Survival strategies in bacterial populations during persistent lung infections
Patients suffering from the genetic disorder cystic fibrosis (CF) are nearly always infected with various microorganisms in their airways. Investigations of the very common infecting pathogen in CF – Pseudomonas aeruginosa – have shown that these infections develop over relatively short time periods into persistent and eventually chronic infections despite a functional immune system and continuous treatment with several antibiotics. Only very limited high-level antibiotic resistance, however, appears among clinical isolates of these bacteria during the first decade of infection, and it is therefore important to identify alternative mechanisms employed by P. aeruginosa to persist in presence of antibiotics. Moreover, in cases of actual high-level resistance development in the bacteria derived from the CF patients, we frequently observe that the underlying mutations are different from those, which usually are considered to be the most common based on laboratory selection experiments. Such observations are important to consider in connection with attempts to develop bioinformatics based tools for prediction and diagnosis of antibiotic resistance.
I will briefly summarize our knowledge about persistence mechanisms unrelated to high-level antibiotic resistance derived from investigations of CF clinical isolates of P. aeruginosa. I will further describe in some detail a case of high-level resistance to aminoglycosides associated with collateral sensitivity to chloramphenicol. The associated mutation in a gene for a ribosomal protein is very distinct from usually reported aminoglycoside resistance mutations. High-resolution structural analysis of the ribosomes from this mutant strain offers explanations of most/all of the phenotypes connected with the mutation in the r-protein gene.
Host: Paul Rainey
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