Endovascular infections caused by methicillin-resistant Staphylococcus aureus are linked to clonal complex-specific alterations in binding and invasion domains of fibronectin-binding protein A as well as the occurrence of fnbB.

Abstract

Endovascular infections caused by Staphylococcus aureus involve interactions with fibronectin present as extracellular matrix or surface ligand on host cells. We examined the expression, structure, and binding activity of the two major S. aureus fibronectin-binding proteins (FnBPA, FnBPB) in 10 distinct, methicillin-resistant clinical isolates from patients with either persistent or resolving bacteremia. The persistent bacteremia isolates (n = 5) formed significantly stronger bonds with immobilized fibronectin as determined by dynamic binding measurements performed with atomic force microscopy. Several notable differences were also observed when the results were grouped by clonal complex 5 (CC5) strains (n = 5) versus CC45 strains (n = 5). Fibronectin-binding receptors on CC5 formed stronger bonds with immobilized fibronectin (P < 0.001). The fnbA gene was expressed at higher levels in CC45, whereas fnbB was found in only CC5 isolates. The fnbB gene was not sequenced because all CC45 isolates lacked this gene. Instead, comparisons were made for fnbA, which was present in all 10 isolates. Sequencing of fnbA revealed discrete differences within high-affinity, fibronectin-binding repeats (FnBRs) of FnBPA that included (i) 5-amino-acid polymorphisms in FnBR-9, FnBR-10, and FnBR-11 involving charged or polar side chains, (ii) an extra, 38-amino-acid repeat inserted between FnBR-9 and FnBR-10 exclusively seen in CC45 isolates, and (iii) CC5 isolates had the SVDFEED epitope in FnBR-11 (a sequence shown to be essential for fibronectin binding), while this sequence was replaced in all CC45 isolates with GIDFVED (a motif known to favor host cell invasion at the cost of reduced fibronectin binding). These complementary sequence and binding data suggest that differences in fnbA and fnbB, particularly polymorphisms and duplications in FnBPA, give S. aureus two distinct advantages in human endovascular infections: (i) FnBPs similar to that of CC5 enhance ligand binding and foster initiation of disease, and (ii) CC45-like FnBPs promote cell invasion, a key attribute in persistent endovascular infections.

• Authors: Yan Q Xiong, Batu K Sharma-Kuinkel, Nadia N Casillas-Ituarte, Vance G Fowler Jr, Thomas Rude, Alex C DiBartola, Roberto D Lins, Wessam Abdel-Hady, Steven K Lower, Arnold S Bayer
• Journal: Infection and immunity (Infect Immun) Vol. 83 Issue 12 Pg. 4772-80 (Dec 2015) ISSN: 1098-5522 [Electronic] United States
• PMID: 26416903 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Adhesins, Bacterial
• Fibronectins
• Immobilized Proteins
• Protein Isoforms
• fibronectin-binding proteins, bacterial

Topics

• Adhesins, Bacterial (chemistry, genetics, metabolism)
• Amino Acid Sequence
• Bacteremia (microbiology, pathology)
• Binding Sites
• Blood Vessels (microbiology, pathology)
• Clone Cells
• Fibronectins (chemistry, metabolism)
• Gene Expression
• Host-Pathogen Interactions
• Humans
• Immobilized Proteins (chemistry, metabolism)
• Methicillin-Resistant Staphylococcus aureus (classification, genetics, metabolism, pathogenicity)
• Molecular Sequence Data
• Polymorphism, Genetic
• Protein Binding
• Protein Isoforms (chemistry, genetics, metabolism)
• Protein Structure, Tertiary
• Staphylococcal Infections (microbiology, pathology)