School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
Faculty of Health, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
J Bacteriol. 2024 Apr 18;206(4):e0037123. doi: 10.1128/jb.00371-23. Epub 2024 Mar 6.
is an intracellular bacterial pathogen that undergoes a biphasic developmental cycle, consisting of intracellular reticulate bodies and extracellular infectious elementary bodies. A conserved bacterial protease, HtrA, was shown previously to be essential for during the reticulate body phase, using a novel inhibitor (JO146). In this study, isolates selected for the survival of JO146 treatment were found to have polymorphisms in the acyl-acyl carrier protein synthetase gene () encodes the enzyme responsible for activating fatty acids from the host cell or synthesis to be incorporated into lipid bilayers. The isolates had distinct lipidomes with varied fatty acid compositions. A reduction in the lipid compositions that HtrA prefers to bind to was detected, yet HtrA and MOMP (a key outer membrane protein) were present at higher levels in the variants. Reduced progeny production and an earlier cellular exit were observed. Transcriptome analysis identified that multiple genes were downregulated in the variants especially stress and DNA processing factors. Here, we have shown that the fatty acid composition of chlamydial lipids, HtrA, and membrane proteins interplay and, when disrupted, impact chlamydial stress response that could trigger early cellular exit.
is an important obligate intracellular pathogen that has a unique biphasic developmental cycle. HtrA is an essential stress or virulence protease in many bacteria, with many different functions. Previously, we demonstrated that HtrA is critical for using a novel inhibitor. In the present study, we characterized genetic variants of with reduced susceptibility to the HtrA inhibitor. The variants were changed in membrane fatty acid composition, outer membrane proteins, and transcription of stress genes. Earlier and more synchronous cellular exit was observed. Combined, this links stress response to fatty acids, membrane proteins, and HtrA interplay with the outcome of disrupted timing of chlamydial cellular exit.
是一种细胞内细菌病原体，经历双相发育周期，包括细胞内网状体和细胞外感染性原体。先前已经证明，一种保守的细菌蛋白酶 HtrA 对于在网状体阶段是必不可少的，使用一种新型抑制剂（JO146）。在这项研究中，选择用于 JO146 处理存活的分离株被发现其酰基-酰基载体蛋白合成酶基因（）中有多态性，该基因编码负责激活来自宿主细胞的脂肪酸或合成物以掺入脂质双层的酶。分离株具有不同脂肪酸组成的不同脂质组。检测到 HtrA 喜欢结合的脂质组成减少，但变体中的 HtrA 和 MOMP（一种关键的外膜蛋白）水平更高。观察到后代产量减少和更早的细胞退出。转录组分析表明，变体中多个基因下调，特别是应激和 DNA 处理因子。在这里，我们已经表明，衣原体脂质、HtrA 和膜蛋白的脂肪酸组成相互作用，当受到干扰时，会影响衣原体应激反应，从而引发早期细胞退出。
是一种重要的专性细胞内病原体，具有独特的双相发育周期。HtrA 是许多细菌中一种必不可少的应激或毒力蛋白酶，具有许多不同的功能。以前，我们证明 HtrA 使用一种新型抑制剂对于是至关重要的。在本研究中，我们对具有降低对 HtrA 抑制剂敏感性的 进行了遗传变异特征分析。变体改变了膜脂肪酸组成、外膜蛋白和应激基因的转录。观察到更早和更同步的细胞退出。综合来看，这将应激反应与脂肪酸、膜蛋白和 HtrA 的相互作用与衣原体细胞退出时间中断的结果联系起来。
