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- Eradication of drug-resistant Acinetobacter baumannii by cell-penetrating peptide fused endolysin
- Jeonghyun Lim , Jaeyeon Jang , Heejoon Myung , Miryoung Song
- J. Microbiol. 2022;60(8):859-866. Published online May 25, 2022
- DOI: https://doi.org/10.1007/s12275-022-2107-y
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- 10 Web of Science
- 9 Crossref
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Abstract
- Antimicrobial agents targeting peptidoglycan have shown successful results in eliminating bacteria with high selective toxicity. Bacteriophage encoded endolysin as an alternative antibiotics is a peptidoglycan degrading enzyme with a low rate of resistance. Here, the engineered endolysin was developed to defeat multiple drug-resistant (MDR) Acinetobacter baumannii. First, putative endolysin PA90 was predicted by genome analysis of isolated Pseudomonas phage PBPA. The His-tagged PA90 was purified from BL21(DE3) pLysS and tested for the enzymatic activity using Gram-negative pathogens known for having a high antibiotic resistance rate including A. baumannii. Since the measured activity of PA90 was low, probably due to the outer membrane, cell-penetrating peptide (CPP) DS4.3 was introduced at the N-terminus of PA90 to aid access to its substrate. This engineered endolysin, DS-PA90, completely killed A. baumannii at 0.25 μM, at which concentration PA90 could only eliminate less than one log in CFU/ml. Additionally, DS-PA90 has tolerance to NaCl, where the ~50% of activity could be maintained in the presence of 150 mM NaCl, and stable activity was also observed with changes in pH or temperature. Even MDR A. baumannii strains were highly susceptible to DS-PA90 treatment: five out of nine strains were entirely killed and four strains were reduced by 3–4 log in CFU/ml. Consequently, DS-PA90 could protect waxworm from A. baumannii-induced death by ~70% for ATCC 17978 or ~44% for MDR strain 1656-2 infection. Collectively, our data suggest that CPP-fused endolysin can be an effective antibacterial agent against Gramnegative pathogens regardless of antibiotics resistance mechanisms.
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Citations
Citations to this article as recorded by
- Antimicrobial peptide thanatin fused endolysin PA90 (Tha-PA90) for the control of Acinetobacter baumannii infection in mouse model
Jeonghyun Lim, Heejoon Myung, Daejin Lim, Miryoung Song
Journal of Biomedical Science.2024;[Epub] CrossRef - Tissue damage alleviation and mucin inhibition by P5 in a respiratory infection mouse model with multidrug-resistant Acinetobacter baumannii
Jun Hee Oh, Jonggwan Park, Hee Kyoung Kang, Hee Joo Park, Yoonkyung Park
Biomedicine & Pharmacotherapy.2024; 181: 117724. CrossRef - Potential of antimicrobial peptide-fused endolysin LysC02 as therapeutics for infections and disinfectants for food contact surfaces to control Cronobacter sakazakii
Doyeon Kim, Jinwoo Kim, Minsik Kim
Food Control.2024; 157: 110190. CrossRef - Gram-negative endolysins: overcoming the outer membrane obstacle
Hazel M Sisson, Simon A Jackson, Robert D Fagerlund, Suzanne L Warring, Peter C Fineran
Current Opinion in Microbiology.2024; 78: 102433. CrossRef - LysJEP8: A promising novel endolysin for combating multidrug‐resistant Gram‐negative bacteria
Jose Vicente Carratalá, Neus Ferrer‐Miralles, Elena Garcia‐Fruitós, Anna Arís
Microbial Biotechnology.2024;[Epub] CrossRef - You get what you test for: The killing effect of phage lysins is highly dependent on buffer tonicity and ionic strength
Roberto Vázquez, Diana Gutiérrez, Zoë Dezutter, Bjorn Criel, Philippe de Groote, Yves Briers
Microbial Biotechnology.2024;[Epub] CrossRef - Endolysins: a new antimicrobial agent against antimicrobial resistance. Strategies and opportunities in overcoming the challenges of endolysins against Gram-negative bacteria
Fazal Mehmood Khan, Fazal Rasheed, Yunlan Yang, Bin Liu, Rui Zhang
Frontiers in Pharmacology.2024;[Epub] CrossRef - Characterization of Three Different Endolysins Effective against Gram-Negative Bacteria
Tae-Hwan Jeong, Hye-Won Hong, Min Soo Kim, Miryoung Song, Heejoon Myung
Viruses.2023; 15(3): 679. CrossRef - Design strategies for positively charged endolysins: Insights into Artilysin development
Jose Vicente Carratalá, Anna Arís, Elena Garcia-Fruitós, Neus Ferrer-Miralles
Biotechnology Advances.2023; 69: 108250. CrossRef
- Antimicrobial peptide thanatin fused endolysin PA90 (Tha-PA90) for the control of Acinetobacter baumannii infection in mouse model
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