A Copper-responsive Global Repressor Regulates Expression of Diverse Membrane-associated Transporters and Bacterial Drug Resistance in Mycobacteria

Rao, Muding; Liu, Huicong; Yang, Min; Zhao, Chun-Chao; He, Zheng‐Guo

doi:10.1074/jbc.m112.383604

Cited by 20 publications

(15 citation statements)

References 48 publications

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“…It was previously reported that the GntR-like protein NorG is a global regulator of the human pathogen Staphylococcus aureus , which directly or indirectly controls the expression of a wide range of genes, as revealed by transcriptional profiling microarray analysis 26 . The GntR member GfcR was demonstrated to regulate negatively the expression of diverse membrane-associated transporters and bacterial drug resistance in Mycobacterium smegmatis , a fast-growing nonpathogenic mycobacterium 27 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of the GntR family regulator HpaR1 of the crucifer black rot pathogen Xanthomonas campestris pathovar campestris

Liu

et al. 2016

Sci Rep

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The GntR family transcription regulator HpaR1 identified from Xanthomonas campestris pv. campestris has been previously shown to positively regulate the genes responsible for hypersensitive reaction and pathogenicity and to autorepress its own expression. Here, we demonstrated that HpaR1 is a global regulator that positively regulates diverse biological processes, including xanthan polysaccharide production, extracellular enzyme activity, cell motility and tolerance to various stresses. To investigate the regulatory mechanisms of HpaR1, we began with xanthan polysaccharide production, which is governed by a cluster of gum genes. These are directed by the gumB promoter. Disruption of HpaR1 significantly reduced gumB transcription and an electrophoretic mobility shift assay demonstrated that HpaR1 interacts directly with gumB promoter. DNase I footprint analysis revealed that HpaR1 and RNA polymerase were bound to the sequences extending from −21 to +10 and −41 to +29 relative to the transcription initiation site of gumB, respectively. Furthermore, in vitro transcription assays showed that HpaR1 facilitated the binding of RNA polymerase to gumB promoter, leading to an enhancement of its transcription. These results suggest that HpaR1 regulates gumB transcription via a mechanism similar but different to what was found, until now, to only be used by some MerR family transcription activators.

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Section: Discussionmentioning

confidence: 99%

Characterization of the GntR family regulator HpaR1 of the crucifer black rot pathogen Xanthomonas campestris pathovar campestris

Liu

et al. 2016

Sci Rep

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“…Most transcription factors regulate the expression of target genes at the transcriptional level by binding target promoters directly or becoming part of a large transcriptional preinitiation complex (34,35). In the present study, we found that BCG0878c has dual functions, on the one hand, it interacts with promoters of the target gene, whereas on the other, it binds with its cognate protein.…”

Section: Discussionmentioning

confidence: 54%

A TetR Family Transcriptional Factor Directly Regulates the Expression of a 3-Methyladenine DNA Glycosylase and Physically Interacts with the Enzyme to Stimulate Its Base Excision Activity in Mycobacterium bovis BCG

Liu

2014

Journal of Biological Chemistry

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Background:No transcriptional factor has been found to directly regulate expression of the DNA glycosylase in bacteria to date. Results: BCG0878c negatively regulates the expression of MbAAG and stimulates its base excision activity in Mycobacterium bovis BCG. Conclusion: BCG0878c regulates the function of MbAAG both at the transcriptional and post-translational levels. Significance: Our findings reveal a novel mode of regulation of 3MeA DNA glycosylase.

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“…As shown in Fig. 6b , both the Ms0535 (left panel) and Ms0534 deletion strains (right panel) were more sensitive to INH, and their sensitivity could be complemented by inducing the expression of Ms0535 or Ms0534 , respectively, using the pMindD system [ 17 ]. All these strains grew similarly in the absence of INH (Additional file 3 : Figure S3B).…”

Section: Resultsmentioning

confidence: 99%

“…The variable C-terminal domain provides the basis for their classification into six subfamilies. Except for Ms2173, a global Cu 2+ -responsive transcription factor [ 17 ], members of the GntR/FadR subfamily have been rarely reported in M. smegmatis . GntR family members usually function as transcriptional repressors, although some of them are transcriptional activators.…”

Section: Introductionmentioning

confidence: 99%

A GntR family transcription factor positively regulates mycobacterial isoniazid resistance by controlling the expression of a putative permease

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Yang

2015

BMC Microbiol

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BackgroundBacteria use transcriptional regulation to respond to environmental stresses. Specifically, exposure to antibacterial drugs is deemed to be an atypical stress, and altering transcriptional regulation in response to such stress can increase bacterial drug resistance. However, only a few transcription factors that regulate drug resistance have been reported.ResultsIn the present study, a GntR family transcription factor, encoded by the MSMEG_0535 (Ms0535) gene, was shown to be an isoniazid (INH) resistance regulator in Mycobacterium smegmatis. When the Ms0535 gene was overexpressed, cells showed a significant increase in INH resistance. First, the interaction between Ms0535 and its own promoter was determined, and a conserved 26-bp palindromic DNA binding motif was identified using electrophoretic mobility shift and DNaseI footprinting assays. Second, quantitative reverse transcription-PCR assays showed that Ms0535 acted as a transcriptional activator, and positively regulated its own expression, as well as that of a permease encoded by the MSMEG_0534 (Ms0534) gene. Similar to the case for the Ms0535 gene, a recombinant Ms0534-overexpressing strain also exhibited increased INH resistance compared with the wild-type strain. Furthermore, we showed that Ms0535 and Ms0534 deletion strains were more sensitive to INH than the wild-type strain. Interestingly, overexpressing Ms0534 in the Ms0535 deletion strain enhanced its INH resistance. In contrast, the Ms0534 deletion strain was still sensitive to INH even when Ms0535 was overexpressed. These findings suggest that Ms0534 is an effector protein that affects INH resistance in M. smegmatis.ConclusionsIn summary, the GntR transcriptional regulator Ms0535 positively regulates INH resistance by transcriptionally regulating the expression of the Ms0534 permease in M. smegmatis. These results improve our understanding of the role of transcriptional regulation in INH drug resistance in mycobacteria.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0556-8) contains supplementary material, which is available to authorized users.

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A Copper-responsive Global Repressor Regulates Expression of Diverse Membrane-associated Transporters and Bacterial Drug Resistance in Mycobacteria

Cited by 20 publications

References 48 publications

Characterization of the GntR family regulator HpaR1 of the crucifer black rot pathogen Xanthomonas campestris pathovar campestris

Characterization of the GntR family regulator HpaR1 of the crucifer black rot pathogen Xanthomonas campestris pathovar campestris

A TetR Family Transcriptional Factor Directly Regulates the Expression of a 3-Methyladenine DNA Glycosylase and Physically Interacts with the Enzyme to Stimulate Its Base Excision Activity in Mycobacterium bovis BCG

A GntR family transcription factor positively regulates mycobacterial isoniazid resistance by controlling the expression of a putative permease

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