Defining the phylogenetics and resistome of the major Clostridioides difficile ribotypes circulating in Australia

Keeley O'Grady; Stacey Hong; Papanin Putsathit; Narelle George; Christine Hemphill; Peter G Huntington; Tony M Korman; Despina Kotsanas; Monica Lahra; Rodney McDougall; Andrew McGlinchey; Avram Levy; Casey V Moore; Graeme Nimmo; Louise Prendergast; Jennifer Robson; David J Speers; Lynette Waring; Michael C Wehrhahn; Gerhard F Weldhagen; Richard M Wilson; Thomas V Riley; Daniel R Knight

doi:10.1099/mgen.0.001232

Defining the phylogenetics and resistome of the major Clostridioides difficile ribotypes circulating in Australia

Microb Genom. 2024 May;10(5). doi: 10.1099/mgen.0.001232.

Authors

Keeley O'Grady¹, Stacey Hong², Papanin Putsathit³, Narelle George⁴, Christine Hemphill⁵, Peter G Huntington⁶, Tony M Korman⁷, Despina Kotsanas⁸, Monica Lahra⁹, Rodney McDougall¹⁰, Andrew McGlinchey⁵, Avram Levy¹¹, Casey V Moore¹², Graeme Nimmo⁴, Louise Prendergast⁵, Jennifer Robson¹⁰, David J Speers^{11

13}, Lynette Waring⁵, Michael C Wehrhahn¹⁴, Gerhard F Weldhagen¹², Richard M Wilson¹⁵, Thomas V Riley^{1

11

16

3}, Daniel R Knight^{11

16}

Affiliations

¹ Centre for Biosecurity and One Health, Harry Butler Institute, Murdoch University, Murdoch, Western Australia, Australia.
² Communicable Disease Control Directorate, WA Department of Health, East Perth, Western Australia, Australia.
³ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
⁴ Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
⁵ Melbourne Pathology, Collingwood, Victoria, Australia.
⁶ Department of Microbiology, NSW Health Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
⁷ Monash University, Monash Health, Clayton, Victoria, Australia.
⁸ Monash Infectious Diseases, Monash Health, Monash Medical Centre, Clayton, Victoria, Australia.
⁹ Department of Microbiology, The Prince of Wales Hospital, Randwick, New South Wales, Australia.
¹⁰ Sullivan Nicolaides Pathology, Taringa, Queensland, Australia.
¹¹ Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, Western Australia, Australia.
¹² Microbiology and Infectious Diseases Laboratories, SA Pathology, Adelaide, South Australia, Australia.
¹³ School of Medicine, The University of Western Australia, Nedlands, Western Australia, Australia.
¹⁴ Douglass Hanly Moir Pathology, Macquarie Park, New South Wales, Australia.
¹⁵ Australian Clinical Labs, Microbiology Department, Wayville, South Australia, Australia.
¹⁶ School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia.

PMID: 38717815
DOI: 10.1099/mgen.0.001232

Abstract

Clostridioides difficile infection (CDI) remains a significant public health threat globally. New interventions to treat CDI rely on an understanding of the evolution and epidemiology of circulating strains. Here we provide longitudinal genomic data on strain diversity, transmission dynamics and antimicrobial resistance (AMR) of C. difficile ribotypes (RTs) 014/020 (n=169), 002 (n=77) and 056 (n=36), the three most prominent C. difficile strains causing CDI in Australia. Genome scrutiny showed that AMR was uncommon in these lineages, with resistance-conferring alleles present in only 15/169 RT014/020 strains (8.9 %), 1/36 RT056 strains (2.78 %) and none of 77 RT002 strains. Notably, ~90 % of strains were resistant to MLS_B agents in vitro, but only ~5.9 % harboured known resistance alleles, highlighting an incongruence between AMR genotype and phenotype. Core genome analyses revealed all three RTs contained genetically heterogeneous strain populations with limited evidence of clonal transmission between CDI cases. The average number of pairwise core genome SNP (cgSNP) differences within each RT group ranged from 23.3 (RT056, ST34, n=36) to 115.6 (RT002, ST8, n=77) and 315.9 (RT014/020, STs 2, 13, 14, 49, n=169). Just 19 clonal groups (encompassing 40 isolates), defined as isolates differing by ≤2 cgSNPs, were identified across all three RTs (RT014/020, n=14; RT002, n=3; RT056, n=2). Of these clonal groups, 63 % (12/19) comprised isolates from the same Australian State and 37 % (7/19) comprised isolates from different States. The low number of plausible transmission events found for these major RTs (and previously documented populations in animal and environmental sources/reservoirs) points to widespread and persistent community sources of diverse C. difficile strains as opposed to ongoing nationwide healthcare outbreaks dominated by a single clone. Together, these data provide new insights into the evolution of major lineages causing CDI in Australia and highlight the urgent need for enhanced surveillance, and for public health interventions to move beyond the healthcare setting and into a One Health paradigm to effectively combat this complex pathogen.

Keywords: AMR; Clostridioides difficile; WGS; epidemiology; microbial genomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Australia / epidemiology
Clostridioides difficile* / classification
Clostridioides difficile* / drug effects
Clostridioides difficile* / genetics
Clostridioides difficile* / isolation & purification
Clostridium Infections* / epidemiology
Clostridium Infections* / microbiology
Clostridium Infections* / transmission
Drug Resistance, Bacterial / genetics
Genome, Bacterial
Genotype
Humans
Phylogeny*
Polymorphism, Single Nucleotide
Ribotyping*

Substances

Anti-Bacterial Agents