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Subject: Biotechnology and molecular Biology × End date: 2022 × Start date: 2022 × Thesis Type: Ph.D ×
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    ThesisItemOpen Access
    Characterization of bacteriophages against ESKAPE pathogens and assessment of their synergy with antibiotics
    (Chaudhary Charan Singh Haryana Agricultural University hisar, 2022-09) Vashisth, Medhavi; Yashveer, Shikha
    The current study was carried out to isolate and characterize bacteriophages with therapeutic potential against ESKAPE pathogens and their synergy assessment with the routinely used antibiotics to control the infection caused by drug resistant strains. A total of 36 different bacteriophages were isolated and characterized for their morphology, physiological stability, molecular & proteomic profile, lytic spectrum and lytic efficiency using spot and EOP assays. Phages φSA116, φKP205, φAB182, and φPA180 were the most lytic out of all the phages isolated during this study. Further, eight bacteriophages were tested with an array of antibiotics to control the growth of drug resistant strains of ESKAPE pathogens using disk embedded double agar overlay method, time kill curve assays in liquid infection models, mutant frequency assays, and in eradication of biofilms. After preliminary screening by double agar overlay method, phages φSA115 (p<0.0001), φSA116 (p<0.0001), φKP202 (p<0.001), and φAB182 (p<0.001 & p<0.0001), showed synergy with sub-inhibitory concentrations of β-lactams (CEP, CAZ, CTX) and polymyxins (PB, CL) to inhibit the bacterial growth as observed by reduced bacterial turbidity compared to the individual treatment with phages and antibiotics. The synergistic effect of phages φKP205 (p<0.0001), φPA176 (p<0.0001), and φPA180 (p<0.0001) with β-lactams (AT, CAZ and PI) was even more pronounced in terms of greater reduction in bacterial turbidity. However, with some of the antibiotics (AK, GEN, AZM, TE), antagonistic activity, in form of smaller sized plaques of bacteriophages was observed. The combination of φPA180 with AT and PI demonstrated the strongest suppression of resistance evolution. A cocktail of φAB182, φKP205, and φPA180 phages, with colistin was demonstrated to successfully eradicate multi-species biofilms of ESKAPE pathogens. Thus, combination therapy of phages with antibiotics presents a potential alternative to control difficult-to-treat infections caused by resistant strains of ESKAPE pathogens.