promoters, with differences at the 3′ end of the −35 element distinguishing between SigE- and SigH-dependent promoters.

scholarly journals Metabolic Switching of Mycobacterium tuberculosis during Hypoxia Is Controlled by the Virulence Regulator PhoP

2020 ◽  
Vol 202 (7) ◽  
Author(s):  
Prabhat Ranjan Singh ◽  
Anil Kumar Vijjamarri ◽  
Dibyendu Sarkar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nitrogen Metabolism ◽  
Electron Acceptor ◽  
Latent Infection ◽  
Critical Role ◽  
Hypoxic Stress ◽  
Content Type ◽  
Metabolic Switching ◽  
Virulence Regulator

ABSTRACT Mycobacterium tuberculosis retains the ability to establish an asymptomatic latent infection. A fundamental question in mycobacterial physiology is to understand the mechanisms involved in hypoxic stress, a critical player in persistence. Here, we show that the virulence regulator PhoP responds to hypoxia, the dormancy signal, and effectively integrates hypoxia with nitrogen metabolism. We also provide evidence to demonstrate that both under nitrogen limiting conditions and during hypoxia, phoP locus controls key genes involved in nitrogen metabolism. Consistently, under hypoxia a ΔphoP strain shows growth attenuation even with surplus nitrogen, the alternate electron acceptor, and complementation of the mutant restores bacterial growth. Together, our observations provide new biological insights into the role of PhoP in integrating nitrogen metabolism with hypoxia by the assistance of the hypoxia regulator DosR. The results have significant implications on the mechanism of intracellular survival and growth of the tubercle bacilli under a hypoxic environment within the phagosome. IMPORTANCE M. tuberculosis retains the unique ability to establish an asymptomatic latent infection. To understand the mechanisms involved in hypoxic stress which play a critical role in persistence, we show that the virulence regulator PhoP is linked to hypoxia, the dormancy signal. In keeping with this, phoP was shown to play a major role in M. tuberculosis growth under hypoxia even in the presence of surplus nitrogen, the alternate electron acceptor. Our results showing regulation of hypoxia-responsive genes provide new biological insights into role of the virulence regulator in metabolic switching by sensing hypoxia and integrating nitrogen metabolism with hypoxia by the assistance of the hypoxia regulator DosR.

scholarly journals Critical role of amino acid position 343 of surfactant protein-D in the selective binding of glycolipids from Mycobacterium tuberculosis

Glycobiology ◽  
2009 ◽  
Vol 19 (12) ◽  
pp. 1473-1484 ◽  
Author(s):  
Tracy K Carlson ◽  
Jordi B Torrelles ◽  
Kelly Smith ◽  
Tim Horlacher ◽  
Riccardo Castelli ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
Critical Role ◽  
Amino Acid Position ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Selective Binding

scholarly journals Metabolic switching of Mycobacterium tuberculosis during hypoxia is controlled by the virulence regulator PhoP

2019 ◽  
Author(s):  
Prabhat Ranjan Singh ◽  
Vijjamarri Anil Kumar ◽  
Dibyendu Sarkar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nitrogen Metabolism ◽  
Electron Acceptor ◽  
Latent Infection ◽  
Critical Role ◽  
Hypoxic Stress ◽  
Metabolic Switching ◽  
Virulence Regulator ◽  
Unique Ability

ABSTRACTMycobacterium tuberculosis (Mtb) retains the unique ability to establish an asymptomatic latent infection. A fundamental question in mycobacterial physiology is to understand the mechanisms involved in hypoxic stress, a critical player in persistence. Here, we show that the virulence regulator PhoP responds to hypoxia, the dormancy signal and effectively integrates hypoxia with nitrogen metabolism. We also provide evidence to demonstrate that both under nitrogen limiting conditions and during hypoxia, phoP locus controls key genes involved in nitrogen metabolism. Consistently, under hypoxia ΔphoP shows growth attenuation even with surplus nitrogen, the alternate electron acceptor, and complementation of the mutant restores bacterial growth. Together, our observations provide new biological insights into the role of PhoP in integrating nitrogen metabolism with hypoxia by the assistance of the hypoxia regulator DosR. The results have significant implications on the mechanism of intracellular survival and growth of the tubercle bacilli under a hypoxic environment within the phagosome.ImportanceMtb retains the unique ability to establish an asymptomatic latent infection. To understand the mechanisms involved in hypoxic stress which plays a critical role in persistence, we show that the virulence regulator PhoP responds to hypoxia, the dormancy signal. In keeping with this, phoP was shown to play a major role in Mtb growth under hypoxia even in presence of surplus nitrogen, the alternate electron acceptor. Our results showing regulation of hypoxia-responsive genes provide new biological insights into role of the virulence regulator in metabolic switching by sensing hypoxia and integrating nitrogen metabolism with hypoxia by the assistance of the hypoxia regulator DosR.

scholarly journals New Aspects in Immunopathology of Mycobacterium tuberculosis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
E. Mortaz ◽  
M. Varahram ◽  
P. Farnia ◽  
M. Bahadori ◽  
MR Masjedi
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Mycobacterium Tuberculosis ◽  
Critical Role ◽  
Etiologic Agent ◽  
Innate Immune ◽  
Major Health Problem ◽  
Lectin Receptors ◽  
Host Interactions

Our understanding of tuberculosis (TB) pathology and immunology has become extensively deeper and more refined since the identification of Mycobacterium tuberculosis (MTB) as the etiologic agent of disease by Dr. Robert Koch in 1882. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. TB, caused by MTB, is a major health problem in world, with 10 million new cases diagnosed each year. Innate immunity is shown playing an important role in the host defense against the MTB, and the first step in this process is recognition of MTB by cells of the innate immune system. Several classes of pattern recognition receptors (PPRs) are involved in the recognition of MTB, including toll-like receptors (TLRs), C-type lectin receptors (CLRs), and nod-like receptors (NLRs). Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down streams, proteins play the most prominent roles in the initiation of the immune response against MTB. Beside of TLRs signaling, recently the activation of inflammasome pathway in the pathogenesis of TB much appreciated. Knowledge about these signaling pathways is crucial for understanding the pathophysiology of TB, on one hand, and for the development of novel strategies of vaccination and treatment such as immunotherapy on the other. Given the critical role of TLRs/inflammasome signaling in innate immunity and initiation of the appropriate adaptive response, the regulation of these pathways is likely to be an important determinant of the clinical outcome of MTB infection. In this review paper we focused on the immune response, which is the recognition of MTB by inflammatory innate immune cells following infection.

scholarly journals Role of Stress Response Sigma Factor SigG in Mycobacterium tuberculosis

2007 ◽  
Vol 190 (3) ◽  
pp. 1128-1133 ◽  
Author(s):  
Jong-Hee Lee ◽  
Deborah E. Geiman ◽  
William R. Bishai
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type Strain ◽  
Wild Type Strain ◽  
Sos Response ◽  
Wild Type ◽  
Recognition Sequence ◽  
Reverse Transcription Pcr ◽  
Promoter Recognition ◽  
Microarray Studies

ABSTRACT The sigG gene of Mycobacterium tuberculosis was disrupted by homologous recombination, and the genes regulated by SigG were examined by real-time reverse-transcription PCR and microarray studies. The SigG consensus promoter recognition sequence was identified as GCGNGT-N15-18-CGANCA. A ΔsigG mutant was found to be more resistant to mitomycin C treatment than the wild-type strain, indicating that it may be involved in the SOS response in M. tuberculosis.

scholarly journals Critical role of AIM2 in Mycobacterium tuberculosis infection

2012 ◽  
Vol 24 (10) ◽  
pp. 637-644 ◽  
Author(s):  
H. Saiga ◽  
S. Kitada ◽  
Y. Shimada ◽  
N. Kamiyama ◽  
M. Okuyama ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Role ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection

scholarly journals Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations.

1997 ◽  
Vol 41 (8) ◽  
pp. 1677-1681 ◽  
Author(s):  
S Sreevatsan ◽  
K E Stockbauer ◽  
X Pan ◽  
B N Kreiswirth ◽  
S L Moghazeh ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
Amino Acid Residue ◽  
Critical Role ◽  
Polymorphism Analysis ◽  
Nucleotide Substitutions ◽  
Automated Dna Sequencing ◽  
Resistant Strains ◽  
Conformation Polymorphism

Ethambutol [(S,S')-2,2'-(ethylenediimino)di-1-butanol; EMB], is a first-line drug used to treat tuberculosis. To gain insight into the molecular basis of EMB resistance, we characterized the 10-kb embCAB locus in 16 EMB-resistant and 3 EMB-susceptible genetically distinct Mycobacterium tuberculosis strains from diverse localities by automated DNA sequencing and single-stranded conformation polymorphism analysis. All 19 organisms had virtually identical sequences for the entire 10-kb region. Eight EMB-resistant organisms had mutations located in codon 306 of embB that resulted in the replacement of the wild-type Met residue with Ile or Val. Automated sequence analysis of the 5' region (1,892 bp) of embB in an additional 69 EMB-resistant and 30 EMB-susceptible M. tuberculosis isolates from diverse geographic localities and representing 70 distinct IS6110 fingerprints confirmed the unique association of substitutions in amino acid residue 306 of EmbB with EMB resistance. Six other embB nucleotide substitutions resulting in four amino acid replacements were uniquely found in resistant strains. Sixty-nine percent of epidemiologically unassociated EMB-resistant organisms had an amino acid substitution not found in susceptible strains, and most (89%) replacements occurred at amino acid residue 306 of EmbB. For strains with the Met306Leu or Met306Val replacements EMB MICs were generally higher (40 microg/ml) than those for organisms with Met306Ile substitutions (20 microg/ml). The data are consistent with the idea that amino acid substitutions in EmbB alter the drug-protein interaction and thereby cause EMB resistance.

Critical role of TRIF and MyD88 in Mycobacterium tuberculosis Hsp70-mediated activation of dendritic cells

Cytokine ◽  
2015 ◽  
Vol 71 (2) ◽  
pp. 139-144 ◽  
Author(s):  
Tae-Hyoun Kim ◽  
Sung Jae Shin ◽  
Yeong-Min Park ◽  
In Duk Jung ◽  
Seung-Wook Ryu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Critical Role

scholarly journals Critical Role of Toll-Like Receptor 9 in Morphine and Mycobacterium tuberculosis–Induced Apoptosis in Mice

PLoS ONE ◽  
2010 ◽  
Vol 5 (2) ◽  
pp. e9205 ◽  
Author(s):  
Lin Chen ◽  
Wanliang Shi ◽  
Hui Li ◽  
Xiuli Sun ◽  
Xionglin Fan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Role ◽  
Toll Like Receptor ◽  
Induced Apoptosis

scholarly journals The Critical Role of embC in Mycobacterium tuberculosis

2008 ◽  
Vol 190 (12) ◽  
pp. 4335-4341 ◽  
Author(s):  
Renan Goude ◽  
Anita G. Amin ◽  
Delphi Chatterjee ◽  
Tanya Parish
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Essential Gene ◽  
Critical Role ◽  
Normal Growth ◽  
Growth Conditions ◽  
Northern Analysis ◽  
Immunomodulatory Effects ◽  
Key Genes

ABSTRACT Arabinan polymers are major components of the cell wall in Mycobacterium tuberculosis and are involved in maintaining its structure, as well as playing a role in host-pathogen interactions. In particular, lipoarabinomannan (LAM) has multiple immunomodulatory effects. In the nonpathogenic species Mycobacterium smegmatis, EmbC has been identified as a key arabinosyltransferase involved in the incorporation of arabinose into LAM, and an embC mutant is viable but lacks LAM. In contrast, we demonstrate here that in M. tuberculosis, embC is an essential gene under normal growth conditions, suggesting a more crucial role for LAM in the pathogenic mycobacteria. M. tuberculosis EmbC has an activity similar to that of M. smegmatis EmbC, since we were able to complement an embC mutant of M. smegmatis with embCMtb , confirming that it encodes a functional arabinosyltransferase. In addition, we observed that the size of LAM produced in M. smegmatis was dependent on the level of expression of embCMtb . Northern analysis revealed that embC is expressed as part of a polycistronic message encompassing embC and three upstream genes. The promoter region for this transcript was identified and found to be up-regulated in stationary phase but down-regulated during hypoxia-induced nonreplicating persistence. In conclusion, we have identified one of the key genes involved in LAM biosynthesis in M. tuberculosis and confirmed its essential role in this species.

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