Improved characterisation of MRSA transmission using within-host bacterial sequence diversity

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) transmission in the hospital setting has been a frequent subject of investigation using bacterial genomes, but previous approaches have not yet fully utilised the extra deductive power provided when multiple pathogen samples are acquired from each host. Here, we used a large dataset of MRSA sequences from multiply-sampled patients to reconstruct colonisation of individuals in a high-transmission setting in a hospital in Thailand. We reconstructed transmission trees for MRSA. We also investigated transmission between anatomical sites on the same individual, finding that this either occurs repeatedly or involves a wide transmission bottleneck. We examined the between-subject bottleneck, finding considerable variation in the amount of diversity transmitted. Finally, we compared our approach to the simpler method of identifying transmission pairs using single nucleotide polymorphism (SNP) counts. This suggested that the optimum threshold for identifying a pair is 39 SNPs, if sensitivities and specificities are equally weighted.

Modeling MRSA decolonization: Interactions between body sites and the impact of site-specific clearance

“…The importance of the nares has previously been noted in data from an intensive care unit[22]. However, the added value of decolonization efforts that focus on body sites other than the nares is not well understood.…”

Longitudinal whole-genome based comparison of carriage and infection associated Staphylococcus aureus in northern Australian dialysis clinics

“…Detailed studies of potential transmission events of a single ST of S. aureus have suggested 30 SNPs [23] and 39 SNPs [24] as thresholds for genome identity when closely related isolates are compared. As we undertook alignment of all of the sequenced isolates from this study to a PLOS ONE single reference genome of ST5, we compared our empirically calculated cut off value of �5 SNPs for genome non-discrimination from the full orthologous SNP matrix, to more detailed single ST analyses that more closely reflect the published studies.…”

Molecular epidemiology in current times

“…In 2020, hundreds of papers have been monthly published which apply molecular techniques to resolve the epidemiology of infectious diseases. To illustrate the increasing impact of whole genome sequencing in the surveillance of infectious disease, I arbitrarily picked the themes of recently published papers of clinically important pathogens co‐authored by infectious disease specialists and genome researchers from the Wellcome Sanger Institute: Definition of a quality metrics for the sequencing of methicillin‐resistant Staphylococcus aureus (MRSA) in clinical practice (Raven et al ., 2020) Assessment of the feasibility and utility of adding genomics to epidemiological surveillance of MRSA associated with bloodstream infection to determine the national population structure of MRSA, contextualize previous outbreaks and detect high‐risk lineages (Toleman et al ., 2019) Rapid sequencing of MRSA direct from clinical plates in a routine microbiology laboratory (Blane et al ., 2019) Evaluation of a fully automated bioinformatics system for analysis of MRSA genomes and detection of outbreaks (Brown et al ., 2019) Reconstruction of transmission trees for MRSA in a high‐transmission hospital setting including tracing of an individual at different anatomical sites (Hall et al ., 2019) Longitudinal genomic surveillance of community‐ and hospital‐associated MRSA lineages in the United Kingdom (Coll et al ., 2017) Evolutionary history and genomic epidemiology of the origins and global spread of a multidrug‐resistant, community‐associated S. aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772) (Steinig et al ., 2019) Emergence of a new Streptococcus pyogenes lineage in England associated with an increased incidence of scarlet fever and invasive disease (Lynskey et al ., 2019) Longitudinal population dynamics and antimicrobial resistance mechanisms in Klebsiella pneumoniae and Enterobacter cloacae between 2007 and 2012 in a major UK hospital (Ellington et al ., 2019) Population genomics of K. pneumoniae in patients, livestock and environment in the East of England (Ludden et al ., 2020) Prevalence of vancomycin‐resistant Enterococcus faecium lineages in humans, livestock, hospitals and municipal wastewater treatment plants (Gouliouris et al ., 2018; 2019) Genomic history of the Vibrio cholera epidemics in Africa and the Americas (Domman et al ., 2017; Weill et al ., 2017) …”