The Forgotten Virulence Factor: The ‘non-conventional’ Hemolysin TlyA And Its Role in Helicobacter pylori Infection

Abstract

Helicobacter pylori is a human-specific Gram-negative pathogenic bacterium which colonizes the gastric mucosal layer in the stomach causing diseases such as peptic ulcer, adenocarcinoma, and gastric lymphoma. It is estimated that approximately half of the world's population is infected with H. pylori making it the most intensively characterized microbial pathogen up to now. Hemolysis has been suggested to significantly contribute to colonization of the stomach and disease progression by H. pylori. In a number of earlier studies, TlyA was characterized as a putative pore-forming cytolysin. Although a few observations in the literature suggest a role for TlyA as significant virulence factor of H. pylori, the molecular and structural characterization of this protein is much curtailed at present. Given the intensive characterization of numerous H. pylori virulence factors over the past decade, surprisingly little information exists for the TlyA toxin and its significance for pathogenesis. This review provides a brief overview on microbial hemolysis and its role for pathogenesis and discusses recent research efforts aimed at an improved understanding of the role of the 'non-conventional' hemolysin and its associated RNA methyltransferase TlyA from H. pylori.

Characterization of <b><i>Helicobacter pylori tlyA</i></b> and Its Association with Bacterial Density

“…Its molecular and structural characterization is much finite at present. There is presently no study examining on tlyA at the population level, and previous studies have only reported that certain H. pylori strains possess this gene [30]. Our study also showed that tlyA was present in all of the H. pylori isolates obtained from Indonesia.…”

“…It is therefore likely that TlyA plays an important role in the pathogenesis of H. pylori , although the hemolysis observed with human erythrocytes appeared to be weak when compared to the erythrocytes of different animals [13]. Previous studies have reported on how the hemolytic activity is extremely crucial in survivability of several bacteria, such as Listeriolysin O, a hemolysin produced by Listeria monocytogenes that promotes the release of bacteria from phagosomes to the cytosol and HlyA, a hemolysin generated by E. coli that has been reported to induce predominant pro-inflammatory cytokines in the colonization and infection process, such as IL-6 and IL-8 [30]. Regrettably, the mechanism of hemolysis caused by H. pylori and the role of the components involved in it only been characterized to a limited extend.…”

“…However, it is likely related to the change in the multimeric structure of TlyA caused by different types of amino acids at the position 138 (threonine in TlyA1 and lysine in TlyA2). This change might be associated with more virulent TlyA1 variants in colonizing the gastric mucosa [30]. In addition to being a determinant of the virulence levels, variations of this amino acid sequence may become the marker to distinguish TlyA1 from TlyA2.…”

“…Successful colonization of H. pylori was noted, as assessed from the bacterial density in the gastric mucosa. A study conducted in the UK detected that H. pylori strain with mutation in the tlyA resulted in a decreased ability to attach with the AGS cells and that it was unable to colonize the stomach of the experimental animals [15, 30]. Interestingly, the correlation between tlyA and H. pylori density was not noted in the corpus.…”

Genomic Characterization of Arcobacter butzleri Isolated From Shellfish: Novel Insight Into Antibiotic Resistance and Virulence Determinants

“…One of the few differences between these strains is the presence in Ab 6V of the hemolysin tyl C gene which codes for a protein with a conserved protein/cyclin M (CNNM) transmembrane domain, while, in Ab 55, we found only a precursor of hemolysin C. In both genomes, we identified the RNA methyltransferase hemolysin A ( tyl A), which encodes for a 16S/23S rRNA (cytidine-2′- O )-methyltransferase that is considered a virulence factor in H. pylori infection and probably acts as a pore-forming toxin (Javadi and Katzenmeier, 2016).…”