Genome-Wide Screens Identify Group A Streptococcus Surface Proteins Promoting Female Genital Tract Colonization and Virulence

Streptococcus pyogenes genes that promote pharyngitis in primates

“…Our findings provide extensive new information about the genes that contribute to GAS fitness in the URT of primates. This research also complements work conducted with other transposon mutant screens, including those designed to identify GAS genes contributing to growth in vitro, human saliva and blood ex vivo, and animal (mouse and NHP) models of soft tissue infection, muscle infection, and genital tract infection (29)(30)(31)(32)(33). The discoveries presented herein may ultimately lead to better prevention and treatment of GAS pharyngitis.…”

“…In aggregate, 698 fitness genes were identified. These identified fitness genes encode many known GAS virulence factors, such as C5a peptidase (ScpA) (51, 52), streptococcal inhibitor of complement (Sic) (53,54), antiphagocytic M protein (55), secreted DNAses (Spd, Spd3, and SdaD2) (45,56,57), surface-exposed adhesins and invasins (SclA, Enn, serum opacity factor [Sof], Streptococcus pyogenes adhesion and division [SpyAD], and EftLSLB) (33,(58)(59)(60)(61)(62)(63), and secreted toxins (SpeJ, SpeG, and SpyA) (49, 64) ( Figure 1). A common set of 115 genes was found to be important for GAS fitness for both M1 and M28 organisms ( Figure 1 and Supplemental Table 3).…”

“…These include M protein (emm1) (79,80), streptococcal C5a peptidase (scpA), serum opacity factor (sof) (81), and SpyAD (spyAD). Importantly, we recently reported that SpyAD is also crucial for GAS virulence during necrotizing myositis and female genital tract infections in NHPs (32,33). The critical roles in multiple infection models suggest SpyAD could be an attractive vaccine target (62,82).…”

“…As an alternative strategy, which does not require the animal to be sacrificed, we collected and pooled 10 swabs from the posterior oropharynx of each animal. We used an identical 10-swab strategy in our recent successful cynomolgus macaque female genital tract TraDIS study (33). The high number of recovered CFU indicates that the output mutant pools are likely representative of the in vivo condition.…”

“…The results of these types of genetic studies can assist translational research efforts, including development of vaccines and therapeutics. Genome-wide transposon mutagenesis screens have been successfully used to identify novel GAS genes contributing to fitness in human blood and saliva ex vivo, in mouse subcutaneous infection, and in nonhuman primate (NHP) necrotizing myositis and female urogenital tract infection (28)(29)(30)(31)(32)(33). However, a genome-wide investigation of the GAS factors contributing to primate pharyngitis has not been conducted using transposon mutagenesis strategies.…”