Two Remarkable Serine/leucine Polymorphisms in Helicobacter Pylori: Functional Importance for Serine Protease HtrA and Adhesin BabA

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2024 May 2

PMID 38698410

Authors

Steffen Backert

Nicole Tegtmeyer

Anselm H C Horn

Heinrich Sticht

Bodo Linz

Affiliations

Soon will be listed here.

Abstract

Single nucleotide polymorphisms (SNPs) account for significant genomic variability in microbes, including the highly diverse gastric pathogen Helicobacter pylori. However, data on the effects of specific SNPs in pathogen-host interactions are scarce. Recent functional studies unravelled how a serine/leucine polymorphism in serine protease HtrA affects the formation of proteolytically active trimers and modulates cleavage of host cell-to-cell junction proteins during infection. A similar serine/leucine mutation in the carbohydrate binding domain of the adhesin BabA controls binding of ABO blood group antigens, enabling binding of either only the short Lewis b/H antigens of blood group O or also the larger antigens of blood groups A and B. Here we summarize the functional importance of these two remarkable bacterial SNPs and their effect on the outcome of pathogen-host interactions.

References

Kennemann L, Didelot X, Aebischer T, Kuhn S, Drescher B, Droege M . Helicobacter pylori genome evolution during human infection. Proc Natl Acad Sci U S A. 2011; 108(12):5033-8. PMC: 3064335. DOI: 10.1073/pnas.1018444108. View

Moonens K, Gideonsson P, Subedi S, Bugaytsova J, Romao E, Mendez M . Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. Cell Host Microbe. 2016; 19(1):55-66. PMC: 4793151. DOI: 10.1016/j.chom.2015.12.004. View

Krebes J, Didelot X, Kennemann L, Suerbaum S . Bidirectional genomic exchange between Helicobacter pylori strains from a family in Coventry, United Kingdom. Int J Med Microbiol. 2014; 304(8):1135-46. DOI: 10.1016/j.ijmm.2014.08.007. View

Berthenet E, Yahara K, Thorell K, Pascoe B, Meric G, Mikhail J . A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk. BMC Biol. 2018; 16(1):84. PMC: 6090961. DOI: 10.1186/s12915-018-0550-3. View

Aspholm-Hurtig M, Dailide G, Lahmann M, Kalia A, Ilver D, Roche N . Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin. Science. 2004; 305(5683):519-22. DOI: 10.1126/science.1098801. View

Hatakeyama M . Impact of the Helicobacter pylori Oncoprotein CagA in Gastric Carcinogenesis. Curr Top Microbiol Immunol. 2024; 444:239-257. DOI: 10.1007/978-3-031-47331-9_9. View

Moodley Y, Linz B, Yamaoka Y, Windsor H, Breurec S, Wu J . The peopling of the Pacific from a bacterial perspective. Science. 2009; 323(5913):527-30. PMC: 2827536. DOI: 10.1126/science.1166083. View

Linz B, Sticht H, Tegtmeyer N, Backert S . Cancer-associated SNPs in bacteria: lessons from Helicobacter pylori. Trends Microbiol. 2024; 32(9):847-857. DOI: 10.1016/j.tim.2024.02.001. View

Nell S, Estibariz I, Krebes J, Bunk B, Graham D, Overmann J . Genome and Methylome Variation in Helicobacter pylori With a cag Pathogenicity Island During Early Stages of Human Infection. Gastroenterology. 2017; 154(3):612-623.e7. DOI: 10.1053/j.gastro.2017.10.014. View

10.

Tuan V, Yahara K, Dung H, Binh T, Tung P, Tri T . Genome-wide association study of gastric cancer- and duodenal ulcer-derived strains reveals discriminatory genetic variations and novel oncoprotein candidates. Microb Genom. 2021; 7(11). PMC: 8743543. DOI: 10.1099/mgen.0.000680. View

11.

Zarzecka U, Tegtmeyer N, Sticht H, Backert S . Trimer stability of Helicobacter pylori HtrA is regulated by a natural mutation in the protease domain. Med Microbiol Immunol. 2023; 212(3):241-252. PMC: 10293373. DOI: 10.1007/s00430-023-00766-9. View

12.

Moodley Y, Linz B, Bond R, Nieuwoudt M, Soodyall H, Schlebusch C . Age of the association between Helicobacter pylori and man. PLoS Pathog. 2012; 8(5):e1002693. PMC: 3349757. DOI: 10.1371/journal.ppat.1002693. View

13.

Cao P, Lee K, Blaser M, Cover T . Analysis of hopQ alleles in East Asian and Western strains of Helicobacter pylori. FEMS Microbiol Lett. 2005; 251(1):37-43. DOI: 10.1016/j.femsle.2005.07.023. View

14.

Beckett A, Loh J, Chopra A, Leary S, Lin A, McDonnell W . genetic diversification in the Mongolian gerbil model. PeerJ. 2018; 6:e4803. PMC: 5961626. DOI: 10.7717/peerj.4803. View

15.

Fischer W, Tegtmeyer N, Stingl K, Backert S . Four Chromosomal Type IV Secretion Systems in Composition, Structure and Function. Front Microbiol. 2020; 11:1592. PMC: 7366825. DOI: 10.3389/fmicb.2020.01592. View

16.

Wessler S, Posselt G . Bacterial Proteases in Helicobacter pylori Infections and Gastric Disease. Curr Top Microbiol Immunol. 2024; 444:259-277. DOI: 10.1007/978-3-031-47331-9_10. View

17.

Foegeding N, Caston R, McClain M, Ohi M, Cover T . An Overview of Helicobacter pylori VacA Toxin Biology. Toxins (Basel). 2016; 8(6). PMC: 4926140. DOI: 10.3390/toxins8060173. View

18.

Linz B, Windsor H, Gajewski J, Hake C, Drautz D, Schuster S . Helicobacter pylori genomic microevolution during naturally occurring transmission between adults. PLoS One. 2013; 8(12):e82187. PMC: 3858298. DOI: 10.1371/journal.pone.0082187. View

19.

Yamaoka Y, Saruuljavkhlan B, Alfaray R, Linz B . Pathogenomics of Helicobacter pylori. Curr Top Microbiol Immunol. 2024; 444:117-155. DOI: 10.1007/978-3-031-47331-9_5. View

20.

Zhang X, Tegtmeyer N, Traube L, Jindal S, Perez-Perez G, Sticht H . A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions. PLoS Pathog. 2015; 11(2):e1004621. PMC: 4412286. DOI: 10.1371/journal.ppat.1004621. View