Date Published: June 30, 2017
Publisher: Public Library of Science
Author(s): Silvia Ferrara, Marilena Falcone, Raffaella Macchi, Alessandra Bragonzi, Daniela Girelli, Lisa Cariani, Cristina Cigana, Giovanni Bertoni, Eric Cascales.
Small non-coding RNAs (sRNAs) are post-transcriptional regulators of gene expression that have been recognized as key contributors to bacterial virulence and pathogenic mechanisms. In this study, we characterized the sRNA PesA of the opportunistic human pathogen Pseudomonas aeruginosa. We show that PesA, which is transcribed within the pathogenicity island PAPI-1 of P. aeruginosa strain PA14, contributes to P. aeruginosa PA14 virulence. In fact, pesA gene deletion resulted in a less pathogenic strain, showing higher survival of cystic fibrosis human bronchial epithelial cells after infection. Moreover, we show that PesA influences positively the expression of pyocin S3 whose genetic locus comprises two structural genes, pyoS3A and pyoS3I, encoding the killing S3A and the immunity S3I proteins, respectively. Interestingly, the deletion of pesA gene results in increased sensitivity to UV irradiation and to the fluoroquinolone antibiotic ciprofloxacin. The degree of UV sensitivity displayed by the PA14 strain lacking PesA is comparable to that of a strain deleted for pyoS3A-I. These results suggest an involvement of pyocin S3 in DNA damage repair and a regulatory role of PesA on this function.
Bacterial small RNAs (sRNAs) have been recognized as key contributors to regulatory networks, and have been shown to play critical roles in many intra- and extracellular processes, and in pathogenesis [1–3]. Most sRNAs exert their regulatory function post-transcriptionally, acting by base pairing with the mRNA of their target genes ultimately modulating mRNA translation and/or stability. sRNAs can share extended base complementarity when they are cis-encoded on the opposite strand of the target mRNA, or they can interact with the target mRNA via short and imperfect base pairing, as in the case of trans-encoded sRNAs. The expression of most sRNAs is responsive to environmental stress conditions spanning from iron and oxygen limitation, to oxidative, metabolic/nutrient, pH and cell envelope stresses .
We studied the novel P. aeruginosa sRNA PesA, which was originally identified as being transcribed from the horizontally acquired pathogenicity island PAPI-1 in the strain PA14. Our analysis revealed that PesA is widespread in clinical isolates from patients affected by chronic respiratory diseases, such as CF, being expressed in 55% of the cases tested. Moreover, PesA expression is responsive to low oxygen conditions, a hallmark of CF and COPD, and impacts P. aeruginosa pathogenicity in CF bronchial cells. These results suggest that PesA could be relevant during P. aeruginosa infection in chronic respiratory diseases.