Manna Olga Maria, Caruso Bavisotto Celeste, Gratie Melania Ionelia, Damiani Provvidenza, Tomasello Giovanni, Cappello Francesco
Pathologic Anatomy Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy.
Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Human Anatomy and Histology, University of Palermo, 90127 Palermo, Italy.
Int J Mol Sci. 2025 May 24;26(11):5065. doi: 10.3390/ijms26115065.
() is a Gram-negative bacterium that colonizes the human stomach and is associated with several gastric diseases, including gastritis, peptic ulcer disease, and gastric cancer. The bacterium's ability to thrive in the harsh gastric environment is due, to some extent, to its stress response mechanisms, with its heat shock proteins (HSPs) playing a putative, yet not fully understood, role in these adaptive processes. HSPs are a family of molecules, highly conserved throughout phylogenesis, that assist in protein folding, prevent aggregation, and ensure cellular homeostasis under stressful conditions. In , HSPs contribute to survival in the stomach's acidic environment and oxidative stress. Furthermore, they aid in the bacterium's ability to adhere to gastric epithelial cells, modulate the host immune response, and form biofilms, all contributing to chronic infection and pathogenicity. The role of microbial HSPs in antibiotic resistance has also emerged as a critical area of research, as these proteins help stabilize efflux pumps, protect essential proteins targeted by antibiotics, and promote biofilm formation, thereby reducing the efficacy of antimicrobial treatments. Among bacterial HSPs, GroEL and DnaK are probably the major proteins that control most of the 's functioning. Indeed, both proteins possess remarkable acid resistance, high substrate affinity, and dual roles in protein homeostasis and host interaction. These features make them critical for 's adaptation, persistence, and pathogenicity in the gastric niche. In addition, recent findings have also highlighted the involvement of HSPs in the crosstalk between and gastric epithelial cells mediated by the release of bacterial outer membrane vesicles and host-derived exosomes, both of these extracellular vesicles being part of the muco-microbiotic layer of the stomach and influencing cellular signalling and immune modulation. Considering their critical role in the survival and persistence of bacteria, microbial HSPs also represent potential therapeutic targets. Strategies aimed at inhibiting microbial HSP function, combined with conventional antibiotics or developing vaccines targeting microbial HSPs, could provide new avenues for the treatment of infections and combat antibiotic resistance. This review explores the multifaceted roles of microbial HSPs in the pathogenesis of , highlighting their contributions to bacterial adhesion, immune evasion, stress response, and antibiotic resistance.
（）是一种革兰氏阴性菌，定殖于人类胃部，与多种胃部疾病相关，包括胃炎、消化性溃疡病和胃癌。该细菌在恶劣胃部环境中生存的能力在一定程度上归因于其应激反应机制，其热休克蛋白（HSPs）在这些适应性过程中发挥了假定但尚未完全了解的作用。HSPs是一类在系统发育过程中高度保守的分子家族，在应激条件下协助蛋白质折叠、防止聚集并确保细胞内稳态。在（该细菌名称未给出）中，HSPs有助于在胃部酸性环境和氧化应激中存活。此外，它们有助于细菌黏附于胃上皮细胞、调节宿主免疫反应并形成生物膜，所有这些都促成慢性感染和致病性。微生物HSPs在抗生素耐药性中的作用也已成为一个关键研究领域，因为这些蛋白质有助于稳定外排泵、保护抗生素靶向的必需蛋白质并促进生物膜形成，从而降低抗菌治疗的效果。在细菌HSPs中，GroEL和DnaK可能是控制（该细菌名称未给出）大部分功能的主要蛋白质。事实上，这两种蛋白质都具有显著的耐酸性、高底物亲和力，并且在蛋白质稳态和宿主相互作用中具有双重作用。这些特性使其对于（该细菌名称未给出）在胃部生态位中的适应、持续存在和致病性至关重要。此外，最近的研究结果还强调了HSPs参与由细菌外膜囊泡和宿主来源的外泌体释放介导的（该细菌名称未给出）与胃上皮细胞之间的相互作用，这两种细胞外囊泡都是胃黏液微生物层的一部分，并影响细胞信号传导和免疫调节。鉴于它们在细菌存活和持续存在中的关键作用，微生物HSPs也代表了潜在的治疗靶点。旨在抑制微生物HSP功能的策略，与传统抗生素联合使用或开发针对微生物HSPs的疫苗，可为（该细菌名称未给出）感染的治疗和对抗抗生素耐药性提供新途径。本综述探讨了微生物HSPs在（该细菌名称未给出）发病机制中的多方面作用，强调了它们对细菌黏附、免疫逃避、应激反应和抗生素耐药性的贡献。
