Investigating Bacteriophages Targeting the Opportunistic Pathogen Acinetobacter baumannii.

Kathryn M Styles,Sophie E Smith,Rapee Thummeepak,Elizabeth M H Wellington,Andrew Millard,Gabrielle S Christie,Sutthirat Sitthisak,Udomluk Leungtongkam,Christopher G Dowson,John Moat,Antonia P Sagona

doi:10.3390/antibiotics9040200

Kathryn M Styles, Sophie E Smith + Show 9 more

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https://doi.org/10.3390/antibiotics9040200

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Abstract

The multi-drug resistance of the opportunistic pathogen Acinetobacter baumannii is of growing concern, with many clinical isolates proving to be resistant to last resort as well as front line antibiotic treatments. The use of bacteriophages is an attractive alternative to controlling and treating this emerging nosocomial pathogen. In this study, we have investigated bacteriophages collected from hospital wastewater in Thailand and we have explored their activity against clinical isolates of A. baumannii. Bacteriophage vB_AbaM_PhT2 showed 28% host range against 150 multidrug resistant (MDR) isolates and whole genome sequencing did not detect any known virulence factors or antibiotic resistance genes. Purified vB_AbaM_PhT2 samples had endotoxin levels below those recommended for preclinical trials and were not shown to be directly cytotoxic to human cell lines in vitro. The treatment of human brain and bladder cell lines grown in the presence of A. baumannii with this bacteriophage released significantly less lactate dehydrogenase compared to samples with no bacteriophage treatment, indicating that vB_AbaM_PhT2 can protect from A. baumannii induced cellular damage. Our results have also indicated that there is synergy between this bacteriophage and the end line antibiotic colistin. We therefore propose bacteriophage vB_AbaM_PhT2 as a good candidate for future research and for its potential development into a surface antimicrobial for use in hospitals.

Highlights

Acinetobacter baumannii infection has become a research priority due to its exceptional ability to acquire antimicrobial resistance (AMR) [1,2]
When vPhT2 was applied to human cell lines that had been exposed to A. baumannii for an hour, there was a 90.98 ± 0.49% and 84.01 ± 1.74% reduction in LDH production over the 23 h by T24 there was a 90.98 ± 0.49% and 84.01 ± 1.74% reduction in LDH production over the 23 hours by and T24
Seventeen bacteriophages were isolated from wastewater at Buddhachinaraj and Bang Rakam hospitals in Phitsanulok province, Thailand in 2010 and were screened against 150 multidrug resistant (MDR) A. baumannii strains collected from five hospitals [11,22,27,29] using a spot test method as described previously [27]

Summary

Introduction

Acinetobacter baumannii infection has become a research priority due to its exceptional ability to acquire antimicrobial resistance (AMR) [1,2] Strains of this Gram negative bacterium have been shown to have high genetic diversity and large genetic ‘resistance islands’ [3], and there have been cases of pan-drug resistant isolates that are resistant to all known clinical antibiotics [4]. This has made A. baumannii a formidable pathogen in the nosocomial environment, against. There is no longer an empirical antimicrobial agent treatment [8] and the extensive use of the broad spectrum carbapenems [9] has led the World Health Organization to highlight carbapenem resistant A. baumannii as a Class 1: Priority

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