Genomic analyses of Streptococcus mitis and its role as an oral commensal, pathogen, and reservoir of antimicrobial resistance for Streptococcus pneumoniae through horizontal gene transfer.
Doctoral thesis (Ph.D), UCL (University College London).
Access restricted to UCL open access staff until 1 December 2022.
Streptococcus mitis is a neglected oral commensal and opportunistic pathogen that is closely related to the global pathogen S. pneumoniae. However, S. mitis has been shown to be a source of AMR for the pneumococcus through horizontal gene transfer (HGT). It is unclear to what extent S. mitis acts as a source of AMR for emerging resistant pneumococcal lineages in context of selective pressure from antibiotics and vaccines.
This thesis summarises genomic findings from global S. mitis datasets obtained from carriage and invasive disease. A comprehensive HGT analysis of global S. mitis and pneumococcal carriage isolates revealed that S. mitis contributes to reduced Beta-lactam (β-lactam) susceptibility among commonly carried pneumococcal serotypes that are associated with long carriage duration through HGT. S. mitis was shown to be abundant in the oral cavity of young Malawian children and co-carriage with the pneumococcus was high in the region demonstrating the opportunities for interspecies contact. S. mitis isolates found in carriage and expired respiratory secretions of healthy individuals were shown to harbour AMR genes, and potential S. mitis transmission was identified. Overall, distinct S. mitis populations have been identified that differ in respect to the presence of pneumococcal virulence genes, however, S. mitis isolates that caused infective endocarditis in the UK between 2001 to 2016 were from diverse populations.
Together, this snapshot of S. mitis has revealed that the species is more than a commensal, but a highly diverse and complex species that is abundant, has a high prevalence of AMR genes, can potentially be transmitted through respiratory shedding, and is an important source of AMR for the pneumococcus. Therefore, in regions such as Malawi where S. mitis and S. pneumoniae co-carriage is high, it will be important to monitor the influence of AMR HGT from S. mitis and other commensal streptococci.
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