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

Uzma Basit Khan, Edward A R Portal, Kirsty Sands, Stephanie Lo, Victoria J Chalker, Elita Jauneikaite, Owen B Spiller

Research output: Contribution to journalArticlepeer-review

6 Citations (SciVal)

Abstract

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.

Original languageEnglish
Article number544
Number of pages16
JournalAntibiotics
Volume12
Issue number3
DOIs
Publication statusPublished - 9 Mar 2023

Bibliographical note

Funding Information:
The authors would like to thank UKHSA reference laboratory colleagues, led by Juliana Coelho, for provision of isolates, sequences, and metadata. This publication made use of the PubMLST website ( https://pubmlst.org/ , accessed on 15 December 2022) developed by Keith Jolley (Jolley and Maiden 2010, BMC Bioinformatics, 11:595) and cited at the University of Oxford. The development of the website was funded by the Wellcome Trust. E.J. is a Rosetrees/Stoneygate 2017 Imperial College Research Fellow, funded by Rosetrees Trust and the Stoneygate Trust (Fellowship no. M683). E.J. is affiliated with the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London in partnership with the UK Health Security Agency (previously PHE), in collaboration with Imperial Healthcare Partners, University of Cambridge, and University of Warwick.

Publisher Copyright:
© 2023 by the authors.

Keywords

  • clonal complex (CC)
  • group B streptococcus
  • integrative conjugative element (ICE)
  • macrolide resistance
  • mobile genetic elements

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)
  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Microbiology

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