Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California, USA.
Infect Immun. 2012 Oct;80(10):3713-20. doi: 10.1128/IAI.00407-12. Epub 2012 Jul 16.
Different disease outcomes of Helicobacter pylori infection correlate with distinct inflammation patterns. These different inflammatory distributions may be initiated by differences in bacterial localization. One H. pylori property known to affect murine stomach localization is chemotaxis, the ability to move in response to chemical cues. In this report, we used nonchemotactic mutants (Che(-)) to analyze whether chemotaxis is required for initial colonization of particular stomach regions or for subsequent growth therein. We found that H. pylori behaves differently in the corpus, antrum, and corpus-antrum transition zone subregions of the stomach. This outcome suggests that these regions contain unique chemotactic signals. In the corpus, H. pylori utilizes chemotaxis for initial localization but not for subsequent growth. In contrast, in the antrum and the corpus-antrum transition zone, chemotaxis does not help initial colonization but does promote subsequent proliferation. To determine which chemoreceptor is responsible for the corpus-antrum phenotypes, we infected mice with strains lacking each chemoreceptor. Strains lacking TlpA, TlpB, or TlpC displayed only modest deviations from the wild-type phenotype, while strains lacking TlpD resembled the Che(-) mutant in their antral colonization defect and fared even worse than the Che(-) mutant in the corpus. Additional analysis showed that inflammation is worse in the antrum than in the corpus in both wild-type and Che(-) mutant infections. These results suggest that chemotaxis, specifically, that controlled by TlpD, is necessary for H. pylori to survive or grow in the environment of increased inflammation in the antrum.
幽门螺杆菌感染的不同疾病结果与不同的炎症模式相关。这些不同的炎症分布可能是由细菌定位的差异引起的。已知幽门螺杆菌的一个特性会影响其在鼠胃中的定位,这一特性就是趋化性,即对化学信号做出反应的运动能力。在本报告中,我们使用非趋化性突变体(Che(-))来分析趋化性是否是幽门螺杆菌初始定植特定胃区或随后在其中生长所必需的。我们发现,幽门螺杆菌在胃的体部、胃窦部和体窦交界区这三个区域的行为不同。这一结果表明这些区域含有独特的趋化信号。在体部,幽门螺杆菌利用趋化性进行初始定位,但不需要后续生长。相比之下,在胃窦部和体窦交界区,趋化性无助于初始定植,但能促进后续增殖。为了确定哪个趋化受体负责体窦表型,我们用缺失每个趋化受体的菌株感染小鼠。缺失 TlpA、TlpB 或 TlpC 的菌株仅表现出与野生型表型的轻微偏离,而缺失 TlpD 的菌株在其胃窦定植缺陷方面类似于 Che(-)突变体,并且在体部的表现甚至比 Che(-)突变体更差。进一步的分析表明,在野生型和 Che(-)突变体感染中,炎症在胃窦部比在体部更严重。这些结果表明,趋化性,特别是由 TlpD 控制的趋化性,是幽门螺杆菌在胃窦部炎症环境中生存或生长所必需的。