title: Impact of the SpeB protease on binding of the complement regulatory proteins factor H and factor H-like protein 1 by Streptococcus pyogenes.
abstract: Microbial pathogens often exploit human complement regulatory proteins such as factor H (FH) and factor H-like protein 1 (FHL-1) for immune evasion. Fba is an FH and FHL-1 binding protein expressed on the surface of the human pathogenic bacterium Streptococcus pyogenes, a common agent of pharyngeal, skin, and soft-tissue infections. Fba has been shown to contribute to phagocytosis resistance, intracellular invasion, and virulence in mice. Here, we look at the role of Fba in recruitment of FH and FHL-1 by five serotype M1 isolates of streptococci. Inactivation of fba greatly inhibited binding of FH and FHL-1 by all isolates, indicating that Fba is a major FH and FHL-1 binding factor of serotype M1 streptococci. For three isolates, FH binding was significantly reduced in stationary-phase cultures and correlated with high levels of protease activity and SpeB (an extracellular cysteine protease) protein in culture supernatants. Analysis of a speB mutant confirmed that SpeB accounts for the loss of Fba from the cell surface, suggesting that the protease may modulate FH and FHL-1 recruitment during infection. Comparisons of fba DNA sequences revealed that the FH and FHL-1 binding site in Fba is conserved among the M1 isolates. Although the ligand binding site is not strictly conserved in Fba from a serotype M49 isolate, the M49 Fba protein was found to bind both FH and FHL-1. Collectively, these data indicate that binding of FH and FHL-1 is a conserved function of Fba while modulation of Fba function by SpeB is variable.
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, Mail Stop 3029, The University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wei
authors.forename: Vinod
authors.initials: V
authors.lastname: Pandiripally
authors.forename: Eugene
authors.initials: E
authors.lastname: Gregory
authors.forename: Micaya
authors.initials: M
authors.lastname: Clymer
authors.forename: David
authors.initials: D
authors.lastname: Cue
mesh_terms: D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000378:metabolism*; D005098:Exotoxins / Q000502:physiology*; D005634:Fructose-Bisphosphate Aldolase; D006801:Humans; D008969:Molecular Sequence Data; D013297:Streptococcus pyogenes / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; D002352:Carrier Proteins; D003180:Complement C3b Inactivator Proteins; D005098:Exotoxins; C445329:Fba protein, Streptococcus pyogenes; C027951:erythrogenic toxin; D017242:Complement Factor H; D005634:Fructose-Bisphosphate Aldolase