Evaluating the Contribution of the Predicted Toxin-Antitoxin System HigBA to Persistence, Biofilm Formation, and Virulence in Burkholderia pseudomallei.
Evaluating the Contribution of the Predicted Toxin-Antitoxin System HigBA to Persistence, Biofilm Formation, and Virulence in Burkholderia pseudomallei.
复制标题
评估预测的毒素-抗毒素系统 HigBA 对类鼻疽伯克霍尔德杆菌的持久性、生物膜形成和毒力的贡献。
DOI：
10.1128/iai.00035-22
复制
发表时间：
2022
影响因子：
3.1
通讯作者：
Torres,AlfredoG
中科院分区：
文献类型：
--
作者：
Chapartegui-González,Itziar;Khakhum,Nittaya;Stockton,JacobL;Torres,AlfredoG
类meliosis是一种未被报道的人类疾病，由革兰氏阴性细胞内病原体假麦氏伯克氏菌（Bpm）引起。治疗和清除病原体都具有挑战性，复发率高导致潜伏感染。这与细菌持久性现象有关，这是一种生长抑制策略，允许细菌在压力条件下存活，例如在抗生素治疗的情况下，在易感克隆群体中。在分子水平上，这种现象与毒素-抗毒素（TA）系统的存在有关。我们对bpmk96243基因组进行了注释，并选择了11对编码这些TA系统的基因，并在不同条件下（超致死抗生素条件下；细胞内存活细菌）评估了它们的表达。通过构建突变体进一步研究高b毒素（BPSL3343）及其抗毒素HigA （BPS_RS18025）。与野生型（WT）菌株相比，在不同条件下评估了两个突变体（ΔhigBand ΔhigBΔhigA）的表型。ΔhigBtoxin突变体在巨噬细胞上表现出细胞内存活缺陷，这种表型在左氧氟沙星治疗后被消除。我们发现，在左氧氟沙星诱导的持续条件下，毒素的缺失提供了优于WT菌株的优势。抗毒素的缺乏也导致了对评估条件的不同反应，在某些条件下，它恢复了WT表型，总体上表明毒素和抗毒素成分在持续诱导的bpm表型中都起作用。
Melioidosis is an underreported human disease caused by the Gram-negative intracellular pathogen Burkholderia pseudomallei (Bpm). Both the treatment and the clearance of the pathogen are challenging, with high relapse rates leading to latent infections. This has been linked to the bacterial persistence phenomenon, a growth arrest strategy that allows bacteria to survive under stressful conditions, as in the case of antibiotic treatment, within a susceptible clonal population. At a molecular level, this phenomenon has been associated with the presence of toxin–antitoxin (TA) systems. We annotated theBpmK96243 genome and selected 11 pairs of genes encoding for these TA systems, and their expression was evaluated under different conditions (supralethal antibiotic conditions; intracellular survival bacteria). The predicted HigB toxin (BPSL3343) and its predicted antitoxin HigA (BPS_RS18025) were further studied using mutant construction. The phenotypes of two mutants (ΔhigBand ΔhigBΔhigA) were evaluated under different conditions compared to the wild-type (WT) strain. The ΔhigBtoxin mutant showed a defect in intracellular survival on macrophages, a phenotype that was eliminated after levofloxacin treatment. We found that the absence of the toxin provides an advantage over the WT strain, in bothin vitroandin vivomodels, during persister conditions induced by levofloxacin. The lack of the antitoxin also resulted in differential responses to the conditions evaluated, and under some conditions, it restored the WT phenotype, overall suggesting that both toxin and antitoxin components play a role in the persister-induced phenotype inBpm.