The characteristic and potential therapeutic effect of isolated multidrug-resistant Acinetobacter baumannii lytic phage

Behnam Sisakhtpour,Sharareh Moghim,Nafiseh Hosseini,Arezoo Mirzaei,Vajihe Karbasizadeh,Mehdi Shabani

doi:10.1186/s12941-022-00492-9

Behnam Sisakhtpour, Sharareh Moghim + Show 4 more

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https://doi.org/10.1186/s12941-022-00492-9

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Abstract

BackgroundWidespread misuse of antibiotics caused bacterial resistance increasingly become a serious threat. Bacteriophage therapy promises alternative treatment strategies for combatting drug-resistant bacterial infections. In this study, we isolated and characterized a novel, potent lytic bacteriophage against multi-drug resistant (MDR) Acinetobacter baumannii and described the lytic capability and endolysin activity of the phage to evaluate the potential in phage therapy.MethodsA novel phage, pIsf-AB02, was isolated from hospital sewage. The morphological analysis, its host range, growth characteristics, stability under various conditions, genomic restriction pattern were systematically investigated. The protein pattern of the phage was analyzed, and the endolysin activity of the phage was determined under the non-denaturing condition on SDS-PAGE. The optimal lytic titer of phage was assessed by co-culture of the phage with clinical MDR A. baumannii isolates. Finally, HeLa cells were used to examine the safety of the phage.ResultsThe morphological analysis revealed that the pIsf-AB02 phage displays morphology resembling the Myoviridae family. It can quickly destroy 56.3% (27/48) of clinical MDR A. baumannii isolates. This virulent phage could decrease the bacterial host cells (from 108 CFU/ml to 103 CFU/ml) in 30 min. The optimum stability of the phage was observed at 37 °C. pH 7 is the most suitable condition to maintain phage stability. The 15 kDa protein encoded by pIsf-AB02 was detected to have endolysin activity. pIsf-AB02 did not show cytotoxicity to HeLa cells, and it can save HeLa cells from A. baumannii infection.ConclusionIn this study, we isolated a novel lytic MDR A. baumannii bacteriophage, pIsf-AB02. This phage showed suitable stability at different temperatures and pHs, and demonstrated potent in vitro endolysin activity. pIsf-AB02 may be a good candidate as a therapeutic agent to control nosocomial infections caused by MDR A. baumannii.

Highlights

Widespread misuse of antibiotics caused bacterial resistance increasingly become a serious threat
Few samples had the intermediate resistance pattern, while susceptibility was not found among the multi-drug resistant (MDR) A. baumannii isolates (Fig. 2)
Most MDR A. baumannii isolates in this study were sensitive to pIsf-AB02 (27/48); it was chosen for further study

Summary

Introduction

Widespread misuse of antibiotics caused bacterial resistance increasingly become a serious threat. Bacteriophage therapy promises alternative treatment strategies for combatting drug-resistant bacterial infections. We isolated and characterized a novel, potent lytic bacteriophage against multi-drug resistant (MDR) Acinetobacter baumannii and described the lytic capability and endolysin activity of the phage to evaluate the potential in phage therapy. Acinetobacter baumannii (A. baumannii) is responsible for many health care infections, burn and wound infections [1] This non-fermentative, non-motile, Sisakhtpour et al Ann Clin Microbiol Antimicrob (2022) 21:1 to most known antibiotics [4, 5]. Bacteriophage therapy is a promising alternative treatment for MDR bacterial infections. The isolation and characterization of lytic phages is a potential strategy for fighting Multi-Drug Resistance (MDR) A. baumannii [11, 14]. Potential therapeutic phages must be thoroughly examined for safety and effectiveness [15, 16]

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