PDF(Pubmed)
Abstract：
The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria Escherichia coli is commonly found as a commensal microbe in the human gut, some strains are dangerously pathogenic, contributing to the highest AMR-associated mortality. Strains of E. coli that can translocate from the gastrointestinal tract to distal sites, called extraintestinal E. coli (ExPEC), are particularly problematic and predominantly afflict women, the elderly, and immunocompromised populations. Despite nearly 40 years of clinical trials, there is still no vaccine against ExPEC. One reason for this is the remarkable diversity in the ExPEC pangenome across pathotypes, clades, and strains, with hundreds of genes associated with pathogenesis including toxins, adhesins, and nutrient acquisition systems. Further, ExPEC is intimately associated with human mucosal surfaces and has evolved creative strategies to avoid the immune system. This review summarizes previous and ongoing preclinical and clinical ExPEC vaccine research efforts to help identify key gaps in knowledge and remaining challenges.
摘要：
抗菌素耐药性（AMR）的出现是一个主要的全球健康危机，预计到2050年，全球每年将导致1000万人死亡。虽然革兰氏阴性菌大肠杆菌通常在人体肠道中作为共生微生物被发现，一些菌株具有危险的致病性，导致AMR相关死亡率最高。可以从胃肠道转移到远端部位的大肠杆菌菌株，称为肠外大肠杆菌（ExPEC），特别有问题，主要是折磨女性，老年人,和免疫功能低下的人群。尽管近40年的临床试验，仍然没有针对ExPEC的疫苗。其中一个原因是ExPEC全基因组在不同病理类型中的显著多样性，进化枝，和菌株，有数百个与发病机制相关的基因，包括毒素，粘附素,和营养采集系统。Further,ExPEC与人类粘膜表面密切相关，并已发展出避免免疫系统的创造性策略。这篇综述总结了以前和正在进行的临床前和临床ExPEC疫苗研究工作，以帮助确定知识和剩余挑战方面的关键差距。
