The RD2 Pathogenicity Island Modifies the Disease Potential of the Group A Streptococcus

Abstract

Serotype M28 isolates of the group A Streptococcus (GAS; Streptococcus pyogenes) are non-randomly associated with cases of puerperal sepsis, a potentially life-threatening infection that can occur in women following childbirth. Previously, we discovered that the 36.3 kb RD2 pathogenicity island, which is present in serotype M28 isolates but lacking from most other isolates, promotes the ability of M28 GAS to colonize the female reproductive tract. Here, we performed a gain-of-function study in which we introduced RD2 into representative serotype M1, M49, and M59 isolates and assessed the phenotypic consequences of RD2 acquisition. All RD2-containing derivatives colonized a higher percentage of mice, and at higher colony-forming-unit levels, than did the parental isolates in a mouse vaginal colonization model. However, for two additional phenotypes, survival in heparinized whole human blood and adherence to two human vaginal epithelial cell lines, there were serotype-specific differences to RD2-acquisition. Using transcriptomic comparisons, we identified that such differences may be a consequence of RD2 altering the abundance of transcripts from select core genome genes along serotype-specific lines. Our study is the first that interrogates RD2 function in GAS serotypes other than M28 isolates, shedding light on variability in the phenotypic consequences of RD2 acquisition, and informing on why this mobile genetic element is not ubiquitous in the GAS population.

Identification of a novel CG307 sub-clade in third-generation-cephalosporin-resistant Klebsiella pneumoniae causing invasive infections in the USA

“…We identified two major events distinguishing the global CG307 cluster 1 and cluster 2 isolates. The cluster 1 strains contained a prophage that did not display any clear virulence factors, although numerous ORFs encoded proteins of unknown function and acquisition of exogenous DNA has been shown to influence the transcriptome of distant genes, possibly through the presence of transcriptional regulators in the acquired DNA [70,71]. Additionally, relative to cluster 1, cluster 2 strains had a distinct set of effector/immunity proteins from a T6SS (Fig.…”

Identification of A Novel CG307 Sub-clade in Third Generation Cephalosporin ResistantKlebsiella pneumoniaeCausing Invasive Infections in the United States

“…We identified two major events distinguishing the Global CG307 cluster 1 and cluster 2 isolates. The cluster 1 strains contained a prophage that did not contain any clear virulence factors, although numerous open reading frames encoded proteins of unknown function and acquisition of exogenous DNA has been shown to influence the transcriptome of distant genes possibly through the presence of transcriptional regulators in the acquired DNA [71, 72]. Additionally, relative to cluster 1, cluster 2 strains had a distinct set of effector/immunity proteins from a type 6 secretion system (Fig.…”

Identification of distinct impacts of CovS inactivation on the transcriptome of acapsular group A streptococci

“…However, we identified large tracts of downregulated genes in the emm28 Δ covS strain which were present in gene regions unique to emm 28, including RD2. RD2 was likely acquired from GBS, contains known and putative transcriptional regulators, and has previously been shown to alter the GAS transcriptome ( 86 ). In GBS, CovR serves to silence expression of recently acquired DNA ( 87 ), and we hypothesize that CovRS influence on RD2 expression may contribute, in part, to the magnitude of the CovS transcriptome in GAS, much of which is likely indirect in nature given the large number of contiguous genes with similar transcript patterns despite being in distinct operons.…”