Poster Presentation BacPath 2024

Microevolution associated with clonal expansion of a hypervirulent, penicillin resistant lineage of Neisseria meningitidis in rural Western Australia (#84)

August Mikucki 1 , Eng Guan Chua 1 , Alfred Chin Yen Tay 1 , Michael Wise 1 , Geoffrey W Coombs 2 3 , David Speers 3 , Shakeel Mowlaboccus 2 3 , Charlene M Kahler 1
  1. The Marshall Center for Infectious Diseases Research and Training, School of Biomedical Science, University of Western Australia, Perth
  2. Antimicrobial Resistance and Infectious Diseases Research Laboratory, School of Medical, Molecular and Forensic Sciences, Murdoch University, Perth, Western Australia, Australia
  3. Pathwest Laboratory Medicine WA, Perth, Western Australia, Australia

Neisseria meningitidis is a coloniser of the human nasopharynx which occasionally causes invasive meningococcal disease. Despite numerous reports of resistant isolates, antimicrobial resistant meningococcal clones have historically not persisted over long time periods nor on a global scale, presumably due to the imposed fitness cost associated with resistance. One exception is a penicillin-resistant clade of serogroup W clonal complex 11 (MenW:cc11) isolates first identified in Western Australia which have since caused disease globally. Here, we investigated genomic changes associated with resistance in these isolates in the context of the Western Australian outbreak (2013-2020). Seventy-six MenW:cc11 isolates were retrieved from meningococcal disease cases and underwent short-read sequencing. Reference genomes were generated for three isolates. In accordance with previous analysis, two clusters were apparent: cluster A (12 isolates, PenS) and cluster B (63 isolates, PenR). Within cluster B, we found significant support (p<0.01) for clonal expansion of a subclade unique to Australia which we named cluster B2 (50/63 isolates). Genomic comparison of cluster A and cluster B1 (13 isolates) revealed 128 allelic differences including changes to genes involved in cell wall regulation, pilus biogenesis, and the MtrR transcriptional regulator. Clonal expansion of cluster B2 was associated with 60 allelic changes including genes involved in core metabolism, coenzyme biosynthesis, and the pilus adhesins PilC1 and PilC2. In a search of the pubMLST Neisseria database, all allelic changes associated with cluster B1 were found exclusively in other hypervirulent lineages, whereas half (6/12) of the regions of recombination in cluster B2 isolates were present in contemporary Australian commensal lineages. Taken together, these data suggest the global success of these isolates is due to compensatory mutations acquired through horizontal exchange with other hypervirulent lineages and that subsequent adaptation of the lineage to the local Australian host population allowed the persistence and spread of cluster B2.