Genomic characterization of group B Streptococcus from Argentina: insights into prophage diversity, virulence factors and antibiotic resistance genes

Abstract

Group B Streptococcus (GBS) is a commensal bacterium that can cause severe infections in infants and adults with comorbidities. Resistance and reduced susceptibility to antibiotics is continually on the rise, and vaccines remain in-development. Prophages have been reported to contribute to GBS evolution and pathogenicity. However, no studies are available to date on prophage contribution to the epidemiology of GBS isolates from humans in South America. In the context of an Argentinian multicentric study, we had previously phenotypically characterised 365 human GBS isolates from invasive disease, urinary infections and maternal colonisation. These isolates had been whole genome sequenced and their prophage presence bioinformatically determined. In this study, we genomically characterised the isolates and analysed the prophage content in the context of the epidemiological data. The phylogenetic analysis of the 365 genomes with 103 GBS from public databases revealed that Argentinian GBS were related to isolates from around the world. The most prevalent lineages, independently of the isolate source, were CC23/Ia and CC12/Ib. Genes encoding virulence factors involved in immune response evasion, tissue damage and adherence to host tissues and invasion were found in all of the genomes in accordance with previously described lineage distribution. According to the prevalent capsular types and the distribution of specific virulence factors in Argentinian GBS, over 95% coverage would be expected from the vaccines currently under development. Antibiotic resistance determinants (ARDs) to at least one antibiotic class were found in 90% of the genomes, including novel mutations in pbp2x, while more than 15% carried ARDs to 3 or more classes. GBS collected from urinary infections carried a significantly higher proportion of ARDs to multiple antibiotic classes than the rest of the isolates. A total of 454 prophages were found among the 468 genomes analysed, which were classified into 23 prophage types. Prophage presence exhibited variations based on GBS clonal complex and capsular type. A possible association between an increased GBS pathogenicity and the carriage of prophages with integrase type GBSInt8 and/or the presence of genes that encode the Phox Homology domain has been observed. The highest prevalence of prophages per genome was found in lineages CC17/III and CC19/III, while the lowest amount was observed in CC12/Ib. Overall, the highest density of prophages, virulence factors and ARDs determinants was found in CC19 isolates, mostly of capsular type III, independently of the isolates source. This is the first analysis of the human-associated GBS population in South America based on whole genome sequencing data, which will make a significant contribution to future studies on the global GBS population structure