OVK, PDM, RCD, and DS aided in sample processing for proteomic analysis. PE and OVK performed MS runs. VS performed statistical analysis on MS data. All authors read and approved the final manuscript.”
“Background Pseudomonas aeruginosa is a versatile Gram-negative bacterium, able to metabolise multiple carbon sources and exploit diverse ecological niches, e.g. soil, water, plants and animal hosts [1, 2]. This opportunistic pathogen causes a range of human infections, including acute infections
of severe wounds [3] and burns [4, 5] and chronic lung infections in cystic fibrosis (CF) patients [6]. P. aeruginosa forms biofilms in the CF lung that are highly resistant to antibiotics and clearance by the immune system [7]. Once established, such biofilms cannot be eradicated and are learn more associated with greatly increased morbidity and mortality [8]. Several CF-associated transmissible E7080 nmr strains of P. aeruginosa, capable of between patient transmission, have been identified in the UK, Europe, Australia and North America [9]. The Liverpool Epidemic Strain (LES), a UK transmissible strain, was first isolated in 1996 at Alder Hey Children’s Hospital (AHCH), Liverpool [10]. This strain is capable of super-infection, supplanting pre-existing P. aeruginosa populations in the CF lung [11]. Chronic infection with LES is associated with increased morbidity and
mortality compared to other P. aeruginosa strains [12]. The LES is highly prevalent within individual hospital CF units [13] and is the most abundant see more P. aeruginosa strain amongst CF patients in the UK [14]. It was also recently isolated from the sputa of CF patients in North America [15]. Sequencing of the earliest LES isolate, LESB58, demonstrated that the genome shares 95% similarity
with the lab strain PAO1. However, its core genome is punctuated by multiple norfloxacin-inducible prophages [16]. Specifically, there are five inducible prophage genomes (LESφ2; LESφ3 LESφ4 LESφ5 and LESφ6) that are mosaic in nature. The gene organisation of LESφ2 and LESφ3 resembles that of lambdoid phages. These two phage genomes share 82.2% Ketotifen identity across a 13.6-kb region at their 3’ ends that makes up 32% of the phage genomes. The closest known relative to both these phages is the Pseudomonas phage F10 [17]. LESφ3 also contains a 7.5 kb region that shares 99.8% homology with LESφ5, which exhibits a considerable sequence similarity to the O-antigen converting phage D3 [18]. LESφ4 is a transposable Mu-like phage that closely resembles phage D3112 [19]. The LESφ6 sequence resembles a pf1-like filamentous phage [16]. Temperate phages have been shown to confer selective, beneficial traits to a range of P. aeruginosa hosts [20]. For example, phage D3 orchestrates O antigen conversion from O5 to O16 in PAO1, which may aid evasion of the immune system and resistance to phage superinfection [18, 21].
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