Computational prediction of a phage cocktail active against multidrug-resistant bacteria

Abstract

Background Antibiotic misuse and overuse have contributed to the emergence of multi-drug resistant (MDR) bacteria, posing a serious public health problem across the globe. Phage cocktails, which combine multiple phages, provide an efficient method to combat multidrug-resistant bacterial infections. This study integrated a computational pipeline to design a phage cocktail against the bacterial strains Acinetobacter baumannii AB0057, Klebsiella pneumoniae subsp. pneumoniae HS11286, and Pseudomonas aeruginosa UCBPP-PA14. Methods The whole genome sequences of selected multidrug-resistant bacteria were accessed. Prophage sequences were identified from them which could be expressed to produce viable lytic phages against MDR bacterial strains, thereby reducing the severity of infection. Prophages were annotated for open reading frames (ORFs), putative promoters, virulence factors, transcriptional terminators, ribosomal RNAs, and transfer RNAs. A dot plot was also generated to investigate similar phages and phylogenetic analysis was performed. Results A total of 11 prophages were predicted from the bacterial genomes. About 472 open reading frames were predicted along with 3 transfer RNAs. Additionally, the presence of 754 putative promoters and 281 transcription terminator sequences was also detected. Comparative genomic and phylogenetic analyses provided insight into the diversity, relatedness, and lytic potential of the phages. The final designed phage cocktail consisted of five selected prophages including Acinetobacter baumannii prophages (2759376-2809756) and (3311844-3364667), and Klebsiella pneumoniae prophages (1288317-1338719), (1778306-1808606), and (2280703-2325555). Conclusion The phage cocktail designed in this study might be useful against MDR Acinetobacter baumannii and Klebsiella pneumoniae infections, especially where conventional antibiotics fail. Sequence similarity analysis suggested that the phage cocktail may also be effective against other carbapenemase-producing K. pneumoniae strains.