Characterization of a Putative Lysin from Enterococcus Faecalis Phage IME-EFm1 and Determination of Its Protective Efficacy in Mice

Overview

Journal Curr Microbiol

Specialty Microbiology

Date 2024 Dec 2

PMID 39623033

Authors

Can Wang

Youhong Guan

Wanrong Wang

Binbin Zhang

Pulin Li

Rui Han

Wenlong Wu

Sijing Zhou

Ran Wang

Affiliations

Soon will be listed here.

Abstract

The rising tide of bacterial drug resistance has sparked renewed interest in bacteriophages, the natural predators of bacteria. Our study highlights IME-EFm1, a Caudoviricetes bacteriophage specifically targeting Enterococcus faecium. Through our investigations, we identified that the gene IME-EFm1-ORF24 encodes an amidase, referred to as gp24, with promising lytic capabilities. Remarkably, gp24 exhibited a wider lytic spectrum than its parent phage, successfully lysing 26 out of 32 E. faecium strains, compared to the phage's ability to lyse only 21. This protein demonstrated robust antibacterial activity, remaining effective at temperatures between 25 °C and 60 °C and across a pH range of 6 to 12. Additionally, gp24 displayed significant anti-biofilm properties, effectively dismantling established biofilms in vitro. In a mouse model of abdominal infection, gp24 achieved a 75% protection rate against a dose of 2 × 10 colony-forming units of E. faecium En383, significantly outperforming the control group (p < 0.05). These compelling results suggest that gp24 holds great potential as a novel antimicrobial agent for treating E. faecium infections.

References

Tian Z, Yan F, Tian X, Feng L, Cui J, Deng S . A NIR fluorescent probe for Vanin-1 and its applications in imaging, kidney injury diagnosis, and the development of inhibitor. Acta Pharm Sin B. 2022; 12(1):316-325. PMC: 8799884. DOI: 10.1016/j.apsb.2021.06.004. View

Huband M, Thompson J, Gurung N, Liu Q, Li L, Zhang J . Activity of the Novel Aminomethylcycline KBP-7072 and Comparators against 1,057 Geographically Diverse Recent Clinical Isolates from the SENTRY Surveillance Program, 2019. Antimicrob Agents Chemother. 2021; 66(1):e0139721. PMC: 8765295. DOI: 10.1128/AAC.01397-21. View

Luque-Paz D, Cuervo G, Miro J, Tattevin P . Which trial do we need? Aminopenicillin-gentamicin versus aminopenicillin-ceftriaxone for Enterococcus faecalis endocarditis. Clin Microbiol Infect. 2023; 29(6):676-678. DOI: 10.1016/j.cmi.2023.02.023. View

Tan C, Jiang L, Li W, Chan S, Baek J, Ng N . Lipid-Polymer Hybrid Nanoparticles Enhance the Potency of Ampicillin against in a Protozoa Infection Model. ACS Infect Dis. 2021; 7(6):1607-1618. PMC: 8383308. DOI: 10.1021/acsinfecdis.0c00774. View

Wang L, Zheng W, Zhong L, Yang Y, Chen Y, Hou Q . Phenylboronic Acid-Modified Gold Nanoclusters as a Nanoantibiotic to Treat Vancomycin-Resistant -Caused Infections. ACS Nano. 2023; 17(20):19685-19695. DOI: 10.1021/acsnano.3c02886. View

Prazak J, Iten M, Cameron D, Save J, Grandgirard D, Resch G . Bacteriophages Improve Outcomes in Experimental Ventilator-associated Pneumonia. Am J Respir Crit Care Med. 2019; 200(9):1126-1133. DOI: 10.1164/rccm.201812-2372OC. View

Doman J, Pandey S, Neugebauer M, An M, Davis J, Randolph P . Phage-assisted evolution and protein engineering yield compact, efficient prime editors. Cell. 2023; 186(18):3983-4002.e26. PMC: 10482982. DOI: 10.1016/j.cell.2023.07.039. View

Lee C, Kim H, Ryu S . Bacteriophage and endolysin engineering for biocontrol of food pathogens/pathogens in the food: recent advances and future trends. Crit Rev Food Sci Nutr. 2022; 63(27):8919-8938. DOI: 10.1080/10408398.2022.2059442. View

Wang Y, Wang W, Lv Y, Zheng W, Mi Z, Pei G . Characterization and complete genome sequence analysis of novel bacteriophage IME-EFm1 infecting Enterococcus faecium. J Gen Virol. 2014; 95(Pt 11):2565-2575. DOI: 10.1099/vir.0.067553-0. View

10.

Cheng M, Zhang Y, Li X, Liang J, Hu L, Gong P . Endolysin LysEF-P10 shows potential as an alternative treatment strategy for multidrug-resistant Enterococcus faecalis infections. Sci Rep. 2017; 7(1):10164. PMC: 5579260. DOI: 10.1038/s41598-017-10755-7. View

11.

Avital-Shmilovici M, Liu X, Shaler T, Lowenthal A, Bourbon P, Snider J . Mega-High-Throughput Screening Platform for the Discovery of Biologically Relevant Sequence-Defined Non-Natural Polymers. ACS Cent Sci. 2022; 8(1):86-101. PMC: 8796305. DOI: 10.1021/acscentsci.1c01041. View

12.

Gong P, Cheng M, Li X, Jiang H, Yu C, Kahaer N . Characterization of Enterococcus faecium bacteriophage IME-EFm5 and its endolysin LysEFm5. Virology. 2016; 492:11-20. DOI: 10.1016/j.virol.2016.02.006. View

13.

Nunez-Borque E, Betancor D, Pastor-Vargas C, Fernandez-Bravo S, Martin-Blazquez A, Casado-Navarro N . Personalized diagnostic approach and indirect quantification of extravasation in human anaphylaxis. Allergy. 2022; 78(1):202-213. PMC: 10087983. DOI: 10.1111/all.15443. View

14.

Linden P, Miller C . Vancomycin-resistant enterococci: the clinical effect of a common nosocomial pathogen. Diagn Microbiol Infect Dis. 1999; 33(2):113-20. DOI: 10.1016/s0732-8893(98)00148-5. View

15.

Kassa T, Chhibber S . Thermal treatment of the bacteriophage lysate of Klebsiella pneumoniae B5055 as a step for the purification of capsular depolymerase enzyme. J Virol Methods. 2011; 179(1):135-41. DOI: 10.1016/j.jviromet.2011.10.011. View

16.

Yang J, Wang P, Li C, Dong S, Song X, Zhang X . Characterization of a New M13 Metallopeptidase from Deep-Sea Shewanella sp. E525-6 and Mechanistic Insight into Its Catalysis. Front Microbiol. 2016; 6:1498. PMC: 4701951. DOI: 10.3389/fmicb.2015.01498. View

17.

Diez-Martinez R, de Paz H, Garcia-Fernandez E, Bustamante N, Euler C, Fischetti V . A novel chimeric phage lysin with high in vitro and in vivo bactericidal activity against Streptococcus pneumoniae. J Antimicrob Chemother. 2015; 70(6):1763-73. DOI: 10.1093/jac/dkv038. View

18.

Obeso J, Martinez B, Rodriguez A, Garcia P . Lytic activity of the recombinant staphylococcal bacteriophage PhiH5 endolysin active against Staphylococcus aureus in milk. Int J Food Microbiol. 2008; 128(2):212-8. DOI: 10.1016/j.ijfoodmicro.2008.08.010. View

19.

Yang M, Du C, Gong P, Xia F, Sun C, Feng X . Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model. Res Microbiol. 2015; 166(8):633-43. DOI: 10.1016/j.resmic.2015.07.008. View

20.

Gutierrez D, Fernandez L, Rodriguez A, Garcia P . Are Phage Lytic Proteins the Secret Weapon To Kill ?. mBio. 2018; 9(1). PMC: 5784253. DOI: 10.1128/mBio.01923-17. View