NovelHelicobacter pyloritherapeutic targets: the unusual suspects

Abstract

Understanding the current status of the discovery and development of anti-Helicobacter therapies requires an overview of the searches for therapeutic targets performed to date. A summary is given of the very substantial body of work conducted in the quest to find Helicobacter pylori genes that could be suitable candidates for therapeutic intervention. The products of most of these genes perform metabolic functions, and others have roles in growth, cell motility and colonization. The genes identified as potential targets have been organized into three categories according to their degree of characterization. A short description and evaluation is provided of the main candidates in each category. Investigations of potential therapeutic targets have generated a wealth of information about the physiology and genetics of H. pylori, and its interactions with the host, but have yielded little by way of new therapies.

NMR elucidation of monomer–dimer transition and conformational heterogeneity in histone‐like DNA binding protein of Helicobacter pylori

“…Hup predominantly exists as a homo‐dimer in solution and binds to genomic DNA to maintain genome integrity and regulates all DNA‐dependent cellular activities (such as replication, recombination, repair, and transcription) . However, additionally, it also plays a pivotal role in the formation of a sturdy nucleoid structure that helps protect DNA from physical damage and to some extent from denaturation under acidic gastric conditions . Overall, it provides an additional protection mechanism for H. pylori to survive and colonize persistently under harsh conditions of human stomach characterized by acidity, peristalsis, and attack by phagocytes accompanied by release of reactive oxygen species .…”

Flavodoxins as Novel Therapeutic Targets against Helicobacter pylori and Other Gastric Pathogens

“…Krebs cycle and anaerobic respiration [33,38] Glu-tRNA Gln amidotransferase, subunits A (GatA), B (GatB), and C (GatC) Protein synthesis [26,33] Coenzyme A biosynthesis [35,36] Carbon starvation protein A Starvation response, utilization of peptides, and host-pathogen interactions [37] Methylthiotransferase (MiaB) Protein synthesis [37] Ribosomal RNA small subunit methyltransferase E Protein synthesis [37] Ribosomal protein L11 methyltransferase Protein synthesis [37] Tetrapyrrole (Corrin-Porphyrin) methylase family protein Protein synthesis [37] Peptide chain release factor 1 Protein synthesis [37] Fumarate reductase (FrdA, FrdB, and FrdC) Krebs cycle and anaerobic respiration [33,38] Glu-tRNA Gln amidotransferase, subunits A (GatA), B (GatB), and C (GatC) Protein synthesis [26,33] Helicase-nuclease DNA Repair Enzymes (AddAB) DNA damage reparation [39,40] Cytochrome C-type biogenesis protein CcdA Cytochrome C synthesis [37] Cytochrome C oxidase, subunits CcoN, CcoO, CcoP and CcoQ ATP synthesis [37] Flavodoxin (Fld) Oxidative decarboxylation of pyruvate [28,[41][42][43] Table 1. Cont.…”

“…Oxidative decarboxylation of pyruvate [26,33,[44][45][46] Flavodoxin:quinone reductase (FqrB) Oxidative decarboxylation of pyruvate [33,42,46] 2-oxoglutarate:acceptor oxidoreductase, subunits A (OorA), B (OorB), C (OorC) and D (OorD) Succinyl-CoA production [26,33,45] Cell Wall Structure N-succinyl-L,L-diaminopimelic acid desuccinylase, SDAP-deacylase (DapE) Succinylase pathway (lysine biosynthesis) [17,47,48] Glutamate racemase MurI Peptidoglycan biosynthesis [49,50] cag pathogenicity island (translocation of bacterial factors (e.g., Cag A and peptidoglycan)…”

Untitled

“…Việc sử dụng các loại kháng sinh như amoxicillin, clarithromycin và metronidazole trong điều trị bệnh đường tiêu hóa bao gồm viêm loét dạ dày, u xơ và ung thư dương tính với H. pylori ngày càng gặp nhiều khó khăn do tỷ lệ kháng thuốc gia tăng nhanh chóng [2]. Nhiều nghiên cứu tập trung vào tìm kiếm các đích tác dụng phân tử mới thay thế nhằm sàng lọc các hợp chất kháng H. pylori mới tiềm năng [3,4] [3][4][5]. Nghiên cứu của Miesel và cộng sự đã chỉ ra rằng PDF đối với tế bào nhân thực chỉ có mức biểu hiện rất thấp và không đóng vai trò quan trọng [3].…”