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J Bacteriol. 2019 Aug 12. pii: JB.00362-19. doi: 10.1128/JB.00362-19. [Epub ahead of print]

Differential modulation of Quorum-Sensing signaling through QslA in Pseudomonas aeruginosa strains PAO1 and PA14.

Author information

1
LISM (Laboratoire d'Ingénierie des Systèmes Macromoléculaires-UMR7255), IMM (Institut de Microbiologie de la Méditerranée), Aix-Marseille Univ and CNRS, 31 chemin J. Aiguier, Marseille 13402 Cedex 20, France. thibault.sana@epfl.ch bleves@imm.cnrs.fr.
2
Genomics of Gene Expression Laboratory Centro de Investigación Príncipe Felipe, Valencia, Spain.
3
LISM (Laboratoire d'Ingénierie des Systèmes Macromoléculaires-UMR7255), IMM (Institut de Microbiologie de la Méditerranée), Aix-Marseille Univ and CNRS, 31 chemin J. Aiguier, Marseille 13402 Cedex 20, France.
4
Microbiology and Cell Science, IFAS, Genetics Insitutte, University of Florida, Gainesville, FL, United States.

Abstract

Two clinical isolates of the opportunist pathogen Pseudomonas aeruginosa named PAO1 and PA14 are commonly studied in research laboratories. Despite being closely related, PA14 exhibits increased virulence compared to PAO1 in various models. To determine which players are responsible for the hypervirulence phenotype of the PA14 strain, we elected for a transcriptomic approach through RNA sequencing. We found 2029 genes that are differentially expressed between the two strains, including several genes that are involved with or regulated by Quorum-Sensing (QS), known to control most of the virulence factors in P. aeruginosa Among them, we chose to focus our study on QslA, an anti-activator of QS whose expression was barely detectable in the PA14 strain according our data. We hypothesized that lack of expression of qslA in PA14 could be responsible for higher QS expression in the PA14 strain, possibly explaining its hyper-virulence phenotype. After confirming QslA protein was highly produced in PAO1 but not in the PA14 strain, we provided evidence showing that a PAO1 deletion strain of qslA has faster QS gene expression kinetics compared to PA14. Moreover, known virulence factors activated by QS such as (i) pyocyanin production, (ii) H2-T6SS (Type VI Secretion System) gene expression, and (iii) Xcp-T2SS (Type II Secretion System) machinery production and secretion were all lower in PAO1 compared to PA14 strain, due to higher qslA expression. However, biofilm formation and cytotoxicity towards macrophages, although increased in PA14 compared to PAO1, were independent of QslA control. Altogether, our findings implicated differential qslA expression as a major determinant of virulence factor expression in P. aeruginosa strains PAO1 and PA14.Importance Pseudomonas aeruginosa is an opportunistic pathogen responsible for acute nosocomial infections, and chronic pulmonary infections. P. aeruginosa strain PA14 is known to be hyper-virulent in different hosts. Despite several studies in the field, the underlining molecular mechanisms sustaining this phenotype remain enigmatic. Here, we provide evidence that the PA14 strain has faster Quorum-Sensing (QS) kinetics compared to the PAO1 strain, due to the lack of QslA expression, an anti-activator of QS. QS is a major regulator of virulence factors in P. aeruginosa, therefore we propose that the hyper-virulent phenotype of PA14 strain is, at least partially, due to the lack of QslA expression. This mechanism could be of great importance, as it could be conserved amongst other P. aeruginosa isolates.

PMID:
31405911
DOI:
10.1128/JB.00362-19

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