Molecular Mechanisms of Antibiotic Resistance and Novel Treatment Strategies for Helicobacter pylori Infections

Abstract

Helicobacter pylori infects approximately 50% of the world’s population and is considered the major etiological agent of severe gastric diseases, such as peptic ulcers and gastric carcinoma. Increasing resistance to standard antibiotics has now led to an ever-decreasing efficacy of eradication therapies and the development of novel and improved regimens for treatment is urgently required. Substantial progress has been made over the past few years in the identification of molecular mechanisms which are conducive to resistant phenotypes as well as for efficient strategies to counteract strain resistance and to avoid the use of ineffective antibiotics. These involve molecular testing methods, improved salvage therapies, and the discovery of novel and potent antimicrobial compounds. High rates of prevalence and gastric cancer are currently observed in Asian countries, including Japan, China, Korea, and Taiwan, where concomitantly intensive research efforts were initiated to explore advanced eradication regimens aimed at reducing the risk of gastric cancer. In this review, we present an overview of the known molecular mechanisms of antibiotic resistance and discuss recent intervention strategies for H. pylori diseases, with a view of the research progress in Asian countries.

The Silent Threat: Antimicrobial-Resistant Pathogens in Food-Producing Animals and Their Impact on Public Health

“…The primary antibiotics used in H. pylori treatment are clarithromycin, amoxicillin, and metronidazole. Clarithromycin resistance has become increasingly common and has been associated with treatment failure rates of up to 40% [ 43 ]. In addition, resistance to other antibiotics, such as tetracycline and levofloxacin, has also been reported [ 42 ].…”

“…Salmonella is a Gram-negative bacterium that can cause salmonellosis, a common foodborne illness that causes gastroenteritis (including diarrhea, fever, and abdominal cramps), typhoid fever, and bacteremia. These bacteria can invade the intestinal wall and enter the bloodstream, where they can cause sepsis and other serious complications [ 43 ]. It can also lead to reduced growth and productivity in farming operations [ 52 ].…”

Antiurease Activity of Antibiotics: In Vitro, In Silico, Structure Activity Relationship, and MD Simulations of Cephalosporins and Fluoroquinolones

“…Helicobacter pylori (HP) infection is prevalent in about 1/2 of the world’s population and is an etiological agent linked with peptic ulcer, gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. 1 HP is a microaerophilic Gram-negative bacteria associated with nongastric diseases, including iron-deficiency anemia and idiopathic thrombocytopenic purpura. 2 Various treatment regimens include triple therapy, quadruple therapy, sequential therapy, and levofloxacin-based triple therapy that should eradicate HP up to 90% ( Table 1 ).…”

Antimicrobial combinations against Helicobacter pylori including benzoxadiazol-based flavodoxin inhibitors: in vitro characterization

“…These alternatives should result in higher eradication rates, provide good patient compliance, and prevent the increase in Hp antimicrobial resistance. Among the different strategies available, the development of drugs with specific targets for Hp seems promising, and key Hp gene products have been proposed for directed therapies ( 13 – 15 ). One of them is flavodoxin ( Hp -fld), a small electron transfer protein involved in an essential Hp metabolic pathway that is absent in vertebrates ( 16 , 17 ).…”