Poster Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

Investigating host-dependent antibiotic resistance in Streptococcus pyogenes (#207)

Bonnie L Hyatt 1 , M Kalindu D Rodrigo 1 , Janessa Pickering 1 2 , August Mikucki 1 2 , Timothy C Barnett 1 2
  1. Wesfarmers Centre of Vaccines and Infectious Diseases, The Kids Research Institute Australia, University of Western Australia, Perth, WA, Australia
  2. The Marshall Centre for Infectious Disease Research and Training, School of Biomedical Science, University of Western Australia, Perth, WA, Australia

Background and Aims: Previous studies have suggested that current phenotypic in vitro antibiotic susceptibility tests produce misleading results and bacteria can utilise the host environment to bypass the effect of some antibiotics (1–3). In this study we have investigated the role of factors likely to be present in the host for their ability to alter antibiotic susceptibility profiles of Streptococcus pyogenes.

Methods: To identify phenotypic changes in antibiotic susceptibility, Epsilometer tests, antibiotic broth microdilution assays and checkerboard assays supplemented with host factors (e.g. metabolites and commensal supernatant) were used.

Results: Supplementation of growth media with host factors did have considerable effects on antibiotic susceptibly profiles. S. pyogenes isolates that appeared susceptible to trimethoprim, erythromycin or penicillin on standard antibiotic susceptibility test media (Mueller Hinton Agar) became resistant when the same media was supplemented with a range of host factors.

Conclusion and Significance: This study has identified that host factors can have profound effects on antibiotic susceptibility. In addition, the results may explain why S. pyogenes infections relapse. Future work will help to develop in vitro antibiotic susceptibility tests that can account for host factors and therefore prevent antibiotic treatment failure.

 

  1. 1. Kubicek-Sutherland JZ, Heithoff DM, Ersoy SC, Shimp WR, House JK, Marth JD, et al. Host-dependent Induction of Transient Antibiotic Resistance: A Prelude to Treatment Failure. EBioMedicine. 2015/10/27. 2015;2(9):1169–78.
  2. 2. Ersoy SC, Heithoff DM, Barnes L, Tripp GK, House JK, Marth JD, et al. Correcting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing. EBioMedicine. 2017 Jun 1;20:173–81.
  3. 3. Rodrigo MKD, Saiganesh A, Hayes AJ, Wilson AM, Anstey J, Pickering JL, et al. Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter. Nat Commun. 2022/12/01. 2022;13(1):6557.