Effect of the switch status of Helicobacter pylori Outer Inflammatory Protein A on gastric diseases

Abstract

Abstract Helicobacter pylori OipA (Outer Inflammatory Protein A) is an outer membrane protein that takes role in the adherence and colonization to the stomach. oipA gene expression is regulated by the slipped-strand mispairing mechanism through a hypermutable CT dinucleotide repeat motif in the 5΄ region. Alterations in the CT number repeats cause frame-shift mutations to result in phase variation of oipA expression. While a functional “on” status has been recognized as a risk factor for peptic ulcer diseases and gastric cancer in many studies, some controversial findings still exist. To this end, this study compiled the sequence data of oipA from 10 different studies between 2000-2019 and 50 oipA DNA sequences from our own research that examined the relationship between the phase on/off status of oipA and gastric diseases based on CT repeat number. Overall, we have reached 536 oipA DNA sequences from patients. This large collection of oipA sequences first clarified the absolute conservation of the peptide-pentamer of FWLHA for phase-on status, suggesting this pentamer as a superior marker for the determination of oipAstatus than counting the number of CT repeats. Combining the sequence and patient data, we have re-analyzed the association between the ‘‘On’’ status of oipA and gastric diseases. Our results showed a strong association between oipA‘‘On’’ status and gastric cancer supporting previous findings. We also investigated the AlphaFold2 computed structure of OipA that adopts a beta-barrel fold closely resembling to the autotransporter family of H. pylori. Altogether, this study confirms a strong association between OipA ‘‘On’’ statuses and severe gastrointestinal diseases like cancer and provides useful insights into the FWLHA pentamer as an indicator of “on” status of oipA putative autotransporter function rather than CT repeats number.