Identification and Characterization of Serotype-Specific Variation in Group A Streptococcus Pilus Expression

Abstract

Isolates of a given bacterial pathogen often display phenotypic variation, and this can negatively impact public health, for example, by reducing the efficacy of preventative measures. Here, we identify that the human pathogen group A (GAS;) expresses pili on its cell surface in a serotype-specific manner. Specifically, we show that serotype M3 GAS isolates, which are nonrandomly associated with causing particularly severe and lethal invasive infections, produce negligible amounts of pili relative to serotype M1 and M49 isolates. Performance of an interserotype transcriptome comparison (serotype M1 versus serotype M3) was instrumental in this discovery. We also identified that the transcriptional regulator Nra positively regulates pilus expression in M3 GAS isolates and that the low level of pilus expression of these isolates correlates with a low level of transcription. Finally, we discovered that the phenotypic consequences of low levels of pilus expression by M3 GAS isolates are a reduced ability to adhere to host cells and an increased ability to survive and proliferate in human blood. We propose that an enhanced ability to survive in human blood, in part due to reduced pilus expression, is a contributing factor in the association of serotype M3 isolates with highly invasive infections. In conclusion, our data show that GAS isolates express pili in a serotype-dependent manner and may inform vaccine development, given that pilus proteins are being discussed as possible GAS vaccine antigens.

Thermosensitive pilus production by FCT type 3 Streptococcus pyogenes controlled by Nra regulator translational efficiency

“…Of the nine FCT type strains, nra distribution is restricted to types 3 and 8. In addition, a point‐nonsense mutation in the Nra W218‐coding codon of M3 and M49 strains has been reported in a serotype M18 strain (Nakata et al , ; Calfee et al , ). Therefore, we postulated that Nra is involved in the thermoregulation process and performed related examinations.…”

Hypervirulent group A Streptococcus emergence in an acaspular background is associated with marked remodeling of the bacterial cell surface

“…The higher rate of near-mortality observed in mice infected with strain M4-LC-1 despite the absence of capsule is likely due to the large number of virulence factor encoding genes whose transcript levels were increased including emm , prtS , scpA , and slo . Additionally, the upregulation of genes from the FCT locus presumably would result in increased pilus production, but pilus production can either increase or decrease GAS virulence depending on strain and infection site [66–68]. It is unclear, however, how CovS inactivation affects dissemination in M4 strains as blood and organs were not collected for bacterial cell counts following IP inoculation.…”

RocA Has Serotype-Specific Gene Regulatory and Pathogenesis Activities in Serotype M28 Group A Streptococcus

“…Selected virulence factor genes with increased transcript levels in the isogenic ΔrocA mutant strain include nga (encoding NAD ϩ -glycohydrolase [ (80). Selected virulence factor genes with decreased transcript levels in the isogenic ΔrocA strain include M28_Spy0109 (encoding pilin protein) (50,81), the sag operon (carrying streptolysin S biosynthesis genes) (82), grab (encoding protein-Grelated ␣ 2 -macroglobulin binding protein) (83), ska (encoding streptokinase [SKA]) (84), and speB (encoding streptococcal cysteine protease B) (85).…”