Re-sensitising XDR biofilms using a combination of bacteriophage cocktails and colistin: a natural approach

Devanga Ragupathi, N. K.; Muthuirulandi Sethuvel, D. P.; Gopikrishnan, M.; Murugan, D.; Juliet, R.; Majhi, M.; Murugesan, M.; C, G. P. D.; Wannigama, L.; Monk, P. N.; Karunakaran, E.; Veeraraghavan, B.

doi:10.1101/2022.02.04.479063

bioRxiv · 10.1101/2022.02.04.479063

Re-sensitising XDR biofilms using a combination of bacteriophage cocktails and colistin: a natural approach

Devanga Ragupathi, N. K.·Muthuirulandi Sethuvel, D. P.·Gopikrishnan, M.·Murugan, D.·Juliet, R.·Majhi, M.·Murugesan, M.·C, G. P. D.·Wannigama, L.·Monk, P. N.·Karunakaran, E.·Veeraraghavan, B.

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Abstract

Persistent antibiotic use results in the rise of antimicrobial resistance with limited or no choice for multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria. This necessitates a need for alternative therapy to effectively combat clinical pathogens that are resistant to last resort antibiotics. The study investigates hospital sewage as a potential source of bacteriophages to control MDR/XDR bacterial pathogens. 81 samples were screened for phages against selected clinical pathogens. 10 phages were isolated against A. baumannii, 5 phages against K. pneumoniae and 16 phages obtained against P. aeruginosa. The novel phages were observed to be strain-specific with a complete growth inhibition of up to 6 hrs. Phage plus colistin combinations further reduced the MBEC of colistin up to 16 folds. Notably, cocktail of phages exhibited supreme efficacy with complete killing at 0.5-1 {micro}g/ml colistin concentrations. Thus, phages specific to clinical strains has a higher edge in treating nosocomial pathogens with their proven anti-biofilm efficacy. In addition, analysis of phage genomes revealed close phylogenetic relations with phages reported from Europe, China and other neighbouring countries. This study serves as a reference and can be extended to other antibiotics and phage types to assess optimum synergistic combinations to combat various drug resistant pathogens in the ongoing AMR crisis.

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Devanga Ragupathi, N. K., Muthuirulandi Sethuvel, D. P., Gopikrishnan, M., Murugan, D., Juliet, R., Majhi, M., Murugesan, M., C, G. P. D., Wannigama, L., Monk, P. N., Karunakaran, E., Veeraraghavan, B.. 2022-02-04. Re-sensitising XDR biofilms using a combination of bacteriophage cocktails and colistin: a natural approach. https://doi.org/10.1101/2022.02.04.479063

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