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抗噬菌体链霉菌和其泰乐菌素生物活性代谢产物可作为抗生素的替代品。

Phage-resistant Streptomyces abietis and its telomycin bioactive metabolite as a possible alternative to antibiotics.

机构信息

Department of Microbiology, Ain Shams University, Faculty of Science, 11566, Egypt.

Department of Microbiology, Faculty of Veterinary Medicine, Zagazig University, 44511, Egypt.

出版信息

Microb Pathog. 2024 Sep;194:106822. doi: 10.1016/j.micpath.2024.106822. Epub 2024 Jul 22.

DOI:10.1016/j.micpath.2024.106822
PMID:39047802
Abstract

Multidrug-resistant pathogens are now thought to be the primary global causes of disease and death. Therefore, it is imperative to develop new effective bioactive compounds from microbial sources, such as Streptomyces species. Nevertheless, the pharmaceutical industry suffered financial losses and low-quality end products as a result of Streptomyces bacteriophage contamination. To reduce the likelihood of phage-induced issues in the medical industry, it is crucial to develop a method for finding phage-resistant strains. Hence, we aimed to isolate and characterize Streptomyces spp. and Streptomyces phages from various rhizospheric soil samples in Egypt and to investigate their antibacterial activities. Moreover, we targeted development of a Streptomyces phage-resistant strain to extract its active metabolites and further testing its antibacterial activity. Herein, the antibacterial activities of the isolated 58 Streptomyces isolates showed that 10 (17.2 %) Streptomyces isolates had antibacterial activities against the tested bacteria including Listeria monocytogenes, E. coli O157, Acinetobacter baumannii, methicillin resistant-vancomycin-intermediate Staphylococcus aureus (MRSA-VISA) and Micrococcus luteus. Three lytic bacteriophages (ϕPRSC1, ϕPRSC2, and ϕPRSC4) belonging to the families Siphoviridae and Podoviridae were obtained from the rhizospheric soil samples using the most potent S. abietis isolate as the host strain. The three isolated Streptomyces phages were thermostable, ultraviolet stable, infectious, and had a wide range of hosts against the 10 tested Streptomyces isolates with antibacterial activities. The DNA of the ϕPRSC1 and ϕPRSC4 phages were resistant to digestion by EcoRI and HindIII, but the DNA of ϕPRSC2 was resistant to digestion by EcoRI and sensitive to digestion by HindIII. Of note, we developed a S. abietis strain resistant to the three isolated phages and its antibacterial activities were twice that of the wild strain. Finally, telomycin was recognized as an antibacterial metabolite extracted from phage-resistant S. abietis strain, which was potent against the tested Gram-positive bacteria including L. monocytogenes, MRSA-VISA, and M. luteus. Thus, our findings open new horizons for researching substitute antimicrobial medications for both existing and reemerging illnesses.

摘要

多药耐药病原体现在被认为是疾病和死亡的主要全球原因。因此,从微生物来源(如链霉菌属)开发新的有效生物活性化合物是当务之急。然而,由于链霉菌噬菌体的污染,制药行业遭受了财务损失和低质量的终端产品。为了减少噬菌体在医药行业引发问题的可能性,开发一种寻找抗噬菌体菌株的方法至关重要。因此,我们旨在从埃及不同根际土壤样本中分离和鉴定链霉菌属和链霉菌噬菌体,并研究它们的抗菌活性。此外,我们旨在开发一种抗链霉菌噬菌体的菌株来提取其活性代谢物,并进一步测试其抗菌活性。在这里,分离的 58 株链霉菌的抗菌活性表明,10(17.2%)株链霉菌对测试细菌具有抗菌活性,包括单核细胞增生李斯特菌、大肠杆菌 O157、鲍曼不动杆菌、耐甲氧西林-万古霉素中间金黄色葡萄球菌(MRSA-VISA)和微球菌。使用最有效的 S. abietis 分离株作为宿主菌株,从根际土壤样本中获得了属于 Siphoviridae 和 Podoviridae 家族的三种裂解噬菌体(ϕPRSC1、ϕPRSC2 和 ϕPRSC4)。三种分离的链霉菌噬菌体具有热稳定性、耐紫外线性、传染性和广泛的宿主范围,可对抗具有抗菌活性的 10 株测试链霉菌分离株。ϕPRSC1 和 ϕPRSC4 噬菌体的 DNA 对 EcoRI 和 HindIII 的消化具有抗性,但 ϕPRSC2 的 DNA 对 EcoRI 的消化具有抗性,而对 HindIII 的消化敏感。值得注意的是,我们开发了一种抗三种分离噬菌体的 S. abietis 菌株,其抗菌活性是野生菌株的两倍。最后,telomycin 被鉴定为从抗噬菌体 S. abietis 菌株中提取的一种抗菌代谢物,对测试的革兰氏阳性菌包括单核细胞增生李斯特菌、MRSA-VISA 和微球菌均有效。因此,我们的研究结果为研究替代现有和新出现疾病的抗菌药物开辟了新的前景。

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