Bacteriophage Laboratory, National Centre for Veterinary Type Cultures, ICAR - National Research Centre on Equines, Sirsa Road, Hisar, Haryana 125001, India; Department of Molecular Biology, Biotechnology and Bioinformatics, Chaudhary Charan Singh Haryana Agricultural University, Hisar, Haryana 125004, India.
Department of Molecular Biology, Biotechnology and Bioinformatics, Chaudhary Charan Singh Haryana Agricultural University, Hisar, Haryana 125004, India.
Virus Res. 2022 Nov;321:198909. doi: 10.1016/j.virusres.2022.198909. Epub 2022 Aug 31.
Combination therapy of bacteriophages and antibiotics requires careful selection of specific antibiotics as it is crucial towards determining the success of phage therapy to treat multiple drug-resistant bacterial infections. So, we examined how different antibiotics can affect phage lytic activity when used in combination against targeted bacteria. Various antibiotics targeting bacterial protein synthesis pathways were tested for their bactericidal action in combination with bacteriophages of Acinetobacter baumannii (φAB145, φAB182), Staphylococcus aureus (φSA115, φSA116) and Salmonella Typhimurium (φST143, φST188). The phages displayed highly significant antagonism with most of the protein/ribosomal machinery targeting antibiotics: φSA115 (13/13); φSA116 (13/13); φST143 (11/13); φAB145 (11/13); φST188 (9/13); φAB182 (7/13). To validate this antagonistic effect, synergy assessment of these phages with gentamicin (GEN) and tetracycline (TE) was performed using time kill curve assays and counting the remaining viable bacterial cells at the end of the experiment. An increase in bacterial turbidity in phage-antibiotic combination groups was observed as compared to the treatment with phages individually. Also, GEN exhibited 4.22, 5.90, 2.02, 3.15, 2.68, and 2.60 log proliferation in viable cell count, respectively, for φSA115, φSA116, φST145, φAB182, φST143 and φAB188 in combination group in comparison to their individual actions. TE supplementation also led to 2.40, 4.90, 1.61, 2.73, 3.93, and 1.81 log increments in viable bacterial count when combined with φSA115, φSA116, φST145, φAB182, φST143 and φAB188, respectively. This study concludes that antibiotics targeting the bacterial protein biosynthetic machinery may lead to a reduction in the lytic activity of bacteriophages, thus lowering their therapeutic potential. Hence, such compounds must be carefully screened before their employment in combination treatment regimens.
噬菌体与抗生素联合治疗需要仔细选择特定的抗生素，因为这对于确定噬菌体治疗多重耐药性细菌感染的成功至关重要。因此，我们研究了不同的抗生素在联合针对目标细菌时如何影响噬菌体的裂解活性。我们测试了各种针对细菌蛋白质合成途径的抗生素，以研究它们与鲍曼不动杆菌（φAB145、φAB182）、金黄色葡萄球菌（φSA115、φSA116）和鼠伤寒沙门氏菌（φST143、φST188）噬菌体联合使用时的杀菌作用。结果显示，这些噬菌体与大多数靶向抗生素的蛋白质/核糖体机制显示出高度的拮抗作用：φSA115（13/13）；φSA116（13/13）；φST143（11/13）；φAB145（11/13）；φST188（9/13）；φAB182（7/13）。为了验证这种拮抗作用，我们使用时间杀伤曲线测定和实验结束时计数剩余存活细菌细胞的方法，评估了这些噬菌体与庆大霉素（GEN）和四环素（TE）的协同作用。与单独使用噬菌体相比，噬菌体-抗生素联合组的细菌浊度增加。此外，在组合组中，GEN 分别使 φSA115、φSA116、φST145、φAB182、φST143 和 φAB188 的活菌计数分别增加了 4.22、5.90、2.02、3.15、2.68 和 2.60 个对数，而 TE 补充剂与 φSA115、φSA116、φST145、φAB182、φST143 和 φAB188 联合使用时，活菌计数分别增加了 2.40、4.90、1.61、2.73、3.93 和 1.81 个对数。本研究得出结论，靶向细菌蛋白质生物合成机制的抗生素可能导致噬菌体的裂解活性降低，从而降低其治疗潜力。因此，在将这些化合物用于联合治疗方案之前，必须对其进行仔细筛选。
