Emergence of High-Level Gentamicin Resistance in Streptococcus agalactiae Hypervirulent Serotype IV ST1010 (CC452) Strains by Acquisition of a Novel Integrative and Conjugative Element.

Streptococcus agalactiae (group B streptococci, GBS) is responsible for severe infections in both neonates and adults. Currently, empiric antimicrobial therapy for sepsis and meningitis is the combined use of penicillin and gentamicin due to the enhanced bactericidal activity. However, high-level gentamicin resistance (HLGR) abrogates the synergism. The rate of HLGR was investigated within a dataset of 433 GBS strains collected from cases of invasive disease in both adults and neonates as well as from pregnant carriers. GBS isolates (n = 20, 4.6%) presented with HLGR (gentamicin MIC breakpoint >1024 mg/L) that was differently diffused between strains from adults or neonates (5.2% vs. 2.8%). Notably, 70% of HLGR GBS strains (14 isolates) were serotype IV. Serotype IV HLGR-GBS isolates were susceptible to all antibiotics tested, exhibited the alpha-C/HvgA/PI-2b virulence string, and belonged to sequence type 1010 (clonal complex (CC) 452). The mobile element that harbored the HLGR aac(6')-aph(2)″ gene is a novel integrative and conjugative element (ICE) about 45 kb long, derived from GBS 515 ICE tRNALys. The clonal expansion of this HLGR hypervirulent serotype IV GBS CC452 sublineage may pose a threat to the management of infections caused by this strain type.

Long-Term Co-Circulation of Host-Specialist and Host-Generalist Lineages of Group B Streptococcus in Brazilian Dairy Cattle with Heterogeneous Antimicrobial Resistance Profiles.

Group B Streptococcus (GBS) is a major cause of contagious bovine mastitis (CBM) in Brazil. The GBS population is composed of host-generalist and host-specialist lineages, which may differ in antimicrobial resistance (AMR) and zoonotic potential, and the surveillance of bovine GBS is crucial to developing effective CBM control and prevention measures. Here, we investigated bovine GBS isolates (n = 156) collected in Brazil between 1987 and 2021 using phenotypic testing and whole-genome sequencing to uncover the molecular epidemiology of bovine GBS. Clonal complex (CC) 61/67 was the predominant clade in the 20th century; however, it was replaced by CC91, with which it shares a most common recent ancestor, in the 21st century, despite the higher prevalence of AMR in CC61/67 than in CC91, and high selection pressure for AMR from indiscriminate antimicrobial use in the Brazilian dairy industry. CC103 also emerged as a dominant CC in the 21st century, and a considerable proportion of herds had two or more GBS strains, suggesting poor biosecurity and within-herd evolution due to the chronic nature of CBM problems. The majority of bovine GBS belonged to serotype Ia or III, which was strongly correlated with CCs. Ninety-three isolates were resistant to tetracycline (≥8 µg/mL; tetO = 57, tetM = 34 or both = 2) and forty-four were resistant to erythromycin (2.0 to >4 µg/mL; ermA = 1, ermB = 38, mechanism unidentified n = 5). Only three isolates were non-susceptible to penicillin (≥8.0 µg/mL), providing opportunities for improved antimicrobial stewardship through the use of narrow-spectrum antimicrobials for the treatment of dairy cattle. The common bovine GBS clades detected in this study have rarely been reported in humans, suggesting limited risk of interspecies transmission of GBS in Brazil. This study provides new data to support improvements to CBM and AMR control, bovine GBS vaccine design, and the management of public health risks posed by bovine GBS in Brazil.

Genomic Analysis Reveals New Integrative Conjugal Elements and Transposons in GBS Conferring Antimicrobial Resistance.

Streptococcus agalactiae or group B streptococcus (GBS) is a leading cause of neonatal sepsis and increasingly found as an invasive pathogen in older patient populations. Beta-lactam antibiotics remain the most effective therapeutic with resistance rarely reported, while the majority of GBS isolates carry the tetracycline resistance gene tet(M) in fixed genomic positions amongst five predominant clonal clades. In the UK, GBS resistance to clindamycin and erythromycin has increased from 3% in 1991 to 11.9% (clindamycin) and 20.2% (erythromycin), as reported in this study. Here, a systematic investigation of antimicrobial resistance genomic content sought to fully characterise the associated mobile genetic elements within phenotypically resistant GBS isolates from 193 invasive and non-invasive infections of UK adult patients collected during 2014 and 2015. Resistance to erythromycin and clindamycin was mediated by erm(A) (16/193, 8.2%), erm(B) (16/193, 8.2%), mef(A)/msr(D) (10/193, 5.1%), lsa(C) (3/193, 1.5%), lnu(C) (1/193, 0.5%), and erm(T) (1/193, 0.5%) genes. The integrative conjugative elements (ICEs) carrying these genes were occasionally found in combination with high gentamicin resistance mediating genes aac(6')-aph(2″), aminoglycoside resistance genes (ant(6-Ia), aph(3'-III), and/or aad(E)), alternative tetracycline resistance genes (tet(O) and tet(S)), and/or chloramphenicol resistance gene cat(Q), mediating resistance to multiple classes of antibiotics. This study provides evidence of the retention of previously reported ICESag37 (n = 4), ICESag236 (n = 2), and ICESpy009 (n = 3), as well as the definition of sixteen novel ICEs and three novel transposons within the GBS lineage, with no evidence of horizontal transfer.

Molecular epidemiology of Streptococcus agalactiae in non-pregnant populations: a systematic review.

Streptococcus agalactiae (group B Streptococcus, GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards its containment among pregnant women and neonates. This systematic review assessed the molecular epidemiology and compared how the lineages circulating among non-pregnant populations relate to those of pregnant and neonatal populations worldwide. A systematic search was performed across nine databases from 1 January 2000 up to and including 20 September 2021, with no language restrictions. The Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool (PCAT) was used to assess the quality of included studies. The global population structure of GBS from the non-pregnant population was analysed using in silico typing and phylogenetic reconstruction tools. Twenty-four articles out of 13 509 retrieved across 9 databases were eligible. Most studies were conducted in the World Health Organization European region (12/24, 50 %), followed by the Western Pacific region (6/24, 25 %) and the Americas region (6/24, 25 %). Serotype V (23%, 2310/10240) and clonal complex (CC) 1 (29 %, 2157/7470) were the most frequent serotype and CC, respectively. The pilus island PI1 : PI2A combination (29 %, 3931/13751) was the most prevalent surface protein gene, while the tetracycline resistance tetM (55 %, 5892/10624) was the leading antibiotic resistance gene. This study highlights that, given the common serotype distribution identified among non-pregnant populations (V, III, Ia, Ib, II and IV), vaccines including these six serotypes will provide broad coverage. The study indicates advanced molecular epidemiology studies, especially in resource-constrained settings for evidence-based decisions. Finally, the study shows that considering all at-risk populations in an inclusive approach is essential to ensure the sustainable containment of GBS.

Identifying large-scale recombination and capsular switching events in Streptococcus agalactiae strains causing disease in adults in the UK between 2014 and 2015.

Cases of invasive group B streptococcal infection in the adult UK population have steadily increased over recent years, with the most common serotypes being V, III and Ia, but less is known of the genetic background of these strains. We have carried out in-depth analysis of the whole-genome sequences of 193 clinically important group B Streptococcus (GBS) isolates (184 were from invasive infection, 8 were from non-invasive infection and 1 had no information on isolation site) isolated from adults and submitted to the National Reference Laboratory at the UK Health Security Agency between January 2014 and December 2015. We have determined that capsular serotypes III (26.9%), Ia (26.4%) and V (15.0%) were most commonly identified, with slight differences in gender and age distribution. Most isolates (n=182) grouped to five clonal complexes (CCs), CC1, CC8/CC10, CC17, CC19 and CC23, with common associations between specific serotypes and virulence genes. Additionally, we have identified large recombination events mediating potential capsular switching events between sequence type (ST)1 serotype V and serotypes Ib (n=2 isolates), II (n=2 isolates) and VI (n=2 isolates); between ST19 serotype III and serotype V (n=5 isolates); and between CC17 serotype III and serotype IV (n=1 isolate). The high genetic diversity of disease-causing isolates and multiple recombination events reported in this study highlight the need for routine surveillance of the circulating disease-causing GBS strains. This information is crucial to better understand the global spread of GBS serotypes and genotypes, and will form the baseline information for any future GBS vaccine research in the UK and worldwide.