Dataset Information

Genome Evolution of Invasive Methicillin-Resistant Staphylococcus aureus in the Americas.

ABSTRACT: Staphylococcus aureus causes a variety of debilitating and life-threatening diseases, and thus remains a challenging global health threat. S. aureus is remarkably diverse, yet only a minority of methicillin-resistant S. aureus (MRSA) clones have caused pandemic proportions of diseases. The genetic drivers of the successful dissemination of some clones across wide geographical expanses remain poorly understood. We analyzed 386 recently published MRSA genomes from bloodstream infections sampled in North, Central, and South America from 2011 to 2018. Here, we show that MRSA-associated bloodstream infections were attributable to two genetically distinct lineages. One lineage consisted almost exclusively of sequence type (ST) 8, which emerged in 1964. A second lineage emerged in 1986 and consisted of STs 5, 105, and 231. The two lineages have simultaneously disseminated across geographically distant sites. Sublineages rapidly diverged within locations in the early 2000s. Their diversification was associated with independent acquisitions of unique variants of the mobile mecA-carrying chromosomal cassette and distinct repertoires of antimicrobial resistance genes. We show that the evolution and spread of invasive multidrug-resistant MRSA in the Americas was driven by transcontinental dissemination, followed by more recent establishment and divergence of local pathogen populations. Our study highlights the need for continued international surveillance of high-risk clones to control the global health threat of multidrug resistance. IMPORTANCE Bloodstream infections due to S. aureus cause significant patient morbidity and mortality worldwide, exacerbated by the emergence and spread of methicillin resistant S. aureus (MRSA). This study provides important insights on the evolution and long-distance geographic expansion of two distinct MRSA lineages that predominate in bloodstream infections in the past 5 decades. The success of these two lineages partly lies on their acquisition of a diverse set of antimicrobial resistance genes and of unique variants of the mobile genetic element SCCmec that carries the gene mecA conferring resistance to beta-lactams. High-risk antimicrobial resistant clones can therefore rapidly disseminate across long distances and establish within local communities within a short period of time. These results have important implications for global initiatives and local epidemiological efforts to monitor and control invasive MRSA infections and transcontinental spread of multidrug resistance.

SUBMITTER: Smith JT

PROVIDER: S-EPMC9241880 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:UNLABELLED:Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations. IMPORTANCE:With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.

Project description:ImportanceEstimating the US burden of methicillin-resistant Staphylococcus aureus (MRSA) infections is important for planning and tracking success of prevention strategies.ObjectiveTo describe updated national estimates and characteristics of health care- and community-associated invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in 2011.Design, setting, and participantsActive laboratory-based case finding identified MRSA cultures in 9 US metropolitan areas from 2005 through 2011. Invasive infections (MRSA cultured from normally sterile body sites) were classified as health care-associated community-onset (HACO) infections (cultured ≤ 3 days after admission and/or prior year dialysis, hospitalization, surgery, long-term care residence, or central vascular catheter presence ≤ 2 days before culture); hospital-onset infections (cultured >3 days after admission); or community-associated infections if no other criteria were met. National estimates were adjusted using US census and US Renal Data System data.Main outcomes and measuresNational estimates of invasive HACO, hospital-onset, and community-associated MRSA infections using US census and US Renal Data System data as the denominator.ResultsAn estimated 80,461 (95% CI, 69,515-93,914) invasive MRSA infections occurred nationally in 2011. Of these, 48,353 (95% CI, 40,195-58,642) were HACO infections; 14,156 (95% CI, 10,096-20,440) were hospital-onset infections; and 16,560 (95% CI, 12,806-21,811) were community-associated infections. Since 2005, adjusted national estimated incidence rates decreased among HACO infections by 27.7% and hospital-onset infections decreased by 54.2%; community-associated infections decreased by only 5.0%. Among recently hospitalized community-onset (nondialysis) infections, 64% occurred 3 months or less after discharge, and 32% of these were admitted from long-term care facilities.Conclusions and relevanceAn estimated 30,800 fewer invasive MRSA infections occurred in the United States in 2011 compared with 2005; in 2011 fewer infections occurred among patients during hospitalization than among persons in the community without recent health care exposures. Effective strategies for preventing infections outside acute care settings will have the greatest impact on further reducing invasive MRSA infections nationally.

Dataset Information

Genome Evolution of Invasive Methicillin-Resistant Staphylococcus aureus in the Americas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets