Although most infected folks are asymptomatic [3], colonization of the gastric epithelial cells can cause an inflammatory response in the mucosa

Although most infected folks are asymptomatic [3], colonization of the gastric epithelial cells can cause an inflammatory response in the mucosa. is administered, humans can remain infected for life [3]. Although most infected people are asymptomatic [3], colonization of the gastric epithelial cells can cause an inflammatory response Givinostat hydrochloride in the mucosa. The initial gastritis can progress to chronic non-atrophic, active or atrophic gastritis and lead to duodenal and gastric ulcers or even to intestinal metaplasia and dysplasia, occasionally causing gastric mucosa-associated lymphoid tissue (MALT) lymphoma or gastric adenocarcinoma [3,6]. In fact, is the only bacterium classified as a Class I carcinogen by the International Agency for Research on Cancer [3,6,7] and, as shown by epidemiological studies, it seems to be the most common infectious agent related to cancers, 6.2% of all cancer cases worldwide being attributable to [6,8]. The risk of developing strain, the host traits, and the interactions between bacterium and host [9]. Besides, has been reported to be involved in extragastric pathologies such as neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, allergic, liver, and biliary diseases [10,11]. The eradication of has been recommended in order to decrease gastric mucosa inflammation and to prevent its progression to preneoplasic lesions and the development of gastric cancer and/or other extragastric diseases Givinostat hydrochloride [12,13]. Conventional treatment of infection has relied on two or three broad-spectrum antimicrobials plus a proton-pump inhibitor Givinostat hydrochloride (PPI) such as omeprazole, esomeprazole or rabeprazole. Although standard triple therapy, which is based on clarithromycin, Givinostat hydrochloride amoxicillin, or metronidazole and a PPI, has been prescribed for decades, nowadays it does not accomplish acceptable eradication rates because of resistance, especially to metronidazole and clarithromycin. In areas of high (>15%) resistance to the latter antibiotic, bismuth or non-bismuth quadruple regimens must be followed. They consist of a PPI plus three antimicrobials: metronidazole, tetracycline, and bismuth in the first therapy and metronidazole, amoxicillin, and clarithromycin in the second one [14,15]. These last regimens seem the most effective ones to overcome antibiotic resistance, the main proposed reason of treatment failure together with low patient compliance to therapy, high gastric bacterial load, cytochrome P450 polymorphism (CYP2C19), and high gastric acidity [16]. Antibiotic resistance to has been suggested to arise from point mutations, drug inactivation, the activation of drug efflux pumps, altered membrane permeability, biofilm formation or the presence of bacterial dormant forms [17]. The high genetic diversity of allows the bacterium to evade the immune response and to adapt to environment challenges such as antimicrobials [18,19]. The annual reinfection rate is up to 8.7% and depends on world region, age, education level, proportion of household members infected, and socioeconomic status of the patients [12]. While the reported prevalences of amoxicillin (0C21.4%) and tetracycline (0C32.4%) resistance are moderate, those of metronidazole (2.1C99.5%), clarithromycin (7.9C52.6%), and levofloxacin (0C55.6%) are quite high [12]. In fact, clarithromycin-resistant strains were included by the World Health Organization in the high-priority group of pathogens that urgently require novel treatments [20]. Additional therapeutic regimens have been proposed that include the use of vonoprazan, furazolidone, rifabutin, fluoroquinolones, and probiotics-containing treatments [12,13,15,21,22]. Recent works suggest that therapies against should be adapted to local antibiotic resistances, and the Maastrich V/Florence consensus report recommended, after failure Givinostat hydrochloride of second-line treatment, culture with susceptibility testing or molecular determination of genotype resistance [13,15,21,22,23]. While prophylactic or therapeutic vaccines for have been investigated, no vaccine has been developed yet, probably because of high genetic variability together with the fact that the infection downregulates the hosts immune response which highlights the importance of selecting antigens and adjuvants capable of triggering a strong host immune reaction [24,25]. Several novel therapeutic strategies for the treatment of infection have been suggested including phototherapy and the use of antimicrobial peptides, gastric mucins, polysaccharides or bioactive compounds [24]. Related to the use Rabbit Polyclonal to PLA2G4C of novel bioactive compounds, key gene products have been proposed for directed therapies [26]. One of them is flavodoxin [27,28], a small electron transfer protein involved in an essential metabolic pathway. Flavodoxin is also expressed in other gastrointestinal pathogens and also in human gut commensal bacteria. As it is essential for some commensal bacteria [29], it is important to develop flavodoxin-based therapies that are not harmful to these microorganisms in order to avoid side effects on the gastrointestinal microbiota. On the other hand, as flavodoxin is also essential for several gastrointestinal pathogens, this protein constitutes a useful target for developing specific treatments against them. In this review, we compile and discuss proteins that may act as potential targets.