3%) and c3719 (1.2%) have significantly smaller proportions compared to total CDS than does AES-1R (p<0.0001 for both comparisons). The proportion of unique CDS in AES-1R selleck chemicals llc is similar to that for Pa2192 (p=0.83). The 338 unique CDS (Table S1) are heavily concentrated between AES_6966 and AES_7152, thus there is a high likelihood that this 187-CDS region represents a portion of the AES-1R accessory genome. AES-1R contains at least one novel integrated prophage in this region, with 16 CDS having a known or putative phage function. Amongst these are two Mu-like prophage proteins (gp28 and gp29). Mu-like proteins have been identified in a number of pathogenic bacteria including Haemophilus ducreyi, Shigella sonnei, Escherichia coli 0157:H7, Bordetella bronchiseptica and the Pseudomonas-related species Burkholderia cenocepacia [28].

Prophages have been identified in LES [29] and c3719 genomes [30], however BLAST searches of genes from the AES-1R prophage failed to identify homologs in these epidemic strains. There was no discernable pattern of differential expression by genes in this putative accessory region in the AES-1R/1M array comparison conducted in this study. However the upregulation of two non-PAO1 genes belonging to PAGI-5 is interesting as it links AES-1R to the pathogenic features of this gene island found in PA7 and PACS2. PAGI-5-containing strains have been shown to be more virulent than non-PAGI-5 strains in mammalian models [31]. A major objective of this study was to utilize the AES-1R sequence and the PANarray to elucidate the differences and similarities in gene expression between the acute and chronic isolates of AES-1.

The finding that certain virulence-related genes were upregulated in chronic infection isolate AES-1M has relevance in areas including biofilm development, transmissibility, antibiotic resistance, pyomelanin-related persistence and lung surfactant secretion (Table 2). The upregulation of adhA is required for P. aeruginosa biofilm development [32] and biofilms are important in virulence and persistence. We previously reported that AES-1 strains produce significantly larger biofilms than non-epidemic strains [33] thus the upregulated expression of biofilm-related genes in AES-1M would enhance its ability to persist.

T3SS genes are generally switched off or downregulated at chronic infection and several including pcrV, pscC and pscI were significantly downregulated in AES-1M; however pscD, a regulatory T3SS gene [34] was significantly upregulated in AES-1M. As a functioning regulator, pscD may trigger the T3SS and enable AES-1M to infect other CF patients from the environment or transmit to other patients via aerosols from an infected patient. ppiA is one of four periplasmic isomerases in E. coli, inactivation of which leads to a decreased growth rate and increased susceptibility to certain antibiotics [35]. It has Carfilzomib been shown in E.