Novel small molecules affecting cell membrane as potential therapeutics for avian pathogenic Escherichia coli.,Scientific Reports

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Novel small molecules affecting cell membrane as potential therapeutics for avian pathogenic Escherichia coli.
Scientific Reports ( IF 3.8 ) Pub Date : 2018-Oct-17 , DOI: 10.1038/s41598-018-33587-5
Dipak Kathayat ₁ , Yosra A Helmy ₁ , Loic Deblais ₁ , Gireesh Rajashekara ₁

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Avian pathogenic Escherichia coli (APEC), a most common bacterial pathogen of poultry, causes multiple extra-intestinal diseases in poultry which results in significant economic losses to the poultry industry worldwide. In addition, APEC are a subgroup of extra-intestinal pathogenic E. coli (ExPEC), and APEC contaminated poultry products are a potential source of foodborne ExPEC infections to humans and transfer of antimicrobial resistant genes. The emergence of multi-drug resistant APEC strains and the limited efficacy of vaccines necessitate novel APEC control approaches. Here, we screened a small molecule (SM) library and identified 11 SMs bactericidal to APEC. The identified SMs were effective against multiple APEC serotypes, biofilm embedded APEC, antimicrobials resistant APECs, and other pathogenic E. coli strains. Microscopy revealed that these SMs affect the APEC cell membrane. Exposure of SMs to APEC revealed no resistance. Most SMs showed low toxicity towards chicken and human cells and reduced the intracellular APEC load. Treatment with most SMs extended the wax moth larval survival and reduced the intra-larval APEC load. Our studies could facilitate the development of antimicrobial therapeutics for the effective management of APEC infections in poultry as well as other E. coli related foodborne zoonosis, including APEC related ExPEC infections in humans.

中文翻译：

影响细胞膜的新型小分子作为禽致病性大肠杆菌的潜在疗法。

禽致病性大肠杆菌（APEC）是家禽最常见的细菌性病原体，可引起家禽多种肠外疾病，给全球家禽业造成重大经济损失。此外，APEC 是肠外致病性大肠杆菌 (ExPEC) 的一个亚群，APEC 污染的家禽产品是人类食源性 ExPEC 感染和抗菌素耐药基因转移的潜在来源。多重耐药 APEC 菌株的出现和疫苗功效有限，需要新的 APEC 控制方法。在这里，我们筛选了一个小分子（SM）库，并鉴定了 11 个对 APEC 具有杀菌作用的 SM。已鉴定的 SM 可有效对抗多种 APEC 血清型、生物膜嵌入的 APEC、抗菌药物耐药性 APEC 和其他致病性大肠杆菌菌株。显微镜检查显示这些 SM 影响 APEC 细胞膜。SMs 暴露于 APEC 后未发现抵抗力。大多数 SM 对鸡和人类细胞表现出低毒性，并减少细胞内 APEC 负荷。大多数 SM 的处理延长了蜡蛾幼虫的存活率并减少了幼虫内的 APEC 负荷。我们的研究可以促进抗菌疗法的开发，以有效管理家禽中的 APEC 感染以及其他大肠杆菌相关的食源性人畜共患病，包括人类中与 APEC 相关的 ExPEC 感染。

更新日期：2018-10-17

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