Mapping Antibiotic Resistance Determinants in Oral Streptococci

Abstract

Antibiotic resistance is a global priority in health care. Leveraging thousands of whole-genome sequences, here we reveal the core resistance determinants of oral streptococci, focusing on assessing pattern variability and gene exchange across commensals and pathogens. Genomic information was obtained from the National Center for Biotechnology Information. Determinants of antibiotic resistance were identified using AMRFinderPlus and the Comprehensive Antibiotic Resistance Database. ICEscreen was employed for calling of integrative and conjugative elements. Variability and recombination in penicillin-binding protein sequences were assessed with MMseqs2 and fastGEAR. A total of 2,087 genomes from 15 species were included, representing the mitis, mutans, anginosus, salivarius, and bovis groups. We observed 3,576 hits from 55 unique resistance genes conferring resistance to 11 antibiotic classes. The species with the most resistance determinants per genome against unique antibiotic classes were Streptococcus mitis (2.7), Streptococcus oralis (2.5), Streptococcus parasanguinis (1.9), Streptococcus gallolyticus (1.3), and Streptococcus anginosus (1.2). The 2 latter species also presented the most diverse composition of determinants. Over 1,800 integrative and conjugative elements were predicted across all genomes, with nearly 17% carrying at least 1 antibiotic resistance gene. Penicillin-binding protein variation analyses showed a high diversity in the mitis group. Even though S. mitis and S. oralis composed less than 4% of the genomes included in the analyses, they were recognized as sources of DNA for over a third of recombination events in pbp1a and nearly half for both pbp2b and pbp2x in β-lactam-resistant isolates of Streptococcus pneumoniae . In summary, we show that tetracycline and macrolide resistance were highly abundant and tightly connected to integrative and conjugative elements. Further, recent recombination data in pbp loci show frequent genetic exchange from oral streptococci to β-lactam-resistant S. pneumoniae . Fundamentally, assessing triggers and the dynamics of genetic exchange across species is central to the development of strategies aiming to mitigate the impact of antibiotic resistance.