Department of Biotechnology, Ghent University, Ghent, Belgium.
Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Appl Environ Microbiol. 2020 Sep 17;86(19). doi: 10.1128/AEM.01311-20.
The prevalence of extensively and pandrug-resistant strains of leaves little or no therapeutic options for treatment for this bacterial pathogen. Bacteriophages and their lysins represent attractive alternative antibacterial strategies in this regard. We used the extensively drug-resistant strain MK34 to isolate the bacteriophage PMK34 (vB_AbaP_PMK34). This phage shows fast adsorption and lacks virulence genes; nonetheless, its narrow host spectrum based on capsule recognition limits broad application. PMK34 is a member of the and has a 41.8-kb genome (50 open reading frames), encoding an endolysin (LysMK34) with potent muralytic activity (1,499.9 ± 131 U/μM), a typical mesophilic thermal stability up to 55°C, and a broad pH activity range (4 to 10). LysMK34 has an intrinsic antibacterial activity up to 4.8 and 2.4 log units for and strains, respectively, but only when a high turgor pressure is present. The addition of 0.5 mM EDTA or application of an osmotic shock after treatment can compensate for the lack of a high turgor pressure. The combination of LysMK34 and colistin results in up to 32-fold reduction of the MIC of colistin, and colistin-resistant strains are resensitized in both Mueller-Hinton broth and 50% human serum. As such, LysMK34 may be used to safeguard the applicability of colistin as a last-resort antibiotic. is one of the most challenging pathogens for which development of new and effective antimicrobials is urgently needed. Colistin is a last-resort antibiotic, and even colistin-resistant strains exist. Here, we present a lysin that sensitizes for colistin and can revert colistin resistance to colistin susceptibility. The lysin also shows a strong, turgor pressure-dependent intrinsic antibacterial activity, providing new insights in the mode of action of lysins with intrinsic activity against Gram-negative bacteria.
广泛耐药和泛耐药菌株的流行使得针对这种细菌病原体的治疗几乎没有或没有治疗选择。噬菌体及其裂解酶在这方面代表了有吸引力的替代抗菌策略。我们使用广泛耐药的 菌株 MK34 来分离噬菌体 PMK34（vB_AbaP_PMK34）。该噬菌体表现出快速吸附且缺乏毒力基因；然而，基于荚膜识别的窄宿主谱限制了其广泛应用。PMK34 是 的成员，具有 41.8-kb 基因组（50 个开放阅读框），编码一种具有强大溶壁活性的内溶素（LysMK34）（1,499.9±131 U/μM），典型的嗜温热稳定性高达 55°C，以及广泛的 pH 活性范围（4 至 10）。LysMK34 具有内在的抗菌活性，对 和 菌株分别高达 4.8 和 2.4 个对数单位，但仅在存在高膨压时才具有这种活性。添加 0.5 mM EDTA 或在处理后施加渗透压休克可以补偿缺乏高膨压的情况。LysMK34 与多粘菌素联合使用可使多粘菌素的 MIC 降低多达 32 倍，并且在 Mueller-Hinton 肉汤和 50%人血清中使多粘菌素耐药菌株重新敏感。因此，LysMK34 可用于保护多粘菌素作为最后手段抗生素的适用性。 是最具挑战性的病原体之一，迫切需要开发新的有效抗菌药物。多粘菌素是一种最后手段的抗生素，甚至存在多粘菌素耐药的 菌株。在这里，我们提出了一种溶菌酶，它使 对多粘菌素敏感，并可使多粘菌素耐药性恢复为多粘菌素敏感性。该溶菌酶还表现出强大的、依赖膨压的内在抗菌活性，为具有内在抗革兰氏阴性细菌活性的溶菌酶的作用模式提供了新的见解。
