Abstract
Although skin and soft tissue infections (SSTI) are the most common focal infections associated with invasive disease caused by Streptococcus pyogenes (Lancefield Group A streptococci - GAS), there is scarce information on the characteristics of isolates recovered from SSTI in temperate-climate regions. In this study, 320 GAS isolated from SSTI in Portugal were characterized by multiple typing methods and tested for antimicrobial susceptibility and SpeB activity. The covRS and ropB genes of isolates with no detectable SpeB activity were sequenced. The antimicrobial susceptibility profile was similar to that of previously characterized isolates from invasive infections (iGAS), presenting a decreasing trend in macrolide resistance. However, the clonal composition of SSTI between 2005 and 2009 was significantly different from that of contemporary iGAS. Overall, iGAS were associated with emm1 and emm3, while SSTI were associated with emm89, the dominant emm type among SSTI (19%). Within emm89, SSTI were only significantly associated with isolates lacking the hasABC locus, suggesting that the recently emerged emm89 clade 3 may have an increased potential to cause SSTI. Reflecting these associations between emm type and disease presentation, there were also differences in the distribution of emm clusters, sequence types, and superantigen gene profiles between SSTI and iGAS. According to the predicted ability of each emm cluster to interact with host proteins, iGAS were associated with the ability to bind fibrinogen and albumin, whereas SSTI isolates were associated with the ability to bind C4BP, IgA, and IgG. SpeB activity was absent in 79 isolates (25%), in line with the proportion previously observed among iGAS. Null covS and ropB alleles (predicted to eliminate protein function) were detected in 10 (3%) and 12 (4%) isolates, corresponding to an underrepresentation of mutations impairing CovRS function in SSTI relative to iGAS. Overall, these results indicate that the isolates responsible for SSTI are genetically distinct from those recovered from normally sterile sites, supporting a role for mutations impairing CovRS activity specifically in invasive infection and suggesting that this role relies on a differential regulation of other virulence factors besides SpeB.
Highlights
Streptococcus pyogenes is responsible for a variety of human infections ranging from mild and frequent diseases, such as pharyngitis and cutaneous infections, to more severe and rare invasive infections including sepsis, necrotizing fasciitis and streptococcal toxic shock syndrome (Walker et al, 2014)
Antimicrobial resistance among soft tissue infections (SSTI) isolates was not significantly different from that found among contemporary iGAS and pharyngitis isolates, with the decreasing resistance to macrolides in SSTI mirroring declines in resistance previously described among isolates causing these other infections (Friães et al, 2013b; Silva-Costa et al, 2015)
The studied SSTI isolates presented a very high genetic diversity, which was higher than the diversity of iGAS isolates in the period of 2005–2009
Summary
Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a variety of human infections ranging from mild and frequent diseases, such as pharyngitis and cutaneous infections, to more severe and rare invasive infections including sepsis, necrotizing fasciitis and streptococcal toxic shock syndrome (Walker et al, 2014). The gold-standard typing methodology of GAS is emm typing, which relies on the variability of the amino acid sequence of the N-terminal portion of S. pyogenes major virulence factor: the M protein (McMillan et al, 2013). The sequence of the 5′ variable region of the emm gene encoding the M protein determines the emm type, of which there are more than 250 distinct variants (https://www.cdc.gov/streplab/m-proteingenetyping.html). Emm typing is based on the sequence of only approximately 10–15% of the complete emm gene. A new classification was proposed based on emm clusters established by phylogenetic analysis of the entire sequence of the emm gene of 175 different emm types (Sanderson-Smith et al, 2014). Since isolates with the same emm type encode nearly identical M proteins, the emm cluster can be inferred from the emm type
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