RESUMEN
Streptococcus pyogenes is known to be associated with a variety of infections, from pharyngitis to necrotizing fasciitis (flesh-eating disease). S. pyogenes of the ST62/emm87 lineage is recognized as one of the most frequently isolated lineages of invasive infections caused by this bacterium, which may be involved in hospital outbreaks and cluster infections. Despite this, comparative genomic and phylogenomic studies have not yet been carried out for this lineage. Thus, its virulence and antimicrobial susceptibility profiles are mostly unknown, as are the genetic relationships and evolutionary traits involving this lineage. Previously, a strain of S. pyogenes ST62/emm87 (37-97) was characterized in our lab for its ability to generate antibiotic-persistent cells, and therapeutic failure in severe invasive infections caused by this bacterial species is well-reported in the scientific literature. In this work, we analyzed genomic and phylogenomic characteristics and evaluated the virulence and resistance profiles of ST62/emm87 S. pyogenes from Brazil and international sources. Here we show that strains that form this lineage (ST62/emm87) are internationally spread, involved in invasive outbreaks, and share important virulence profiles with the most common emm types of S. pyogenes, such as emm1, emm3, emm12, and emm69, which are associated with most invasive infections caused by this bacterial species in the USA and Europe. Accordingly, the continued increase of ST62/emm87 in severe S. pyogenes diseases should not be underestimated.
RESUMEN
Multidrug resistance is commonly acquired by transferring DNA from one bacterium to another. However, the mechanisms that enhance the acquisitions of foreign genes are poorly understood, as well as the dynamics of their transmission between hosts in different environments. Here, genomic approaches were applied to evaluate the enrichment of the S. aureus chromosome with resistance traits in groups of genomes with or without anti-restriction genes and to analyze some evolutionary aspects of these acquisitions. Furthermore, the role played by an anti-restriction gene in improving multiresistance in MRSA was investigated by molecular cloning. A strong association was observed between the presence of anti-restriction gene homologs and patterns of multidrug resistance. Human isolates, mainly ST239-SCCmecIII, carry ardA-H1, and from animal sources, mainly CC398, carry ardA-H2. Increased DNA transfer was observed for clones that express the ardA-H1 allele, corroborating its role in promoting gene transfer. In addition, ardA-H1 was expressed in the dsDNA format in the BMB9393 strain. The evolution of successful multidrug-resistant MRSA lineages of the ST239 and ST398 was initiated not only by the entry of the mec cassette but also by the acquisition of anti-restriction gene homologs. Understanding the mechanisms that affect DNA transfer may provide new tools to control the spread of drug resistance.
RESUMEN
The global spread of specific clones of methicillin-resistant Staphylococcus aureus (MRSA) has become a major public health problem, and understanding the dynamics of geographical spread requires worldwide surveillance. Over the past 20 years, the ST239 lineage of MRSA has been recognized as an emerging clone across the globe, with detailed studies focusing on isolates from Europe and Asia. Less is known about this lineage in South America, and, particularly, Brazil where it was the predominant lineage of MRSA in the early 1990s to 2000s. To gain a better understanding about the introduction and spread of ST239 MRSA in Brazil we undertook a comparative phylogenomic analysis of ST239 genomes, adding seven completed, closed Brazilian genomes. Brazilian ST239 isolates grouped in a subtree with those from South American, and Western, romance-language-speaking, European countries, here designated the South American clade. After an initial worldwide radiation in the 1960s and 1970s, we estimate that ST239 began to spread in South America and Brazil in approximately 1988. This clone demonstrates specific genomic changes that are suggestive of local divergence and adaptational change including agrC single-nucleotide polymorphisms variants, and a distinct pattern of virulence-associated genes (mainly the presence of the chp and the absence of sea and sasX). A survey of a geographically and chronologically diverse set of 100 Brazilian ST239 isolates identified this virulence genotype as the predominant pattern in Brazil, and uncovered an unexpectedly high prevalence of agr-dysfunction (30%). ST239 isolates from Brazil also appear to have undergone transposon (IS256) insertions in or near global regulatory genes (agr and mgr) that likely led to rapid reprogramming of bacterial traits. In general, the overall pattern observed in phylogenomic analyses of ST239 is of a rapid initial global radiation, with subsequent local spread and adaptation in multiple different geographic locations. Most ST239 isolates harbor the ardA gene, which we show here to have in vivo anti-restriction activity. We hypothesize that this gene may have improved the ability of this lineage to acquire multiple resistance genes and distinct virulence-associated genes in each local context. The allopatric divergence pattern of ST239 also may suggest strong selective pressures for specific traits in different geographical locations.
