β-Lactamase diversity in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a clinically important Gram-negative pathogen responsible for a wide variety of serious nosocomial and community-acquired infections. Antibiotic resistance is a major concern, as this organism has a wide variety of resistance mechanisms, including chromosomal class C (bla_PDC) and D (bla_OXA-50 family) β-lactamases, efflux pumps, porin channels, and the ability to readily acquire additional β-lactamases. Surveillance studies can reveal the diversity and distribution of β-lactamase alleles but are difficult and expensive to conduct. Herein, we apply a novel approach, using publicly available data derived from whole genome sequences, to explore the diversity and distribution of β-lactamase alleles across 30,452 P. aeruginosa isolates. The most common alleles were bla_PDC-3, bla_PDC-5, bla_PDC-8, bla_OXA-488, bla_OXA-50, and bla_OXA-486. Interestingly, only 43.6% of assigned bla_PDC alleles were encountered, and the 10 most common bla_PDC and intrinsic bla_OXA alleles represent approximately 75% of their respective total alleles, while many other assigned alleles were extremely uncommon. As anticipated, differences were observed over time and geography. Surprisingly, more distinct unassigned alleles were encountered than distinct assigned alleles. Understanding the diversity and distribution of β-lactamase alleles helps to prioritize variants for further research, select targets for drug development, and may aid in selecting therapies for a given infection.