Role of two‐component regulatory systems in intracellular survival of Mycobacterium tuberculosis

2019 ◽  
Vol 120 (8) ◽  
pp. 12197-12207
Author(s):  
Xue Li ◽  
Xi Lv ◽  
Yanping Lin ◽  
Junfeng Zhen ◽  
Cao Ruan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Intracellular Survival ◽  
Regulatory Systems ◽  
Two Component

The role of two-component regulatory systems in environmental sensing and virulence in Salmonella

2021 ◽  
pp. 1-38
Author(s):  
Lucindo Cardoso de Pina ◽  
Fernanda Stephens Hermes da Silva ◽  
Teca Calcagno Galvão ◽  
Heidi Pauer ◽  
Rosana Barreto Rocha Ferreira ◽  
...  
Keyword(s):  
Environmental Sensing ◽  
Regulatory Systems ◽  
Two Component

Rv2223c, an acid inducible carboxyl-esterase of Mycobacterium tuberculosis enhanced the growth and survival of Mycobacterium smegmatis

2019 ◽  
Vol 14 (16) ◽  
pp. 1397-1415
Author(s):  
Pratibha Maan ◽  
Jagdeep Kaur
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Intracellular Survival ◽  
Growth And Survival ◽  
Enhanced Expression ◽  
Stress Environment ◽  
In Vitro Stress ◽  
Carboxyl Esterase

Aim: To elucidate the role of Rv2223c in Mycobacterium tuberculosis. Methods: Purified recombinant Rv2223c protein was characterized. Expression of rv2223c in the presence of different stress environment and subcellular localization were performed in M. tuberculosis H37Ra and Mycobacterium smegmatis ( MS_2223c). Effect of its overexpression on growth rate, infection and intracellular survival in THP-1/PBMC cells were studied. Results: rRv2223c demonstrated esterase activity with preference for pNP-octanoate and hydrolyzed trioctanoate to di- and mono-octanoate. Expression of rv2223c was upregulated in acidic and nutritive stress conditions. rRv2223c was identified in extracellular and cell wall fractions. MS_2223c exhibited enhanced growth, survival during in vitro stress, infection and intracellular survival. Conclusions: Rv2223c is a secretary, carboxyl-esterase, with enhanced expression under acidic and nutritive stress condition and might help in intracellular survival of bacteria.

scholarly journals The role of two-component systems in the physiology of Mycobacterium tuberculosis

IUBMB Life ◽  
2018 ◽  
Vol 70 (8) ◽  
pp. 710-717 ◽  
Author(s):  
Manikuntala Kundu
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

scholarly journals Differential regulation of the two-component regulatory system senX3-regX3 in Mycobacterium tuberculosis

Microbiology ◽  
2014 ◽  
Vol 160 (6) ◽  
pp. 1125-1133 ◽  
Author(s):  
Dalin Rifat ◽  
Petros C. Karakousis
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Promoter Activity ◽  
Regulatory System ◽  
Differential Regulation ◽  
Northern Analysis ◽  
Pcr Analysis ◽  
Reporter System ◽  
Two Component ◽  
Phosphate Depletion

The highly successful pathogen Mycobacterium tuberculosis (Mtb) has evolved strategies to adapt to various stress conditions, thus promoting survival within the infected host. The two-component regulatory system (2CRS) senX3-regX3, which has been implicated in the Mtb response to inorganic phosphate depletion, is believed to behave as an auto-regulatory bicistronic operon. Unlike other 2CRS, Mtb senX3-regX3 features an intergenic region (IR) containing several mycobacterium interspersed repetitive units (MIRU) of unknown function. In this study, we used a lacZ reporter system to study the promoter activity of the 5′ untranslated region of senX3, and that of various numbers of MIRUs in the senX3-regX3 IR, during axenic Mtb growth in nutrient-rich broth, and upon exposure to growth-restricting conditions. Activity of the senX3 promoter was induced during phosphate depletion and nutrient starvation, and IR promoter activity under these conditions was directly proportional to the number of MIRUs present. Quantitative reverse transcriptase (qRT)-PCR analysis of exponentially growing Mtb revealed monocistronic transcription of senX3 and regX3, and, to a lesser degree, bicistronic transcription of the operon. In addition, we observed primarily monocistronic upregulation of regX3 during phosphate depletion of Mtb, which was confirmed by Northern analysis in wild-type Mtb and by RT-PCR in a senX3-disrupted mutant, while upregulation of regX3 in nutrient-starved Mtb was chiefly bicistronic. Our findings of differential regulation of senX3-regX3 highlight the potential regulatory role of MIRUs in the Mtb genome and provide insight into the regulatory mechanisms underlying Mtb adaptation to physiologically relevant conditions.

scholarly journals Yersinia pestis Two-Component Gene Regulatory Systems Promote Survival in Human Neutrophils

2009 ◽  
Vol 78 (2) ◽  
pp. 773-782 ◽  
Author(s):  
Jason L. O'Loughlin ◽  
Justin L. Spinner ◽  
Scott A. Minnich ◽  
Scott D. Kobayashi
Keyword(s):  
Immune System ◽  
Yersinia Pestis ◽  
Innate Immune System ◽  
Intracellular Survival ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Regulatory Systems ◽  
Two Component ◽  
Gene Regulatory ◽  
Component Gene

ABSTRACT Human polymorphonuclear leukocytes (PMNs, or neutrophils) are the most abundant innate immune cell and kill most invading bacteria through combined activities of reactive oxygen species (ROS) and antimicrobial granule constituents. Pathogens such as Yersinia pestis resist destruction by the innate immune system and are able to survive in macrophages and neutrophils. The specific molecular mechanisms used by Y. pestis to survive following phagocytosis by human PMNs are incompletely defined. To gain insight into factors that govern Y. pestis intracellular survival in neutrophils, we inactivated 25 two-component gene regulatory systems (TCSs) with known or inferred function and assessed susceptibility of these mutant strains to human PMN granule extracts. Y. pestis strains deficient for PhoPQ, KdpED, CheY, CvgSY, and CpxRA TCSs were selected for further analysis, and all five strains were altered for survival following interaction with PMNs. Of these five strains, only Y. pestis ΔphoPQ demonstrated global sensitivity to a panel of seven individual neutrophil antimicrobial peptides and serine proteases. Notably, Y. pestis ΔphoPQ was deficient for intracellular survival in PMNs. Iterative analysis with Y. pestis strains lacking the PhoP-regulated genes ugd and pmrK indicated that the mechanism most likely responsible for increased resistance to killing is 4-amino-4-deoxy-l-arabinose modification of lipid A. Together, the data provide new information about Y. pestis evasion of the innate immune system.

scholarly journals Deletion of Two-Component Regulatory Systems Increases the Virulence of Mycobacterium tuberculosis

2003 ◽  
Vol 71 (3) ◽  
pp. 1134-1140 ◽  
Author(s):  
Tanya Parish ◽  
Debbie A. Smith ◽  
Sharon Kendall ◽  
Nicola Casali ◽  
Gregory J. Bancroft ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Acute Stage ◽  
Wild Type ◽  
Regulatory Systems ◽  
Two Component ◽  
Scid Mouse Model ◽  
Two Component Systems ◽  
Immunocompetent Mice ◽  
Host Killing

ABSTRACT Two-component regulatory signal transduction systems are widely distributed among bacteria and enable the organisms to make coordinated changes in gene expression in response to a variety of environmental stimuli. The genome sequence of Mycobacterium tuberculosis contains 11 complete two-component systems, four isolated homologous regulators, and three isolated homologous sensors. We have constructed defined mutations in six of these genes and measured virulence in a SCID mouse model. Mice infected with four of the mutants (deletions of devR, tcrXY, trcS, and kdpDE) died more rapidly than those infected with wild-type bacteria. The other two mutants (narL and Rv3220c) showed no change compared to the wild-type H37Rv strain. The most hypervirulent mutant (devRΔ) also grew more rapidly in the acute stage of infection in immunocompetent mice and in gamma interferon-activated macrophages. These results define a novel class of genes in this pathogen whose presence slows down its multiplication in vivo or increases its susceptibility to host killing mechanisms. Thus, M. tuberculosis actively maintains a balance between its own survival and that of the host.

scholarly journals Role of Two Novel Two-Component Regulatory Systems in Development and Phosphatase Expression in Myxococcus xanthus

2003 ◽  
Vol 185 (4) ◽  
pp. 1376-1383 ◽  
Author(s):  
Aurelio Moraleda-Muñoz ◽  
Juana Carrero-Lérida ◽  
Juana Pérez ◽  
José Muñoz-Dorado
Keyword(s):  
Response Regulator ◽  
Myxococcus Xanthus ◽  
Regulatory System ◽  
Response Regulators ◽  
Helix Loop Helix ◽  
Double Deletion ◽  
Regulatory Systems ◽  
Two Component ◽  
Single Deletion

ABSTRACT We have cloned a two-component regulatory system (phoR2-phoP2) of Myxococcus xanthus while searching for genes that encode proteins with phosphatase activity, where phoR2 encodes the histidine kinase and phoP2 encodes the response regulator. A second system, phoR3-phoP3, was identified and isolated by using phoP2 as a probe. These two systems are quite similar, sharing identities along the full-length proteins of 52% on the histidine kinases and 64% on the response regulators. The predicted structures of both kinases suggest that they are anchored to the membrane, with the sensor domains being located in the periplasmic space and the kinase domains in the cytoplasm. The response regulators (PhoP2 and PhoP3) exhibit a helix-loop-helix motif typical of DNA-binding proteins in the effector domains located in the C-terminal region. Studies on two single-deletion mutants and one double-deletion mutant have revealed that these systems are involved in development. Mutant fruiting bodies are not well packed, originating loose and flat aggregates where some myxospores do not reshape properly, and they remain as elongated cells. These systems are also involved in the expression of Mg-independent acid and neutral phosphatases, which are expressed during development. The neutral phosphatase gene is especially dependent on PhoP3. Neither PhoP2 nor PhoP3 regulates the expression of alkaline phosphatases and the pph1 gene.

scholarly journals Role of two-component regulatory systems in the virulence of Streptococcus suis

2018 ◽  
Vol 214 ◽  
pp. 123-128 ◽  
Author(s):  
Chengkun Zheng ◽  
Lingzhi Li ◽  
Haojie Ge ◽  
Hongmei Meng ◽  
Yang Li ◽  
...  
Keyword(s):  
Streptococcus Suis ◽  
Regulatory Systems ◽  
Two Component

scholarly journals Polymyxin Resistance ofPseudomonas aeruginosa phoQMutants Is Dependent on Additional Two-Component Regulatory Systems

2013 ◽  
Vol 57 (5) ◽  
pp. 2204-2215 ◽  
Author(s):  
Alina D. Gutu ◽  
Nicole Sgambati ◽  
Pnina Strasbourger ◽  
Mark K. Brannon ◽  
Michael A. Jacobs ◽  
...  
Keyword(s):  
Lipid A ◽  
Regulatory System ◽  
Content Type ◽  
Regulatory Systems ◽  
Clinical Resistance ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
High Level

ABSTRACTPseudomonas aeruginosacan develop resistance to polymyxin as a consequence of mutations in the PhoPQ regulatory system, mediated by covalent lipid A modification. Transposon mutagenesis of a polymyxin-resistantphoQmutant defined 41 novel loci required for resistance, including two regulatory systems, ColRS and CprRS. Deletion of thecolRSgenes, individually or in tandem, abrogated the polymyxin resistance of a ΔphoQmutant, as did individual or tandem deletion ofcprRS. Individual deletion ofcolRorcolSin a ΔphoQmutant also suppressed 4-amino-l-arabinose addition to lipid A, consistent with the known role of this modification in polymyxin resistance. Surprisingly, tandem deletion ofcolRSorcprRSin the ΔphoQmutant or individual deletion ofcprRorcprSfailed to suppress 4-amino-l-arabinose addition to lipid A, indicating that this modification alone is not sufficient for PhoPQ-mediated polymyxin resistance inP. aeruginosa. Episomal expression ofcolRSorcprRSin tandem or ofcprRindividually complemented the Pm resistance phenotype in the ΔphoQmutant, while episomal expression ofcolR,colS, orcprSindividually did not. Highly polymyxin-resistantphoQmutants ofP. aeruginosaisolated from polymyxin-treated cystic fibrosis patients harbored mutant alleles ofcolRSandcprS; when expressed in a ΔphoQbackground, these mutant alleles enhanced polymyxin resistance. These results define ColRS and CprRS as two-component systems regulating polymyxin resistance inP. aeruginosa, indicate that addition of 4-amino-l-arabinose to lipid A is not the only PhoPQ-regulated biochemical mechanism required for resistance, and demonstrate thatcolRSandcprSmutations can contribute to high-level clinical resistance.

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