Protein PAB, an Albumin-binding Bacterial Surface Protein Promoting Growth and Virulence

Abstract

The anaerobic bacterium Peptostreptococcus magnus is a human commensal and pathogen. Previous work has shown that strains of P. magnus isolated from patients with gynecological disease (vaginosis) frequently express an immunoglobulin (Ig) light chain-binding protein called protein L. Here we report that strains isolated from localized suppurative infections bind human serum albumin (HSA), whereas commensal isolates bind neither Ig nor HSA. The HSA-binding protein PAB was extracted from the bacterial surface or isolated from the culture supernatant of the P. magnus strain ALB8. Protein PAB was shown to have two homologous HSA-binding domains, GA and uGA. GA is absent in the sequence of a related protein from another P. magnus strain and shows a high degree of homology to the HSA-binding domains of streptococcal protein G. Therefore GA is believed to have recently been shuffled as a module from genes of other bacterial species into the protein PAB gene. This GA module was shown to exhibit a much higher affinity for HSA than uGA and was also found to be present in all of the isolates tested from localized suppurative infections, indicating a role in virulence. Moreover, when peptostreptococci or streptococci expressing the GA module were grown in the presence of HSA, the growth rate was substantially increased. Thus, the HSA binding activity of the GA module adds selective advantages to the bacteria, which increases their virulence in the case of P. magnus strains.

The design and characterization of two proteins with 88% sequence identity but different structure and function

“…Protein G contains two types of domains that bind to serum proteins in blood: G A domains of 47 structured amino acids that bind to HSA (2, 3) and G B domains of 56 structured amino acids that bind to the constant (Fc) region of IgG (4,5). The ability to bind serum proteins apparently confers selective advantage to pathogenic bacteria by allowing them to camouflage themselves with host proteins (6).…”

Albumin, in the Presence of Calcium, Elicits a Massive Increase in Extracellular Bordetella Adenylate Cyclase Toxin

“…Previous studies have identified that albumin influences the growth and virulence of microorganisms (64)(65)(66)(67). Specifically, albumin has been shown to bind to the bacterial surface of group B streptococci and inactivate the antibacterial peptide CXCL9, increase expression of virulence genes in Pseudomonas aeruginosa, and specifically induce natural competence in Acinetobacter baumannii (65)(66)(67).…”

Binding of Albumin Promotes Bacterial Survival at the Epithelial Surface

“…So-called exon or module shuffling resulting in functional hybrid proteins has played a major role in the evolution of eukaryotic genes, and in this process, introns have been crucial by increasing the probability of favorable duplication and recombination events (44,45). The known cases of module shuffling took place millions of years ago, and there were no contemporary examples (46) until the discovery of PAB revealed that this protein is the product of a transfer of the GA module from the protein G gene of GGS to the PAB gene of F. magna and that the conjugative plasmid pCF10 from Enterococcus faecalis participated in the transfer and recombination events resulting in the mosaic organization of PAB (22). The high degree of homology between the GA modules of proteins G and PAB and the short generation times in bacteria suggested that the shuffling of GA had occurred recently.…”

“…The HSA-binding GA module (repeats of 45 amino acid residues each) was originally discovered in protein G (19,20) but was given its name (GA stands for protein G-related albumin-binding module) when homologous modules were identified in an HSA-binding protein of F. magna (formerly Peptostreptococcus magnus) called PAB (22). F. magna is an anaerobic Gram-positive coccus found in the normal human bacterial flora at all non-sterile body surfaces, including the skin and oropharynx, and analogous to GGS, F. magna is also an opportunistic pathogen (Ref.…”

“…The interactions with HSA and IgG occur independently, and the organization of protein G allows GGS to coat their surface with an inner layer of IgG and an outer layer of HSA, the two most abundant proteins of human plasma. Surface proteins containing HSA-binding GA modules are also present in strains of the anaerobic bacterium Finegoldia magna (22) and in a biofilm-generating protein (Embp) of Staphylococcus epidermidis (25,26). The bacterial species that express proteins containing GA modules are all part of the normal human bacterial flora.…”