Oral Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

How Streptococcus agalactiae subverts intoxication by zinc or copper (113718)

Matthew J. Sullivan 1 2 , Ignacio Teran 1 , Kelvin Goh 3 , Glen C. Ulett 3 4
  1. School of Biological Sciences, University of East Anglia, Norwich, United Kingdom
  2. Centre for Microbial Interactions, Norwich Research Park, Norwich, United Kingdom
  3. School of Pharmacy and Medical Science, Griffith University, Gold Coast, Queensland, Australia
  4. Institute of Biomedicine and Glycomics, Griffith University, Gold Coast, Queensland, Australia

Copper (Cu) and zinc (Zn) are mobilised by phagocytes in the host and used as potent antimicrobials to intoxicate invading bacterial pathogens. Streptococcus agalactiae is an opportunistic pathogen that causes fatal infections in neonates and survives inside macrophages as ‘trojan horses’ during colonisation of the reproductive tract [1]. Defined resistance mechanisms are used by streptococci and other bacteria to subvert intoxication by metals, which typically comprise efflux pumps that expel Cu [2] and Zn [3] from the bacterial cell and limit intracellular accumulation. Although efflux is considered the primary mechanism of metal resistance, our recent work in S. agalactiae has highlighted alternative pathways that have major contributions to surviving metal stress [4]. Using a combination of transcriptomics and transposon-directed insertion sequencing, we identified novel sets of genes conferring a survival advantage [5, 6], including metabolic pathways and processes that were not previously linked to metal stress. Molecular characterisation of these targets has revealed a remarkable interplay between certain metabolites and metal resistance, including the identification of pathways that inhibit or enhance the ability of S. agalactiae to survive metal intoxication. These insights broaden the horizons for research into mechanisms of metal ion resistance in streptococci and beyond.

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  2. [2] Sullivan MJ, KGK Goh, D Gosling, L Katupitiya, and GC Ulett (2021) J Bacteriol 203 (19) e0031521 https://doi.org/10.1128/JB.00315-21.
  3. [3] Sullivan MJ, KGK Goh, and GC Ulett (2021) mSphere 6 (3) e00105-21 https://doi.org/10.1128/mSphere.00105-21.
  4. [4] Sullivan MJ, I Teran, KGK Goh, and GC Ulett (2024) Emerg Top Life Sci 8 (1) 45-56 https://doi.org/10.1042/ETLS20230115.
  5. [5] Sullivan MJ, KGK Goh, and GC Ulett (2022) PLoS Pathog 18 (7) e1010607 https://doi.org/10.1371/journal.ppat.1010607.