Abstract
Over the last decade, an increasing number of infections with livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (LA-MRSA CC398) in persons without contact to livestock has been registered in Denmark. These infections have been suggested to be the result of repeated spillover of random isolates from livestock into the community. However, other studies also found emerging sub-lineages spreading among humans. Based on genome-wide SNPs and genome-wide association studies (GWAS), we assessed the population structure and genomic content of Danish LA-MRSA CC398 isolates from healthcare-associated infections from 2014 to 2016 (n = 73) and compared these to isolates from pigs in Denmark from 2014 (n = 183). Phylogenetic analyses showed that most human isolates were closely related to and scattered among pig isolates showing that the majority of healthcare-associated infections are the result of repeated spillover from pig farms, even though cases of human-to-human transmission also were identified. GWAS revealed frequent loss of antimicrobial resistance genes and acquisition of human-specific virulence genes in the human isolates showing adaptation in response to changes in selective pressures in different host environments, which over time could lead to the emergence of LA-MRSA CC398 lineages more adapted to human colonization and transmission.
Highlights
Human infections with livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (LA-MRSA CC398) have increased dramatically over the last decade[1,2] and accounted for 16% of all MRSA infections in Denmark in 20163
The annual numbers of CO cases increased in parallel with the prevalence of LA-MRSA CC398 in pig farms (Fig. 1), while the annual numbers of HO and healthcare-associated community-onset (HACO) cases did not exceed seven and 21, respectively
This study shows that human LA-MRSA CC398 isolates from patients with healthcare-associated infections have their origin in pigs and that they are repeatedly introduced into healthcare facilities
Summary
Human infections with livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (LA-MRSA CC398) have increased dramatically over the last decade[1,2] and accounted for 16% of all MRSA infections in Denmark in 20163. Infections are categorized as healthcare-associated community-onset (HACO) if the patients have been admitted to a healthcare institution within the last 12 months before onset in the community Because most of these non-LO cases have no risk factors for MRSA carriage (e.g., livestock contact), they may inadvertently introduce the bacteria into hospitals and nursing homes. Recent studies report the emergence of sub-lineages spreading independently of the livestock reservoir[15,16] Such lineages could be better adapted to the human host, which increases the risk of spread into healthcare institutions via non-LO cases with the present guidelines. The aims of this study were to: (i) determine whether the introduction of LA-MRSA CC398 into healthcare institutions is due to repeated spillover of random isolates from livestock or to circulation of sub-lineages with an increased capacity for human colonization and transmission; and (ii) investigate relevant bacterial genomes for signatures of adaptation to the human host
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