Impact of QseBC system in c-di-GMP-dependent quorum sensing regulatory network in a clinical isolate SSU of Aeromonas hydrophila

Elena V. Kozlova, Bijay K. Khajanchi, Vsevolod L. Popov, Julie Wen, Ashok K. Chopra

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Our earlier studies showed that AhyRI- (AI-1) and LuxS-based (AI-2) quorum sensing (QS) systems were positive and negative regulators of virulence, respectively, in a diarrheal isolate SSU of Aeromonas hydrophila. Recently, we demonstrated that deletion of the QseBC two-component signal transduction system (AI-3 QS in enterohemorrhagic Escherichia coli) also led to an attenuation of A. hydrophila in a septicemic mouse model of infection, and that interplay exists between AI-1, AI-2, and the second-messenger cyclic-di-guanosine monophosphate (c-di-GMP) in modulating bacterial virulence. To further explore a network connection between all of the three QS systems in A. hydrophila SSU and their cross talk with c-di-GMP, we overproduced a protein with a GGDEF domain, which increases c-di-GMP levels in bacteria, and studied phenotypes and transcriptional profiling of genes involved in biofilm formation and motility of the wild-type (WT) A. hydrophila and its Δ. qseB mutant. Over-expression of the GGDEF domain-encoding gene (aha0701h) resulted in a significantly reduced motility of the WT A. hydrophila similar to that of the Δ. qseB mutant. While enhanced protease production was noted in WT A. hydrophila that had increased c-di-GMP, no enzymatic activity was detected in the Δ. qseB mutant overexpressing the aha0701h gene. Likewise, denser biofilm formation was noted for WT bacteria when c-di-GMP was overproduced compared to its respective control; however, overproduction of c-di-GMP in the Δ. qseB mutant led to reduced biofilm formation, a finding similar to that noted for the parental A. hydrophila strain. These effects on bacterial motility and biofilm formation in the Δ. qseB mutant or the mutant with increased c-di-GMP were correlated with altered levels of fleN and vpsT genes. While we noted transcript levels of qseB and qseC genes to be increased in the ahyRI mutant, down-regulation of the ahyR and ahyI genes was observed in the Δ. qseB mutant, which correlated with decreased protease activity. Finally, an enhanced virulence of WT A. hydrophila with increased c-di-GMP was noted in a mouse model when compared to findings in the parental strain with vector alone. Overall, we conclude that cross talk between AI-1 and QseBC systems exists in A. hydrophila SSU, and c-di-GMP modulation on QseBC system is dependent on the expression of the AI-1 system.

Original languageEnglish (US)
Pages (from-to)115-124
Number of pages10
JournalMicrobial Pathogenesis
Volume53
Issue number3-4
DOIs
StatePublished - Sep 1 2012

Keywords

  • 2-Component QseBC system
  • Aeromonas hydrophila
  • Biofilm formation
  • C-di-GMP
  • Gene transcription
  • Motility
  • Mouse model of infection
  • Quorum sensing systems

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

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