Deimmunized Lysostaphin Synergizes with Small-Molecule Chemotherapies and Resensitizes Methicillin-Resistant Staphylococcus aureus to β-Lactam Antibiotics.

Autor:	Fang Y; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Kirsch JR; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Li L; The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA., Brooks SA; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Heim S; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Tan C; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Eszterhas S; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Cheng HD; Lyticon LLC, Lebanon, New Hampshire, USA., Zhao H; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Xiong YQ; The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA., Griswold KE; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA karl.e.griswold@dartmouth.edu.; Lyticon LLC, Lebanon, New Hampshire, USA.; Stealth Biologics, LLC, Lebanon, New Hampshire, USA.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2021 Feb 17; Vol. 65 (3). Date of Electronic Publication: 2021 Feb 17 (Print Publication: 2021).
DOI:	10.1128/AAC.01707-20
Abstrakt:	There is an urgent need for novel agents to treat drug-resistant bacterial infections, such as multidrug-resistant Staphylococcus aureus (MRSA). Desirable properties for new antibiotics include high potency, narrow species selectivity, low propensity to elicit new resistance phenotypes, and synergy with standard-of-care (SOC) chemotherapies. Here, we describe analysis of the antibacterial potential exhibited by F12, an innovative anti-MRSA lysin that has been genetically engineered to evade detrimental antidrug immune responses in human patients. F12 possesses high potency and rapid onset of action, it has narrow selectivity against pathogenic staphylococci, and it manifests synergy with numerous SOC antibiotics. Additionally, resistance to F12 and β-lactam antibiotics appears mutually exclusive, and, importantly, we provide evidence that F12 resensitizes normally resistant MRSA strains to β-lactams both in vitro and in vivo These results suggest that combinations of F12 and SOC antibiotics are a promising new approach to treating refractory S. aureus infections. (Copyright © 2021 American Society for Microbiology.)
Databáze:	MEDLINE
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