Influence of oipA Phase Variation on Virulence Phenotypes Related to Type IV Secretion System in Helicobacter pylori

• Published in: Helicobacter (Cambridge, Mass.) Vol. 29; no. 5; pp. e13140 - n/a
• Main Authors: Lai, Jing, Angulmaduwa, Sacheera, Kim, Myeong‐A, Kim, Aeryun, Tissera, Kavinda, Cho, Yong‐Joon, Cha, Jeong‐Heon
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2024
• Subjects: Antigens, Bacterial - genetics; Antigens, Bacterial - metabolism; Bacteria; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cell morphology; Complementation; Elongation; Gastric cancer; Gene sequencing; Genetic diversity; H. pylori; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - genetics; Helicobacter pylori - pathogenicity; Helicobacter pylori - physiology; Humans; In vitro methods and tests; Interleukin-8 - genetics; Interleukin-8 - metabolism; Molecular modelling; oipA; OipA gene; Outer membrane proteins; Pathogenicity; Pathogens; phase variation; Phase variations; Phenotype; Phenotypes; Phenotypic variations; Phosphorylation; T4SS; Type IV Secretion Systems - genetics; Type IV Secretion Systems - metabolism; Virulence; Virulence - genetics; Virulence Factors - genetics; Virulence Factors - metabolism; Whole genome sequencing; H. pylori; T4SS; oipA; phase variation
• ISSN: 1083-4389; 1523-5378; 1523-5378
• DOI: 10.1111/hel.13140

ABSTRACT Background oipA, an outer membrane protein of Helicobacter pylori, is linked to IL‐8 induction and gastric inflammation, but its role is debated due to inconsistent findings. This study aims to explore the role of oipA phase variation in modulating the virulence traits of H. pylori, a bacterium strongly associated with the development of gastric cancer. Material and Methods American clinical isolate AH868 strain for naturally occurring phase variations of the oipA gene, and G27 strain for in vitro–induced phase variations were used to elucidate oipA's impact on key virulence phenotypes, including cell elongation, CagA phosphorylation, and IL‐8 induction. Results Using AH868 strain, natural oipA phase variation does not affect cell elongation and IL‐8 induction. Interestingly, however, in vitro–induced oipA phase variations in G27 strain uncovered that 9.4% of oipA “Off” transformants exhibit reduced cell elongation while all maintaining consistent IL‐8 induction levels. Additionally, complementation of oipA “Off to On” status restores the cell elongation phenotype in 12.5% of transformants, highlighting the importance of oipA in maintaining normal cell morphology. Crucially, these variations in cell elongation are not linked to changes in bacterial adherence capabilities. Furthermore, the study shows a correlation among oipA phase variation, cell elongation, and CagA phosphorylation, suggesting that oipA influences the functionality of the Type IV secretion system. Whole‐genome sequencing of selected transformants reveals genetic variations in bab paralogue, cagY gene, and other genomic regions, underscoring the complex genetic interactions that shape H. pylori's virulence. Conclusions Our research provides new insights into the subtle yet significant role of oipA phase variation in H. pylori pathogenicity, emphasizing the need for further studies to explore the intricate molecular mechanisms involved. This understanding could pave the way for targeted therapeutic strategies to mitigate the impact of H. pylori on human health.