Hamway Youssef, Taxauer Karin, Moonens Kristof, Neumeyer Victoria, Fischer Wolfgang, Schmitt Verena, Singer Bernhard B, Remaut Han, Gerhard Markus, Mejías-Luque Raquel
Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, 81675 Munich, Germany.
Structural and Molecular Microbiology, VIB-VUB Center for Structural Biology, VIB, 1050 Brussels, Belgium.
Microorganisms. 2020 Mar 25;8(4):465. doi: 10.3390/microorganisms8040465.
Attachment to the host gastric mucosa is a key step in infection. Recently, a novel adhesin, HopQ, was shown to bind distinct host CEACAM proteins-an interaction that was found to be essential for the translocation of CagA, a key virulence factor of The HopQ-CEACAM1 co-crystal structure revealed a binding mode dependent on loops in HopQ that are clasped by disulfide bonds. In this study, we investigated the importance of these cysteine residues for CEACAM1 engagement by . We observed a loss of CEACAM1 binding and CagA translocation upon disruption of the disulfide bond in loop CL1 (connecting C103 to C132 in HopQ). Deletion of the Dsb-like oxidoreductase HP0231 did not affect cell surface expression of HopQ or alter the interaction of with target cells. Although HP0231 deletion was previously described to impede CagA translocation, our results indicate that this occurs through a HopQ-independent mechanism. Together, our results open up new avenues to therapeutically target the HopQ-CEACAM1 interaction and reduce the burden of pathogenic .
附着于宿主胃黏膜是感染过程中的关键步骤。最近，一种新型黏附素HopQ被证明可与不同的宿主癌胚抗原相关细胞黏附分子（CEACAM）蛋白结合，这种相互作用被发现对幽门螺杆菌关键毒力因子CagA的转位至关重要。HopQ-CEACAM1共晶体结构揭示了一种依赖于HopQ中由二硫键扣合的环的结合模式。在本研究中，我们研究了这些半胱氨酸残基对幽门螺杆菌与CEACAM1结合的重要性。我们观察到，当环CL1（在HopQ中连接C103至C132）中的二硫键被破坏时，CEACAM1结合和CagA转位丧失。缺失类Dsb氧化还原酶HP0231不影响HopQ的细胞表面表达，也不改变幽门螺杆菌与靶细胞的相互作用。尽管先前描述HP0231缺失会阻碍CagA转位，但我们的结果表明这是通过一种不依赖HopQ的机制发生的。总之，我们的结果为治疗性靶向HopQ-CEACAM1相互作用并减轻致病性幽门螺杆菌的负担开辟了新途径。
