Fba, a novel fibronectin‐binding protein from Streptococcus pyogenes, promotes bacterial entry into epithelial cells, and the fba gene is positively transcribed under the Mga regulator

Abstract

In infection by Streptococcus pyogenes, fibronectin (Fn)‐binding proteins play important roles as adhesins and invasins. Here, we present a novel Fn‐binding protein of S. pyogenes that exhibits a low similarity to other Fn‐binding proteins reported. After searching the Oklahoma Streptococcal Genome Sequencing Database for open reading frames (ORFs) with an LPXTG motif, nine ORFs were found among those recognized as putative surface proteins, and one of them was designated as Fba. The fba gene was found in M types 1, 2, 4, 22, 28 and 49 of S. pyogenes, but not in other serotypes or groups of streptococci. Fba, a 37.8 kDa protein, possesses three or four proline‐rich repeat domains and exhibits a high homology to FnBPA, the Fn‐binding protein of Staphylococcus aureus. Recombinant Fba exhibited a strong binding ability to Fn. In addition, Fba‐deficient mutants showed diminished invasive capabilities to HEp‐2 cells and low mortality in mice following skin infection. The fba gene was located downstream of the mga regulon and analysis using an mga‐inactivated mutant revealed that it was transcribed under the control of the Mga regulator. These results indicate that Fba is a novel protein and one of the important virulence factors of S. pyogenes.

Similar Ability of FbaA with M Protein to Elicit Protective Immunity Against Group A Streptococcus Challenge in Mice

“…FbaA distributes broadly among streptococcal species, such as M1, 2, 4, 9, 13, 22, 28, etc. Moreover, it exhibits a high homology in different types of S. pyogenes (6). Recently, Terao et al reported that the immunogenic domains of FbaA were N terminus and PRR domain (10), and our recent data (not shown) showed the strongest immunogenic domain of FbaA was coiled-coil domain (CC) of the N terminus.…”

“…Unfortunately, M protein is restricted as a vaccine candidate because it possesses multiple serotypes and often causes tissue crossreactions. A novel protein, FbaA, an Fn-binding protein expressed on the surface of GAS, was reported by Terao (6). Pandiripally et al confirmed the functions of FbaA in promoting entry of GAS into the cytoplasm of human epithelial cells through binding human complement regulatory proteins FH and factor H-like protein (FHL-1) (7).…”

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

“…Multiple in vitro studies have demonstrated that GAS isolates associated with invasive diseases efficiently invade epithelial cells (6,7). Although programmed cell death is an essential part of host defense against pathogens, it is considered that internalized GAS exploits this process to access the underlying sterile tissues (8,9).…”

A MyD88–JAK1–STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus

“…It is equipped with various surface-displayed and secreted virulence factors, such as M proteins, 31,32 Fba proteins, 33,34 C5a and SpeB, 35,36 and these proteins play a vital role in streptococcal colonization, invasion, dissemination and host damage. 37 GAS can survive and multiply in host cells, which requires suppression of host innate immunity.…”