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Environ Microbiol. 2019 Mar 18. doi: 10.1111/1462-2920.14595. [Epub ahead of print]

Antitoxin HigA Inhibits Virulence Gene mvfR Expression in Pseudomonas aeruginosa.

Guo Y1, Sun C1,2,3, Li Y1,2, Tang K1, Ni S1, Wang X1,2.

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Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.
Basic Medical School of Guizhou University of Traditional Chinese Medicine, Guiyang, China.


Toxin/antitoxin (TA) systems are ubiquitous in bacteria and archaea, and participate in biofilm formation and stress responses. The higBA locus of the opportunistic pathogen Pseudomonas aeruginosa encodes a type II TA system. Previous work found that the higBA operon is cotranscribed and that HigB toxin regulates biofilm formation and virulence expression. In this study, we demonstrate that HigA antitoxin is produced at a higher level than HigB and that higA mRNA is expressed separately from a promoter inside higB during the late stationary phase. Critically, HigA represses the expression of mvfR, which is an important virulence-related regulator, by binding to a conserved HigA palindrome (5'-TTAAC GTTAA-3') in the mvfR promoter, and the binding of HigB to HigA derepresses this process. During the late stationary phase, excess HigA represses the expression of mvfR and higBA. However, in the presence of aminoglycoside antibiotics where Lon protease is activated, the degradation of HigA by Lon increases P. aeruginosa virulence by simultaneously derepressing mvfR and higB transcription. Therefore, this study reveals that the antitoxin of the P. aeruginosa TA system is integrated into the key virulence regulatory network of the host and functions as a transcriptional repressor to control the production of virulence factors. This article is protected by copyright. All rights reserved.


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