Abstract
Helicobacter pylori infection of the human stomach causes chronic inflammation and forms a major risk factor for the development of peptic ulcer disease and gastric cancer. Current standard eradication therapies use an acid-suppressing drug and two antibiotics, now frequently supplemented with bismuth. Declining eradication efficiencies, off-target effects of lengthy broad-spectrum antibiotic treatments and the desire of a more systematic eradication in asymptomatic H. pylori carriers to suppress gastric cancer incidence spur a search for an effective vaccine and alternative therapeutic options. Here, we review the current progress in the field, with an emphasis on narrow-spectrum or nonantibiotic therapeutics.
Highlights
Helicobacter pylori multidrug resistance is rising to the point where quadruple therapy is becoming the first-line treatment and future therapeutic efficacy is under increasing threat
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Summary
Metabolism: - shikimate pathway - succinylase pathway - coenzyme A biosynthesis - pseudaminic biosynthesis. A recent meta-analysis of randomized-controlled trials showed that preventative eradication of H. pylori can reduce the incidence of gastric cancer in healthy asymptomatic infected individuals, at least in populations with a high gastric cancer burden [25] This is likely to exacerbate the spread of drug resistance, and the health risks associated with available antibiotic treatments make large-scale deployment of H. pylori eradication programs unlikely unless novel therapeutic options or a vaccine are developed. Future H. pylori treatments: broad-spectrum antibacterial agents Most antibiotic classes in clinical use are of natural origin and have bacterio-static or -lytic properties by inhibiting household pathways such as DNA replication and protein synthesis, or by compromising membrane and cell wall integrity (Figure 1). The bacterium colonizes the gastric mucosa and inner layer of the overlying mucus, where the pH is near physiological pH 6, but can temporarily survive more acidic conditions thanks to
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