The R28 protein of Streptococcus pyogenes is related to several group B streptococcal surface proteins, confers protective immunity and promotes binding to human epithelial cells

Abstract

SummaryThe R28 protein is a surface molecule expressed by some strains of Streptococcus pyogenes (group A streptococcus). Here, we present evidence that R28 may play an important role in virulence. Sequence analysis demonstrated that R28 has an extremely repetitive sequence and can be viewed as a chimera derived from the three surface proteins Rib, a and b of the group B streptococcus (GBS). Thus, the gene encoding R28 may have originated in GBS. The R28 protein promotes adhesion to human epithelial cells, as shown by experiments with an R28-negative mutant and by the demonstration that antibodies to highly puri®ed R28 inhibited adhesion. In a mouse model of lethal intraperitoneal S. pyogenes infection, antibodies to R28 conferred protective immunity. However, the virulence of an R28-negative mutant was similar to that of the parental strain in the intraperitoneal infection model. Together, these data indicate that R28 represents a novel type of adhesin expressed by S. pyogenes and that R28 may also act as a target for protective antibodies at later stages of an infection. We consider the hypothesis that R28 played a pathogenetic role in the well-known epidemics of childbed fever (puerperal fever), which were caused by S. pyogenes. A role for R28 in these epidemics is suggested by epidemiological data.

Host–pathogen interactions in Streptococcus pyogenes infections, with special reference to puerperal fever and a comment on vaccine development

“…Virtually nothing is known about molecular mechanisms in puerperal fever, but an epidemiological study in Britain showed that the surface protein R28 was common among S. pyogenes strains isolated from recent outbreaks of puerperal fever, but was found in only a minority of pharyngitis strains [23]. This over-representation of R28-expressing strains among puerperal fever isolates led us to hypothesize that the R28 protein played an important role in the epidemics of puerperal fever [24]. For obvious reasons, S. pyogenes isolates from the 18 th and 19 th century epidemics of puerperal fever were not available for characterization, but analysis of cases of puerperal fever reported in the litterature in which the S. pyogenes strains were serotyped supported the hypothesis that R28-expressing strains were overrepresented also among puerperal fever isolates recovered earlier in the 20 th century [24].…”

“…This over-representation of R28-expressing strains among puerperal fever isolates led us to hypothesize that the R28 protein played an important role in the epidemics of puerperal fever [24]. For obvious reasons, S. pyogenes isolates from the 18 th and 19 th century epidemics of puerperal fever were not available for characterization, but analysis of cases of puerperal fever reported in the litterature in which the S. pyogenes strains were serotyped supported the hypothesis that R28-expressing strains were overrepresented also among puerperal fever isolates recovered earlier in the 20 th century [24]. Although many S. pyogenes strains isolated from 20 th century cases of puerperal fever probably did not express R28, this finding does not contradict the hypothesis that R28 may favor the emergence of epidemics, because endemic isolates, that cause sporadic cases or small outbreaks, would be expected to be non-clonal, while only epidemic strains would be expected to be clonal [25].…”

“…Molecular characterization of the R28 protein [24] showed that it is a member of a family of extremely repetitive surface proteins first identified in the group B streptococcus (GBS; Streptococcus agalactiae) [26], which is often found in the normal vaginal flora and causes serious invasive disease in newborns [27]. The protein family that includes R28 was first defined by the GBS proteins Rib and α [26,28,29] and among these GBS proteins R28 is most closely related to Rib (Fig.…”

“…2). Indeed, R28 can be viewed as a chimera derived from Rib and two other GBS surface proteins [24].…”

“…Interestingly, the R28 protein promotes binding of S. pyogenes to a human epithelial cell line of cervical origin [24], and one can speculate that the Rib protein of GBS has similar function, allowing GBS to colonize the human genital tract. However, attempts to demonstrate that Rib is an adhesin have been unsuccessful so far.…”