Mycolyltransferase is important for biofilm formation and pathogenesis of <i>Tsukamurella</i> keratitis

<i>Tsukamurella</i>, a group of multi-drug resistant, Gram-positive, aerobic, and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the pathogenesis of <i>Tsukamurella</i> keratitis is largely unknown. To address this, we used New Zealand White rabbits to develop the first eye infection model and conducted <i>in vitro</i> tests to study the pathogenesis mechanisms of <i>Tsukamurella</i>. There is increasing evidence that biofilms play a significant role in ocular infections, leading us to hypothesize that biofilm formation is crucial for effective <i>Tsukamurella</i> infection. In order to look for potential candidate genes which are important in biofilm formation and <i>Tsukamurella</i> keratitis. We performed genome sequencing of two ocular isolates, <i>T. pulmonis</i>-PW1004 and <i>T. tyrosinosolvens</i>-PW899, to identify potential virulence factors. Through <i>in vitro</i> and <i>in vivo</i> studies, we characterized their biological roles in mediating <i>Tsukamurella</i> keratitis. Our findings confirmed that <i>Tsukamurella</i> is an ocular pathogen by fulfilling Koch's postulates, and using genome sequence data, we identified <i>tmytC,</i> encoding a mycolyltransferase, as a crucial gene in biofilm formation and causing <i>Tsukamurella</i> keratitis in the rabbit model. This is the first report demonstrating the novel role of mycolyltransferase in causing ocular infections. Overall, our findings contribute to a better understanding of <i>Tsukamurella</i> pathogenesis and provide a potential target for treatment. Specific inhibitors targeting TmytC could serve as an effective treatment option for <i>Tsukamurella</i> infections.

冢村菌属（Tsukamurella）是一类多药耐药、革兰氏阳性、需氧且部分抗酸的细菌，现已成为细菌性结膜炎与角膜炎的新兴致病菌。然而，冢村菌属角膜炎的发病机制目前尚未完全阐明。为填补这一研究空白，本研究以新西兰白兔构建了首个眼部感染模型，并开展体外（in vitro）实验以探究冢村菌属的致病机制。越来越多的研究证据表明，生物膜在眼部感染中发挥关键作用，据此我们提出假说：生物膜形成对于冢村菌属的有效感染至关重要。为筛选在生物膜形成及冢村菌属角膜炎中发挥关键作用的潜在候选基因，我们对两株眼部分离株——肺炎冢村菌（T. pulmonis）-PW1004与溶酪素冢村菌（T. tyrosinosolvens）-PW899进行了全基因组测序，以鉴定潜在毒力因子。通过体外（in vitro）与体内（in vivo）实验，我们表征了这些毒力因子在介导冢村菌属角膜炎过程中的生物学功能。本研究通过科赫法则（Koch's postulates）验证了冢村菌属为眼部致病菌，并结合基因组测序数据，鉴定出编码分枝菌酸转移酶的tmytC基因是家兔模型中生物膜形成与冢村菌属角膜炎致病的关键基因。本研究为首项证实分枝菌酸转移酶在眼部感染中具有全新致病作用的报道。综上，本研究成果加深了人们对冢村菌属致病机制的理解，并为其治疗提供了潜在靶点：针对TmytC的特异性抑制剂有望成为治疗冢村菌属感染的有效手段。

搜集汇总

背景与挑战

背景概述

该数据集聚焦于Tsukamurella角膜炎的发病机制研究，通过基因组测序和实验验证，首次揭示mycolyltransferase基因（tmytC）在生物膜形成和感染过程中的关键作用。研究确认了Tsukamurella作为眼部病原体，并提出了针对TmytC的抑制剂作为潜在治疗靶点，为理解这种多重耐药细菌的感染机制提供了新见解。