Abstract
Pseudomonas aeruginosa, a human opportunistic pathogen, is capable of provoking acute and chronic infections that are associated with defined sets of virulence factors. During chronic infections, the bacterium accumulates mutations that silence some and activate other genes. Here we show that the cystic fibrosis isolate CHA exhibits a unique virulence phenotype featuring a mucoid morphology, an active Type III Secretion System (T3SS, hallmark of acute infections), and no Type VI Secretion System (H1-T6SS). This virulence profile is due to a 426 bp deletion in the 3′ end of the gacS gene encoding an essential regulatory protein. The absence of GacS disturbs the Gac/Rsm pathway leading to depletion of the small regulatory RNAs RsmY/RsmZ and, in consequence, to expression of T3SS, while switching off the expression of H1-T6SS and Pel polysaccharides. The CHA isolate also exhibits full ability to swim and twitch, due to active flagellum and Type IVa pili. Thus, unlike the classical scheme of balance between virulence factors, clinical strains may adapt to a local niche by expressing both alginate exopolysaccharide, a hallmark of membrane stress that protects from antibiotic action, host defences and phagocytosis, and efficient T3S machinery that is considered as an aggressive virulence factor.
Highlights
Pseudomonas aeruginosa is an opportunistic Gram negative bacterium able to trigger either severe acute or chronic human infections, depending on the environmental signals it encounters
As cystic fibrosis (CF) strains usually exhibit a decreased toxicity compared to strains triggering acute infection [9], we compared the virulence of CHA in mice to that of the PAO1 reference strain, which is a wound isolate
The CHA strain was clearly more virulent than the PAO1 strain in a murine acute model of lung infection (Figure S1A); this was associated with an increased dissemination of the bacteria both in blood and spleen compared to PAO1 (Figure S1B)
Summary
Pseudomonas aeruginosa is an opportunistic Gram negative bacterium able to trigger either severe acute or chronic human infections, depending on the environmental signals it encounters. P. aeruginosa has to survive and adapt to the stressful environment encountered in the CF lungs where it is continuously exposed to antibiotics, oxidative and osmotic stresses as well as active host immune system. The CF respiratory mucus has been shown to directly impact bacterial gene transcription [2,3]. A CF mucoid strain was reported to trigger, in response to the CF niche, the synthesis of enzymes protecting the bacteria against oxidative stress and the activation of genes encoding the HSI-I Type VI Secretion System (H1T6SS), known to play a role in bacterial competition [4,5,6]. The alginate production was unexpectedly repressed, and the expression of two small RNAs (PA2G_05393.1 and PA2G_03487.1) with putative regulatory roles was observed, pointing out the major effect of contact with CF mucus on bacterial physiology [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
