Throughout the course of evolution, bacteria have developed signal transduction tools such as two-component systems (TCSs) to meet their demands to thrive even under the most challenging ...environmental conditions. One TCS called MtrAB is commonly found in
and is implicated in cell wall metabolism, osmoprotection, cell proliferation, antigen secretion, and biosynthesis of secondary metabolites. However, precisely how the MtrAB TCS regulates the bacterial responses to external environments remains unclear. Here, we report that the MtrAB TCS regulates the cell envelope response of alkali-tolerant bacterium
sp. strain DQ12-45-1b to extreme alkaline stimuli. We found that under alkaline conditions, an
mutant exhibited both reduced growth and abnormal morphology compared to the wild-type strain. Electrophoretic mobility shift assay analysis showed that MtrA binds the promoter of the
gene critical for cell wall homeostasis, suggesting that MtrA directly controls transcription of this regulator. In conclusion, our findings demonstrate that MtrAB TCS is involved in controlling the bacterial response to alkaline stimuli by regulating the expression of the cell wall homeostasis regulator MraZ in
sp. DQ12-45-1b, providing novel details critical for a mechanistic understanding of how cell wall homeostasis is controlled.
Microorganisms can be found in most extreme environments, and they have to adapt to a wide range of environmental stresses. The two-component systems (TCSs) found in bacteria detect environmental stimuli and regulate physiological pathways for survival. The MtrAB TCS conserved in
is critical for maintaining the metabolism of the cell wall components that protects bacteria from diverse environmental stresses. However, how the MtrAB TCS regulates cell wall homeostasis and adaptation under stress conditions is unclear. Here, we report that the MtrAB TCS in
sp. DQ12-45-1b plays a critical role in alkaline resistance by modulating the cell wall homeostasis through the MtrAB-MraZ pathway. Thus, our work provides a novel regulatory pathway used by bacteria for adaptation and survival under extreme alkaline stresses.
The mraZ and mraW genes are highly conserved in bacteria, both in sequence and in their position at the head of the division and cell wall (dcw) gene cluster. Located directly upstream of the mraZ ...gene, the Pmra promoter drives the transcription of mraZ and mraW, as well as many essential cell division and cell wall genes, but no regulator of Pmra has been found to date. Although MraZ has structural similarity to the AbrB transition state regulator and the MazE antitoxin and MraW is known to methylate the 16S rRNA, mraZ and mraW null mutants have no detectable phenotypes. Here we show that overproduction of Escherichia coli MraZ inhibited cell division and was lethal in rich medium at high induction levels and in minimal medium at low induction levels. Co-overproduction of MraW suppressed MraZ toxicity, and loss of MraW enhanced MraZ toxicity, suggesting that MraZ and MraW have antagonistic functions. MraZ-green fluorescent protein localized to the nucleoid, suggesting that it binds DNA. Consistent with this idea, purified MraZ directly bound a region of DNA containing three direct repeats between Pmra and the mraZ gene. Excess MraZ reduced the expression of an mraZ-lacZ reporter, suggesting that MraZ acts as a repressor of Pmra, whereas a DNA-binding mutant form of MraZ failed to repress expression. Transcriptome sequencing (RNA-seq) analysis suggested that MraZ also regulates the expression of genes outside the dcw cluster. In support of this, purified MraZ could directly bind to a putative operator site upstream of mioC, one of the repressed genes identified by RNA-seq.
In recent years, multidrug-resistant methicillin-resistant
has become increasingly prevalent, which raised a huge challenge to antibiotic treatment of infectious diseases. The anti-virulence strategy ...targeting virulent factors is a promising novel therapy for
infection. The virulence mechanism of
was needed to explore deeply to develop more targets and improve the effectiveness of anti-virulence strategies.
In this study, we found
was highly conserved in
, and its production is homologous with the MraZ of
, a transcriptional regulator involved in the growth and cell division of
. To investigate the function of
in
, we constructed a MW2
deletion mutant and its complementary mutant for virulence comparison. Although no remarkable influence on the growth, the
deletion mutant led to significantly reduced resistance to human neutrophils and decreased virulence in
model as well as mouse skin and soft tissue infection models, indicating its essential contribution to virulence and immune evasion to support the pathogenicity of
infection. RNA-Seq and quantitative RT-qPCR revealed that MraZ is a multi-functional regulator; it involves in diverse biological processes and can up-regulate the expression of various virulence genes by
and
.
plays vital roles in the pathyogenicity of
via regulating many virulence genes. It may be an attractive target for anti-virulence therapy of
.
As the area of visual studies grows within the field of Latin American Studies, one area of especially rapid expansion is Latin America photography. In this interview (July 1, 2015; Mexico City) John ...Mraz, a pioneer in the study of Mexican photography, not only shares the story of how he came to undertake the study of visual history, but also reveals important lessons he has learned over the course of his study and career.
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