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A Factor H-Fc fusion protein increases complement-mediated opsonophagocytosis and killing of community associated methicillin-resistant Staphylococcus aureus.

Authors :
Sage MAG
Cranmer KD
Semeraro ML
Ma S
Galkina EV
Tran Y
Wycoff KL
Sharp JA
Source :
PloS one [PLoS One] 2022 Mar 24; Vol. 17 (3), pp. e0265774. Date of Electronic Publication: 2022 Mar 24 (Print Publication: 2022).
Publication Year :
2022

Abstract

Staphylococcus aureus employs a multitude of immune-evasive tactics to circumvent host defenses including the complement system, a component of innate immunity central to controlling bacterial infections. With antibiotic resistance becoming increasingly common, there is a dire need for novel therapies. Previously, we have shown that S. aureus binds the complement regulator factor H (FH) via surface protein SdrE to inhibit complement. To address the need for novel therapeutics and take advantage of the FH:SdrE interaction, we examined the effect of a fusion protein comprised of the SdrE-interacting domain of FH coupled with IgG Fc on complement-mediated opsonophagocytosis and bacterial killing of community associated methicillin-resistant S. aureus. S. aureus bound significantly more FH-Fc compared to Fc-control proteins and FH-Fc competed with serum FH for S. aureus binding. FH-Fc treatment increased C3-fragment opsonization of S. aureus for both C3b and iC3b, and boosted generation of the anaphylatoxin C5a. In 5 and 10% serum, FH-Fc treatment significantly increased S. aureus killing by polymorphonuclear cells. This anti-staphylococcal effect was evident in 75% (3/4) of clinical isolates tested. This study demonstrates that FH-Fc fusion proteins have the potential to mitigate the protective effects of bound serum FH rendering S. aureus more vulnerable to the host immune system. Thus, we report the promise of virulence-factor-targeted fusion-proteins as an avenue for prospective anti-staphylococcal therapeutic development.<br />Competing Interests: The authors have declared that no competing interests exist.

Details

Language :
English
ISSN :
1932-6203
Volume :
17
Issue :
3
Database :
MEDLINE
Journal :
PloS one
Publication Type :
Academic Journal
Accession number :
35324969
Full Text :
https://doi.org/10.1371/journal.pone.0265774