Resistance versus Virulence

The conventional wisdom is that bacteria pay a “fitness cost” as they accumulate antibiotic resistances, a phenomenon I discussed in a short post last year. More resistant, but less fit, and (one hopes) less virulent. Thus some of the most problematic multi-drug resistant organisms (MDROs), such as Acinetobacter, cause disease almost exclusively in the most vulnerable patients—those bugs simply aren’t virulent enough to wreak their havoc in the healthy. When an MDRO does emerge as a major community scourge, as was the case with community-associated MRSA, it’s big news.

So I was surprised (not pleasantly) to read this report in PNAS about Pseudomonas aeruginosa strains that refused to adhere to convention. Using a mouse model and well-characterized P. aeruginosa mutants, the investigators found that strains with mutations in a gene encoding a particular outer membrane protein (one that provides an entry channel for carbapenem antibiotics) were more virulent—more likely to disseminate from the mouse GI tract, and more resistant to in vitro killing by acidic conditions or human serum. Now mice are not men, and a murine gut colonization model isn’t necessarily predictive of an organism’s ability to cause infection at various human body sites. Still, it is nerve-wracking to know that our carbapenem use might produce P. aeruginosa strains that are not only more resistant, but also more virulent! As the title of the accompanying editorial points out, it is indeed a “worst case scenario”.

Scanning EM of P. aeruginosa from the Public Health Image Library