The MiiA motif is a common marker present in polytopic surface proteins of oral and urinary tract invasive bacteria.
Many surface virulence factors of bacterial pathogens show mosaicism and confounding phylogenetic origin. The Streptococcus gordonii platelet-binding GspB protein, the Streptococcus sanguinis SrpA adhesin and the Streptococcus pneumoniae DiiA protein, share an imperfect 27-residue motif. Given the disparate domain architectures of these proteins and its association to invasive disease, this motif was named MiiA from Multiarchitecture invasion-involved motif A. MiiA is predicted to adopt a beta-sheet folding, probably related to the Ig-like fold, with a symmetrical positioning of two conserved aspartic residues. A specific hidden Markov model profiling MiiA was built, which specifically detected the motif in proteins from 58 species, mainly in cell-wall proteins from Gram-positive bacteria. These proteins contained one to ten MiiA motifs, which were embedded within larger repeat units of 70-82 residues. MiiA motifs combined to other domains and elements such as coiled-coils and low-complexity regions. The species carrying MiiA-proteins included commensals from the urogenital tract and the oral cavity, which can cause opportunistic endocarditis and sepsis. Intra-protein MiiA repeats showed a complex mixture of orthologal, paralogal and inter-species relationships, suggestive of a multistep origin. Presence of these repeats in proteins involved in oligosaccharide recognition and lifestyle of species suggest a putative function for MiiA repeats in sugars binding, probably those present in receptors of epithelial and blood cells. MiiA modules appear to have been transferred horizontally between species co-habiting in the same niche to create their own MiiA-containing determinants. The present work provides a global study and a catalog of potential MiiA virulence factors that should be analyzed experimentally.
Instituto de Salud Carlos III, Centro Nacional de Microbiología, Carretera a Pozuelo, km 2.2, Majadahonda, 28220 Madrid, Spain. Electronic address: mgaliano@isciii.es.
Antonio J
AJ
Martín-Galiano
D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D017124:Conserved Sequence; D015870:Gene Expression; D006801:Humans; D008390:Markov Chains; D009059:Mouth Diseases / Q000382:microbiology; D010802:Phylogeny; D054773:Streptococcus gordonii / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D013298:Streptococcus sanguis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D014552:Urinary Tract Infections / Q000382:microbiology
D001426:Bacterial Proteins; C501626:serine-rich glycoprotein A, Streptococcus sanguis
Hidden Markov model; Invasive disease; Lectin; Modular domain; Viridans streptococci; Virulence factor