The CpxP family of bacterial chaperones: novel antibiotic targets

欧洲疾病预防中心2013年的一份报告得出的主要结论是：“尤其缺乏治疗由多重耐药(MDR)革兰氏阴性细菌引起的感染的新药物”。其中一个原因是革兰氏阴性菌(GNB)有一层外膜(OM)，使它们不能渗透，因此对许多对革兰氏阳性菌有活性的抗生素具有耐药性。沙门氏菌是一种由细菌病原体感染的全球性问题，每年约有9400万人患上胃肠炎或食物中毒。沙门氏菌感染的发病率，特别是与暴发有关的发病率，由于抗生素耐药性而加剧，这可能导致患者患上更复杂的疾病。迫切需要治疗沙门氏菌感染的新的治疗药物。一个令人兴奋的挑战是破译作为细菌耐药机制的膜不通透性的遗传、分子和生物物理基础。这可能会扩大治疗化合物的使用，将沙门氏菌目前具有抗药性的化合物包括在内。这一研究建立在我们最近的出版物基础上，这些出版物表明，CpxP伴侣蛋白家族之间存在结构和功能重叠，并且它们是沙门氏菌对抗生素耐药所必需的。我们认为，CpxP分子伴侣为沙门氏菌的治疗提供了一个潜在的新机会。

"There is a particular lack of new agents to treat infections caused by multi-drug resistant (MDR) Gram-negative bacteria" was a major conclusion from a report by the European Centre for Disease Prevention in 2013. One reason for this is Gram-negative bacteria (GNB) possess an outer membrane (OM); making them impermeable and therefore resistant to many antibiotics that are active against Gram-positives. Infection by the bacterial pathogen, Salmonella is a global issue, with approximately 94 million people contracting gastroenteritis or food poisoning each year. Morbidity of Salmonella infections, particularly associated with outbreaks, is exacerbated by antibiotic resistance, which can lead to more complicated illness in patients. Novel therapeutic agents to treat Salmonella infections are urgently required. An exciting challenge is to decipher the genetic, molecular and biophysical basis of membrane impermeability as a bacterial resistance mechanism. This could expand the use of therapeutic compounds to include those to which Salmonella are currently resistant. This studentship builds from our recent publications that demonstrated that structural and functional overlap exists between the CpxP family of chaperones, and that they are required for Salmonella resistance to antibiotics. We believe that the CpxP chaperones present a potential new opportunity to therapeutically target Salmonella.