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Toxins 2018, 10(11), 424; https://doi.org/10.3390/toxins10110424

HigB Reciprocally Controls Biofilm Formation and the Expression of Type III Secretion System Genes through Influencing the Intracellular c-di-GMP Level in Pseudomonas aeruginosa

1
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
2
Meishan Product Quality Supervision and Inspection Institute and National Pickle Quality Inspection Center, Meishan 620000, China
3
Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
*
Author to whom correspondence should be addressed.
Received: 20 September 2018 / Revised: 21 October 2018 / Accepted: 22 October 2018 / Published: 24 October 2018
(This article belongs to the Special Issue Toxin-antitoxin (TA) systems)
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Abstract

Toxin-antitoxin (TA) systems play important roles in bacteria persister formation. Increasing evidence demonstrate the roles of TA systems in regulating virulence factors in pathogenic bacteria. The toxin HigB in Pseudomonas aeruginosa contributes to persister formation and regulates the expression of multiple virulence factors and biofilm formation. However, the regulatory mechanism remains elusive. In this study, we explored the HigB mediated regulatory pathways. We demonstrate that HigB decreases the intracellular level of c-di-GMP, which is responsible for the increased expression of the type III secretion system (T3SS) genes and repression of biofilm formation. By analyzing the expression levels of the known c-di-GMP metabolism genes, we find that three c-di-GMP hydrolysis genes are up regulated by HigB, namely PA2133, PA2200 and PA3825. Deletion of the three genes individually or simultaneously diminishes the HigB mediated regulation on the expression of T3SS genes and biofilm formation. Therefore, our results reveal novel functions of HigB in P. aeruginosa. View Full-Text
Keywords: toxin-antitoxin system; HigB/HigA; Pseudomonas aeruginosa; type III secretion system; biofilm; c-di-GMP toxin-antitoxin system; HigB/HigA; Pseudomonas aeruginosa; type III secretion system; biofilm; c-di-GMP
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Zhang, Y.; Xia, B.; Li, M.; Shi, J.; Long, Y.; Jin, Y.; Bai, F.; Cheng, Z.; Jin, S.; Wu, W. HigB Reciprocally Controls Biofilm Formation and the Expression of Type III Secretion System Genes through Influencing the Intracellular c-di-GMP Level in Pseudomonas aeruginosa. Toxins 2018, 10, 424.

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