Lysin LysMK34 of Bacteriophage PMK34 Has a Turgor Pressure-Dependent Intrinsic Antibacterial Activity and Reverts Colistin Resistance.
Karim Abdelkader, Diana Gutiérrez, Dennis Grimon, Patricia Ruas-Madiedo, Cédric Lood, Rob Lavigne, Amal Safaan, Ahmed S Khairalla, Yasser Gaber, Tarek Dishisha, Yves Briers
Author Information
Karim Abdelkader: Department of Biotechnology, Ghent University, Ghent, Belgium. ORCID
Diana Gutiérrez: Department of Biotechnology, Ghent University, Ghent, Belgium. ORCID
Dennis Grimon: Department of Biotechnology, Ghent University, Ghent, Belgium.
Patricia Ruas-Madiedo: Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Villaviciosa, Asturias, Spain. ORCID
Cédric Lood: Department of Biosystems, KU Leuven, Leuven, Belgium. ORCID
Rob Lavigne: Department of Biosystems, KU Leuven, Leuven, Belgium. ORCID
Amal Safaan: Department of Microbiology and Immunology, Faculty of Pharmacy, Menoufia University, Shebin ElKoum, Egypt.
Ahmed S Khairalla: Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. ORCID
Yasser Gaber: Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. ORCID
Tarek Dishisha: Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. ORCID
Yves Briers: Department of Biotechnology, Ghent University, Ghent, Belgium yves.briers@ugent.be. ORCID
The prevalence of extensively and pandrug-resistant strains of leaves little or no therapeutic options for treatment for this bacterial pathogen. Bacteriophages and their lysins represent attractive alternative antibacterial strategies in this regard. We used the extensively drug-resistant strain MK34 to isolate the bacteriophage PMK34 (vB_AbaP_PMK34). This phage shows fast adsorption and lacks virulence genes; nonetheless, its narrow host spectrum based on capsule recognition limits broad application. PMK34 is a member of the and has a 41.8-kb genome (50 open reading frames), encoding an endolysin (LysMK34) with potent muralytic activity (1,499.9 ± 131 U/μM), a typical mesophilic thermal stability up to 55°C, and a broad pH activity range (4 to 10). LysMK34 has an intrinsic antibacterial activity up to 4.8 and 2.4 log units for and strains, respectively, but only when a high turgor pressure is present. The addition of 0.5 mM EDTA or application of an osmotic shock after treatment can compensate for the lack of a high turgor pressure. The combination of LysMK34 and colistin results in up to 32-fold reduction of the MIC of colistin, and colistin-resistant strains are resensitized in both Mueller-Hinton broth and 50% human serum. As such, LysMK34 may be used to safeguard the applicability of colistin as a last-resort antibiotic. is one of the most challenging pathogens for which development of new and effective antimicrobials is urgently needed. Colistin is a last-resort antibiotic, and even colistin-resistant strains exist. Here, we present a lysin that sensitizes for colistin and can revert colistin resistance to colistin susceptibility. The lysin also shows a strong, turgor pressure-dependent intrinsic antibacterial activity, providing new insights in the mode of action of lysins with intrinsic activity against Gram-negative bacteria.
