Human Genetics Unit, Indian Statistical Institute, 203 B T Road, Kolkata 700108, India.
Biosci Rep. 2022 Mar 31;42(3). doi: 10.1042/BSR20212084.
Bacterial virulence factors are often located in their genomic islands (GIs). Helicobacter pylori, a highly diverse organism is reported to be associated with several gastrointestinal diseases like, gastritis, gastric cancer (GC), peptic ulcer, duodenal ulcer (DU) etc. A novel similarity score (Sm)-based comparative analysis with GIs of 50 H. pylori strains revealed clear idea of the various factors which promote disease progression. Two putative pathogenic GIs in some of the H. pylori strains were identified. One GI, having a putative labile enterotoxin and other dynamin-like proteins (DLPs), is predicted to increase the release of toxin by membrane vesicular formation. Another island contains a virulence-associated protein D (vapD) which is a component of a type-II toxin-antitoxin system (TAs), leads to enhance the severity of the H. pylori infection. Besides the well-known virulence factors like Cytotoxin-associated gene A (CagA) and vacA, several GIs have been identified which showed to have direct or indirect impact on H. pylori clinical outcomes. One such GI, containing lipopolysaccharide (LPS) biosynthesis genes was revealed to be directly connected with disease development by inhibiting the immune response. Another collagenase-containing GI worsens ulcers by slowing down the healing process. GI consisted of fliD operon was found to be connected to flagellar assembly and biofilm production. By residing in biofilms, bacteria can avoid antibiotic therapy, resulting in chronic infection. Along with well-studied CagA and vacuolating toxin A (vacA) virulent genes, it is equally important to study these identified virulence factors for better understanding H. pylori-induced disease prognosis.
细菌毒力因子通常位于其基因组岛(GI)中。幽门螺杆菌是一种高度多样化的生物体,据报道与多种胃肠道疾病有关,如胃炎、胃癌(GC)、消化性溃疡、十二指肠溃疡(DU)等。一项基于新型相似性评分(Sm)的 50 株幽门螺杆菌 GI 的比较分析,清晰地揭示了促进疾病进展的各种因素。在一些幽门螺杆菌菌株中鉴定出两个假定的致病 GI。一个 GI 含有一个推定的不稳定肠毒素和其他动力蛋白样蛋白(DLPs),预计通过膜泡形成增加毒素的释放。另一个岛含有一个与毒力相关的蛋白 D(vapD),它是一种 II 型毒素-抗毒素系统(TAs)的组成部分,导致幽门螺杆菌感染的严重程度增加。除了众所周知的毒力因子如细胞毒素相关基因 A(CagA)和 vacA 外,还鉴定出了几个 GI,它们显示出对幽门螺杆菌临床结果有直接或间接影响。一个含有脂多糖(LPS)生物合成基因的 GI 被揭示通过抑制免疫反应与疾病发展直接相关。另一个含有胶原酶的 GI 通过减缓愈合过程使溃疡恶化。含有 fliD 操纵子的 GI 与鞭毛组装和生物膜产生有关。通过寄居在生物膜中,细菌可以逃避抗生素治疗,导致慢性感染。除了研究得很好的 CagA 和空泡毒素 A(vacA)毒力基因外,研究这些已鉴定的毒力因子对于更好地了解幽门螺杆菌引起的疾病预后同样重要。