Helicobacter pylori – 2010

Abstract

Helicobacter pylori, discovered 27 years ago, has remained the most prevalent infectious agent in the world. In the author's hypothesis, the increase of peptic ulcer prevalence in the 19-20th century could be attributable to the extended worldwide use of gastric tubes for secretory testing which led to the iatrogenic transmission of pathogenic strains. Helicobacter pylori outer membrane proteins (OMP), and duodenal ulcer promoting (dupA) proteins were identified as novel virulence factors, leading to the production of pro-inflammatory cytokines, which could be future targets of therapy. There is no ideal first-line eradication of the infection and according to expert's opinion, the efficiency of these regimens has fallen gradually in recent years to unacceptably low levels; however, in the author's opinion this is a multifactorial phenomenon which can not be generalized. As alternative drugs, the efficiency of levofloxacin, furazolidone and rifabutin has been proven by meta-analyses. Sequential and bismuth-free quadruple therapies, although highly efficient, are not yet used on a large scale. The recurrence of the infection is 2.27%/year in developed and of 13.0%/year in developing countries. Spontaneous eradication occurred in 8-20% of the children and 5-11% of adults. The prevalence of clarithromycin resistance is increasing worldwide. In Hungary, it has reached 10.9% in county cities, according to a national survey. In a district of Budapest called Ferencváros, the prevalence between 2005 and 2009 was 16-22%, with no increasing trend. The development of enzymatic inhibitors (urease, carbonic anhydrase and gamma-glutamyl transpeptidase), modified antibiotics and efflux pump inhibitors seem promising ways because these compounds do not lead to resistance; however, none have yet been used in humans.

Bacterial ι-carbonic anhydrase: a new active class of carbonic anhydrase identified in the genome of the Gram-negative bacterium Burkholderia territorii

“…It has been demonstrated in vivo that the bacterial growth at ambient CO 2 concentration is dependent on CA activity for several species, such as in the organisms discussed below 11,12 . Thus, CAs encoded in the genome of Helicobacter pylori, are essential for the acid acclimatisation of the pathogen within the stomach [13][14][15] ; Vibrio cholerae uses CAs as a system to colonise the host since CAs are involved in the production of sodium bicarbonate, which induces cholera toxin expression 16 ; Brucella suis needed functional CAs for growing [17][18][19][20] ; b-CA from Salmonella enterica is highly expressed during the bacterial infection 21 . Finally, the deletion of the gene encoding for the b-CA in Pseudomonas aeruginosa (psCA1) impaired virulence of the pathogen by reducing calcium salt depositions 22 .…”

The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for Escherichia coli Life Cycle

“…Many CA inhibitors (CAIs) exist and efficiently inhibit, in vitro, the activity of the CAs encoded by the genome of several pathogens [13,[16][17][18]. It has been demonstrated that CAIs are also effective in vivo, impairing the growth and virulence of several pathogens responsible of human diseases, such as Helicobacter pylori [19][20][21], Vibrio cholerae [22], Brucella suis [23][24][25][26], Salmonella enterica [27], and Pseudomonas aeruginosa [28]. Considering the three major criteria typifying the drug-target approach, it is evident that CAs meet the criteria (b) and (c) entirely.…”

Carbonic Anhydrases: New Perspectives on Protein Functional Role and Inhibition in Helicobacter pylori

“…In P. aeruginosa (psCA1), a Gram-negative bacterium commonly found in the environment, the β-CA gene's deletion provoked a reduction of calcium salt depositions, impairing the microbe virulence (Lotlikar et al, 2019). Finally, it was demonstrated that various CAs encoded by the H. pylori genome are essential for the acid tolerance/adaptation of the microbe in the stomach, a harsh environment with pH values as low as 1-2 (Buzas, 2010;Modak et al, 2019).…”