Abstract
Multidrug-resistant (MDR) bacteria are a major threat to public health. Bacteriophage endolysins (lysins) are a promising alternative treatment to traditional antibiotics. However, the lysins currently under development are still underestimated. Herein, we cloned the lysin from the SAP-26 bacteriophage genome. The recombinant LysSAP26 protein inhibited the growth of carbapenem-resistant Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, oxacillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium with minimum inhibitory concentrations of 5~80 µg/mL. In animal experiments, mice infected with A. baumannii were protected by LysSAP26, with a 40% survival rate. Transmission electron microscopy analysis confirmed that LysSAP26 treatment resulted in the destruction of bacterial cell walls. LysSAP26 is a new endolysin that can be applied to treat MDR A. baumannii, E. faecium, S. aureus, K. pneumoniae, P. aeruginosa, and E. coli infections, targeting both Gram-positive and Gram-negative bacteria.
Highlights
Since the introduction of penicillin, many antimicrobial drugs have been developed and widely used against pathogens, but bacteria have rapidly developed resistance to drugs [1]
The LysSAP26 protein is encoded by the 26th open reading frame of the SAP26 phage and consists of 251 amino acids (AAs; 29.1 kDa)
The protein BLAST search results showed that the LysSAP26 aligns with the N-acetylmuramoyl-L-alanine amidase, autolysin, and cysteine, the histidine-dependent amidohydrolase/peptidase (CHAP) domain-containing protein of S. aureus (E-value: 0.0)
Summary
Since the introduction of penicillin, many antimicrobial drugs have been developed and widely used against pathogens, but bacteria have rapidly developed resistance to drugs [1]. Endolysin (lysin) has emerged as a promising lead for development as a next-generation antibiotic [3,4]. Lysin has several advantages over traditional antibacterial drugs: (1) it has a completely different mechanism of action to conventional antibiotics, (2) it is expected to be advantageous in terms of safety as it has a very high selectivity for bacteria [5], (3) lysin acts on bacteria in the state of biofilm formation [6], and (4) it is expected to have a low probability of developing resistant bacteria due to its high rate of action [7]
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