Oktem-Okullu Sinem, Karaman Tayyip, Akcelik-Deveci Sümeyye, Timucin Emel, Sezerman Osman Ugur, Mansur-Ozen Nesteren, Buyukcolak Yaren, Tiftikci Arzu
Department of Medical Microbiology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey.
Department of Medical Biotechnology, Institute of Health and Science, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey.
AMB Express. 2023 Oct 10;13(1):109. doi: 10.1186/s13568-023-01621-z.
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 oipA status 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.
幽门螺杆菌OipA(外炎症蛋白A)是一种外膜蛋白,在胃的黏附和定植过程中发挥作用。oipA基因表达通过5΄区域中一个高度可变的CT二核苷酸重复基序,由滑链错配机制调控。CT重复数目的改变会导致移码突变,从而引起oipA表达的相位变异。虽然在许多研究中,功能性“开启”状态已被认为是消化性溃疡疾病和胃癌的一个危险因素,但仍存在一些有争议的发现。为此,本研究汇总了2000年至2019年间10项不同研究中的oipA序列数据,以及我们自己研究中的50条oipA DNA序列,这些研究基于CT重复数研究了oipA的相位“开启/关闭”状态与胃部疾病之间的关系。总体而言,我们从患者中获得了536条oipA DNA序列。这一大量的oipA序列首次阐明了“开启”状态下FWLHA肽五聚体的绝对保守性,表明该五聚体作为确定oipA状态的标记物比计算CT重复数更具优势。结合序列和患者数据,我们重新分析了oipA的“开启”状态与胃部疾病之间的关联。我们的结果显示oipA“开启”状态与胃癌之间存在强关联,支持了先前的发现。我们还研究了AlphaFold2计算的OipA结构,其采用了一种与幽门螺杆菌自转运蛋白家族非常相似的β桶折叠结构。总之,本研究证实了oipA“开启”状态与癌症等严重胃肠道疾病之间存在强关联,并为FWLHA五聚体作为oipA推定自转运蛋白功能“开启”状态的指标而非CT重复数提供了有用的见解。