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

Re-sensitising XDR biofilms using a combination of bacteriophage cocktails and colistin: a natural approach
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DOI:
10.1101/2022.02.04.479063
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发表时间:
2022-02
期刊:
bioRxiv
影响因子:
--
通讯作者:
N. D. Devanga Ragupathi;D. M. Muthuirulandi Sethuvel;M. Gopikrishnan;D. Murugan;R. Juliet;M. Majhi;Malathi Murugesan;G. C;Leshan Wannigama;P. Monk;E. Karunakaran;B. Veeraraghavan
N. D. Devanga Ragupathi;D. M. Muthuirulandi Sethuvel;M. Gopikrishnan;D. Murugan;R. Juliet;M. Majhi;Malathi Murugesan;G. C;Leshan Wannigama;P. Monk;E. Karunakaran;B. Veeraraghavan
中科院分区:
其他
文献类型:
--
作者:
N. D. Devanga Ragupathi;D. M. Muthuirulandi Sethuvel;M. Gopikrishnan;D. Murugan;R. Juliet;M. Majhi;Malathi Murugesan;G. C;Leshan Wannigama;P. Monk;E. Karunakaran;B. Veeraraghavan

文献摘要

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持续使用抗生素导致抗菌素耐药性的上升,对多药耐药(MDR)和广泛耐药(XDR)细菌的选择有限或没有选择。这需要替代疗法来有效地对抗对最后手段抗生素具有抗性的临床病原体。该研究调查了医院污水作为噬菌体的潜在来源来控制MDR/XDR细菌病原体。对81份样本进行了针对选定临床病原体的细菌学筛查。分离到10株抗A. baumannii,对K. pneumoniae和16个针对铜绿假单胞菌获得的抗体。观察到新的芽孢杆菌是菌株特异性的,具有长达6小时的完全生长抑制。噬菌体加粘菌素组合进一步降低粘菌素的MBEC高达16倍。值得注意的是,在0.5-1 μg/ml黏菌素浓度下,混合物表现出最高的功效,完全杀灭。因此,对临床菌株具有特异性的抗生素在治疗医院病原体方面具有更高的优势,其具有经证实的抗生物膜功效。此外,噬菌体基因组的分析显示,密切的系统发育关系,从欧洲,中国和其他邻国的报道。这项研究可作为参考,并可扩展到其他抗生素和噬菌体类型,以评估最佳协同组合,以对抗正在进行的AMR危机中的各种耐药病原体。
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 µg/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.