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Nucleic Acids Res. 2014;42(16):10307-20. doi: 10.1093/nar/gku586. Epub 2014 Jul 17.

Molecular mechanisms of master regulator VqsM mediating quorum-sensing and antibiotic resistance in Pseudomonas aeruginosa.

Author information

1
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi 710069, China Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA lianghh@nwu.edu.cn.
2
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
3
Department of Basic Science, School of Medicine and Health Science, University of North Dakota, 501 North Columbia Rd, EJRF Building, Room 2726, ND 58203, USA.

Abstract

The Pseudomonas aeruginosa quorum-sensing (QS) systems contribute to bacterial homeostasis and pathogenicity. Although the AraC-family transcription factor VqsM has been characterized to control the production of virulence factors and QS signaling molecules, its detailed regulatory mechanisms still remain elusive. Here, we report that VqsM directly binds to the lasI promoter region, and thus regulates its expression. To identify additional targets of VqsM in P. aeruginosa PAO1, we performed chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) and detected 48 enriched loci harboring VqsM-binding peaks in the P. aeruginosa genome. The direct regulation of these genes by VqsM has been confirmed by electrophoretic mobility shift assays and quantitative real-time polymerase chain reactions. A VqsM-binding motif was identified by using the MEME suite and verified by footprint assays in vitro. In addition, VqsM directly bound to the promoter regions of the antibiotic resistance regulator NfxB and the master type III secretion system (T3SS) regulator ExsA. Notably, the vqsM mutant displayed more resistance to two types of antibiotics and promoted bacterial survival in a mouse model, compared to wild-type PAO1. Collectively, this work provides new cues to better understand the detailed regulatory networks of QS systems, T3SS, and antibiotic resistance.

PMID:
25034696
PMCID:
PMC4176358
DOI:
10.1093/nar/gku586
[Indexed for MEDLINE]
Free PMC Article

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