Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Abstract

International audienceStreptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of ​tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates

Sequence type 1 group B Streptococcus , an emerging cause of invasive disease in adults, evolves by small genetic changes

“…Macrolide resistance factors were present at a relatively higher rate in the present study (59%; SI Appendix, Fig. S5A) than what has been reported in other GBS studies (10,17). The majority of macrolide resistance elements were ermB or ermTR (SI Appendix, Fig.…”

“…When present, tetM was invariably located in the transposable element Tn916 inserted in RDF.2 (SI Appendix, Fig. S1) at the location reported for the Tn916-1 lineage by Da Cunha et al (10). Macrolide resistance factors were present at a relatively higher rate in the present study (59%; SI Appendix, Fig.…”

“…S3D). We additionally analyzed 24 serotype V ST-1 strains from three different continents and for which whole-genome data were recently reported (10) and found that the strains were interspersed among our North American isolates, suggesting the global dissemination of the ST-1 clone (SI Appendix, Fig. S4).…”

“…GBS is divided into 10 serotypes based on the carbohydrate composition of its sialic acid containing capsule, but gene content at the genomic level does not necessarily correlate with capsular serotype (8,9). A seven-gene multilocus sequence typing (MLST) allows for the classification of the majority of GBS strains isolated from humans into five major clonal complexes (CCs) with a recent study by Da Cunha et al showing that the major GBS CCs are primarily derived from a limited number of tetracycline-resistant clones, suggesting a key role of tetracycline resistance in GBS strain emergence (10,11). CC-17 GBS strains have been particularly well studied given their role as the major cause of severe, invasive infant disease (10,12).…”

“…A seven-gene multilocus sequence typing (MLST) allows for the classification of the majority of GBS strains isolated from humans into five major clonal complexes (CCs) with a recent study by Da Cunha et al showing that the major GBS CCs are primarily derived from a limited number of tetracycline-resistant clones, suggesting a key role of tetracycline resistance in GBS strain emergence (10,11). CC-17 GBS strains have been particularly well studied given their role as the major cause of severe, invasive infant disease (10,12). In contrast, serotype V strains cause a larger percentage of invasive disease in nonpregnant adults compared with neonates (13)(14)(15).…”