假伯克霍尔德氏菌(Bpm)是一种革兰氏阴性细胞内病原体,可引起人类的类骨样病,一个被忽视的,少报,和致命的疾病,可以在超过50%的病例中达到致命的结果。它可以产生急性和慢性感染,由于细菌的细胞内生命周期及其产生“持久”休眠状态的能力,消除后者尤其具有挑战性。允许在生长表型和持久表型之间转换的分子机制尚未得到很好的理解,但据推测至少部分归因于毒素-抗毒素(TA)系统的参与。我们以前已经研究了其中一个系统(定义为HigBA)与左氧氟沙星抗生素暴露相关的特定表达模式之间的联系。通过计算机模拟方法,我们预测了另外三对编码其他推定的HigBA系统的基因的存在。因此,我们的主要目标是确定在同一家族的不同BpmTA系统中,哪些机制是保守的,哪些途径是特异性的.我们假设高患病率,有时甚至这些系统在Bpm染色体中的冗余表明它们可以相互作用,而不仅仅是单个系统,正如传统上认为的那样,,并且可能在Bpm生命周期中扮演未定义的角色。这里,我们表明,不同系统的毒素和抗毒素都有助于细菌的生存,并且同一家族的毒素在环境压力条件下可以产生累积效应。
目的:毒素-抗毒素(TA)系统在细菌的持久性中起重要作用,细菌细胞进入休眠状态或缓慢生长状态以在营养匮乏等不利条件下生存的现象,抗生素暴露,或宿主免疫反应。通过研究假伯克霍尔德菌的TA系统,我们可以深入了解这种病原体如何在宿主环境中生存和持续存在,有助于其毒力和导致类lioidosis慢性感染的能力。
Burkholderia pseudomallei (Bpm) is a Gram-negative intracellular pathogen that causes melioidosis in humans, a neglected, underreported, and lethal disease that can reach a fatal outcome in over 50% of the cases. It can produce both acute and chronic infections, the latter being particularly challenging to eliminate because of the intracellular life cycle of the bacteria and its ability to generate a \"persister\" dormant state. The molecular mechanism that allows the switch between growing and persister phenotypes is not well understood but it is hypothesized to be due at least in part to the participation of toxin-antitoxin (TA) systems. We have previously studied the link between one of those systems (defined as HigBA) with specific expression patterns associated with levofloxacin antibiotic exposure. Through in silico methods, we predicted the presence of another three pairs of genes encoding for additional putative HigBA systems. Therefore, our main goal was to establish which mechanisms are conserved as well as which pathways are specific among different Bpm TA systems from the same family. We hypothesize that the high prevalence, and sometimes even redundancy of these systems in the Bpm chromosomes indicates that they can interact with each other and not function as only individual systems, as it was traditionally thought, and might be playing an undefined role in Bpm lifecycle. Here, we show that both the toxin and the antitoxin of the different systems contribute to bacterial survival and that toxins from the same family can have a cumulative effect under environmental stressful conditions.
OBJECTIVE: Toxin-antitoxin (TA) systems play a significant role in bacterial persistence, a phenomenon where bacterial cells enter a dormant or slow-growing state to survive adverse conditions such as nutrient deprivation, antibiotic exposure, or host immune responses. By studying TA systems in Burkholderia pseudomallei, we can gain insights into how this pathogen survives and persists in the host environment, contributing to its virulence and ability to cause melioidosis chronic infections.