Does stripping the cell wall promote survival of Burkholderia in an infected host?

假马利氏伯克氏菌是类鼻疽病的病原体，这种疾病主要与东南亚和北澳大利亚有关。目前尚无针对类鼻疽病的既定治疗方法或疫苗。在极端的环境条件下存活并引起可能重新激活的潜伏感染，使得这种病原体很难根除，导致复发感染率很高。由于这些特点，假芽孢杆菌对人体健康和生物防御具有重要意义。了解伯克氏菌在体内的生存机制将有可能深入了解为什么伯克氏菌对治疗如此耐药。已发表的研究表明，在4C的饥饿条件下，产生的假芽孢杆菌细胞不能在标准培养基中生长，并表现出从棒状到圆形球形形态的转变。这也可以在其他细菌中看到，如枯草芽孢杆菌，并假设是所谓的l型的形成。这些细胞壁缺陷形式避免了一系列针对细胞壁相关分子的抗生素的杀菌活性。越来越多的证据表明，l型病毒在人体中产生，可能是治疗失败和反复感染的原因。最近的一篇论文表明，大肠杆菌l型是导致反复尿路感染的原因。该项目旨在制定一种体外形成伯克霍尔德菌的方案，并在感染的巨噬细胞中检测l型。我们还将探讨驱动l型和主动生长态之间转换的分子机制。该项目的结果将更好地了解这种特殊的细菌形式，它有可能是许多其他治疗失败的原因。

Burkholderia pseudomallei is the causative agent of Melioidosis, a disease predominantly linked to South East Asia and Northern Australia. Currently there are no established treatments or vaccines for Melioidosis. Surviving extreme environmental conditions and causing latent infections which can become reactivated make this pathogen very hard to eradicate, leading to high rates of recurrent infection. B. pseudomallei is of importance for both human health and biodefense due to these features. Understanding the survival mechanisms in vivo will potentially give insights into why Burkholderia are so resistant to treatments. Published research indicates that starvation conditions at 4C leads to the generation of B. pseudomallei cells which cannot grow in standard media and show a conversion from rods to a rounded coccoid morphology. This can also be seen in other bacteria such as Bacillus subtilis and hypothesized to be the formation of so-called L-forms. These cell wall deficient forms avoid the bactericidal activity from an array of antibiotics which target cell wall related molecules. Increasing evidence suggests L-forms are generated in humans and could be reason for failed treatment and recurrent infections. A recent paper shows Eschericia coli L-forms were responsible for recurrent urinary tract infections. This project will be aimed to produce a protocol for in vitro L-form formation of Burkholderia species and the detection of L-forms in infected macrophages. The molecular mechanisms which are employed to drive the switching between L-form and actively growing states will also be explored. The results of this project will give a better insight into this special bacterial form which has potential to be the cause of many other treatment failures.