Type VII secretion system and its effect on group B Streptococcus virulence in isolates obtained from newborns with early onset disease and colonized pregnant women

IntroductionGBS may cause a devastating disease in newborns. In early onset disease of the newborn the bacteria are acquired from the colonized mother during delivery. We characterized type VII secretion system (T7SS), exporting small proteins of the WXG100 superfamily, in group B Streptococci (GBS) isolates from pregnant colonized women and newborns with early onset disease (EOD) to better understand T7SS contribution to virulence in these different clinical scenarios.MethodsGBS genomes [N=33, 17 EOD isolates (serotype III/ST17) and 16 colonizing isolates (12 serotype VI/ST1, one serotype VI/ST19, one serotype VI/ST6, and two serotype 3/ST19)] were analyzed for presence of T7SS genes and genes encoding WXG100 proteins. We also perform bioinformatic analysis. Galleria mellonella larvae were used to compare virulence between colonizing, EOD, and mutant EOD isolates. The EOD isolate number 118659 (III/ST17) was used for knocking out the essC gene encoding a membrane-bound ATPase, considered the driver of T7SS.ResultsMost GBS T7SS loci encoded core component genes: essC, membrane-embedded proteins (essA; essB), modulators of T7SS activity (esaA; esaB; esaC) and effectors: [esxA (SAG1039); esxB (SAG1030)].Bioinformatic analysis indicated that based on sequence type (ST) the clinicalGBS isolates encode at least three distinct subtypes of T7SS machinery. In all ST1isolates we identified two copies of esxA gene (encoding putative WXG100proteins), when only 23.5% of the ST17 isolates harbored the esxA gene. Five ST17isolates encoded two copies of the essC gene. Orphaned WXG100 molecule(SAG0230), distinct from T7SS locus, were found in all tested strains, except inST17 strains where the locus was found in only 23.5% of the isolates. In ST6 andST19 isolates most of the structure T7SS genes were missing. EOD isolates demonstrated enhanced virulence in G. mellonella modelcompared to colonizing isolates. The 118659DessC strain was attenuated in itskilling ability, and the larvae were more effective in eradicating 118659DessC.ConclusionsWe demonstrated that T7SS plays a role during infection. Knocking out the essC gene, considered the driver of T7SS, decreased the virulence of ST17 responsible for EOD, causing them to be less virulent comparable to the virulence observed in colonizing isolates

Invasive Group A Streptococcal Infections, Israel

We conducted a prospective, nationwide, population-based study of invasive group A streptococcal infections in Israel. We identified 409 patients (median age 27 years; range <1-92), for an annual incidence of 3.7/100,000 (11/100,000 in Jerusalem). The mortality rate was 5%. Bacteremia occurred in 125 cases (31%). The most common illnesses were soft-tissue infection (63%) and primary bacteremia (14%). Thirty percent of patients had no identifiable risk factors for infection. Eighty-seven percent of pharyngeal carriers had the same serotype as the index patient. M types included M3 (25%), M28 (10%), and M-nontypable (33%). A marked paucity of M1 serotype (1.2%) was detected. The results highlighted concentrated pockets of invasive disease in the Jewish orthodox community (annual incidence 16/100,000)

LL-37-mediated activation of host receptors is critical for defense against group A streptococcal infection

10.1016/j.celrep.2021.108766Cell Reports34910876