Abstract
Cystic fibrosis (CF) is the most common life-threatening genetic disease among Caucasians. CF patients suffer from chronic lung infections due to the presence of thick mucus, caused by cftr gene dysfunction. The two most commonly found bacteria in the mucus of CF patients are Staphylococcus aureus and Pseudomonas aeruginosa. It is well known that early-infecting P. aeruginosa strains produce anti-staphylococcal compounds and inhibit S. aureus growth. More recently, it has been shown that late-infecting P. aeruginosa strains develop commensal-like/coexistence interaction with S. aureus. The aim of this study was to decipher the impact of P. aeruginosa strains on S. aureus. RNA sequencing analysis showed 77 genes were specifically dysregulated in the context of competition and 140 genes in the context of coexistence in the presence of P. aeruginosa. In coexistence, genes encoding virulence factors and proteins involved in carbohydrates, lipids, nucleotides and amino acids metabolism were downregulated. On the contrary, several transporter family encoding genes were upregulated. In particular, several antibiotic pumps belonging to the Nor family were upregulated: tet38, norA and norC, leading to an increase in antibiotic resistance of S. aureus when exposed to tetracycline and ciprofloxacin and an enhanced internalization rate within epithelial pulmonary cells. This study shows that coexistence with P. aeruginosa affects the S. aureus transcriptome and virulence.
Highlights
Cystic fibrosis (CF) is the most common life-threatening genetic disease among Caucasians
Coexistence interaction involves more than half of the S. aureus and P. aeruginosa isolates from co-infected CF patients
Two types of interactions between S. aureus and P. aeruginosa could be observed with CF patient isolates: the well-described competitive phenotype, where P. aeruginosa inhibits S. aureus growth[16], and the newly described phenotype of coexistence, where P. aeruginosa is unable to outcompete S. aureus[19,20,21]
Summary
Cystic fibrosis (CF) is the most common life-threatening genetic disease among Caucasians. The two most commonly found bacteria in the mucus of CF patients are Staphylococcus aureus and Pseudomonas aeruginosa. It has been shown that late-infecting P. aeruginosa strains develop commensal-like/coexistence interaction with S. aureus. One of the most well-known examples of pathologies in which many bacterial interactions are described are lung diseases occurring during Cystic Fibrosis (CF). Infections by P. aeruginosa occur later with the highest prevalence in adults (70% among 35–44 year-old patients). These bacteria seem to succeed one another, they are not mutually exclusive since patients are frequently diagnosed as being co-infected by S. aureus and P. aeruginosa (from 35% to 50%)[6,7]. Different mechanisms have been described[16]: for example, P. aeruginosa secreted products can inhibit the growth or lyse S. aureus as well as induce epithelial cells to kill S. aureus and other Gram-positive bacteria[8,17,18]
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