H PYLORI INFECTION AND DRUG RESISTANCE IN PERU

幽门螺杆菌(Hp)感染引起胃炎 和消化性溃疡，是胃癌的危险因素，尽管 大多数感染都是无症状的。我们提出：(I)非凡的 幽门螺杆菌菌株之间的遗传多样性导致了这一系列症状， (Ii)感染幽门螺杆菌的高危人群，如秘鲁境内的人群， 通常携带多个菌株，以及(Iii)这种共生可能 允许水平基因转移和更快的针对个人的适应， 有助于提高毒力，并促进抗生素的传播 抵抗。 在FIRCA与R.Leon Barua博士和胃肠道的合作中 在秘鲁利马的生理工作组(GPWG)，我们将获得菌株 对父母所需的临床有用的抗生素产生抗药性 幽门螺杆菌耐药机制及基因研究资助 幽门螺杆菌实验性合并感染过程中菌株间的转移 小猪。我们将测试和扩展上面概述的想法，以及更多 通过分析分析，全面加强家长拨款中描述的研究 幽门螺杆菌从每年访问受感染的秘鲁人那里分离出活检材料 莱昂·巴鲁亚医生，GPWG诊所。首先，我们将测试(A)多久一次 居住在秘鲁的人只携带一种Hp菌株，而不是多种Hp菌株，以及(B) 惠普常住人口是倾向于变化还是保持不变 时间到了。这将涉及池塘和单个菌落的特征 每年反复就诊的患者的幽门螺杆菌分离株 临床、幽门螺杆菌的特征将包括表型(耐药性) 检测和敏感高效的随机引物聚合酶链式反应(随机扩增)DNA 对HP基因的可变片段进行指纹分析和基于PCR的检测， 尤其是那些与高毒力相关的病毒。第二，在共同-- 定植，我们将使用获得的表型和DNA指纹数据 以验证幽门螺杆菌主要生长在胃粘膜中的观点 单细胞克隆，可能来自一个特殊的保护利基，由非常 很少的干细胞。这个想法是在仔猪联合感染实验中产生的 这导致了父母的资助，并得到了我们的初步结果的支持 人类的活组织检查。 拟议的研究将扩大和加强家长助学金。我们会 从我们的合作者的专业知识中获益良多 幽门螺杆菌感染的流行病学和病理生理学及其特殊性 一组重度Hp感染的患者。作为回报，我们将提供培训 在分子遗传学方面向GPWG研究人员致敬，这将增强我们的 未来几年的合作，更广泛地说，使秘鲁人受益 科学界。

Infection by the gastric pathogen Helicobacter pylori (HP) causes gastritis and peptic ulcers, and is a risk factor for gastric cancer, even though most infections are asymptomatic. We propose that (i) the remarkable genetic diversity among HP strains contributes to this range of symptoms, (ii) that persons at high risk of HP infection, such as those in Peru, often carry multiple strains, and (iii) that such co-colonization might allow horizontal gene transfer and faster person-specific adaptation, contribute to increased virulence, and facilitate the spread of antibiotic resistance. In this FIRCA collaboration with Dr. R. Leon Barua and the Gastrointestinal Physiology Working Group (GPWG) in lima, peru, we will obtain strains resistant to clinically useful antibiotics that are needed in the parent grant for studies of HP antibiotic resistance mechanisms and on gene transfer between HP strains during experimental coinfection of gnotobiotic piglets. We will test and extend the ideas sketched above, and more generally enhance the research described in the parent grant by analyzing HP strains biopsy material from infected Peruvians making annual visits to Dr. Leon Barua's, GPWG clinic. First, we will test (a) how frequently persons living in Peru carry just one, vs. multiple HP strains, and (b) whether resident HP populations tend to change or remain constant over time. This will involve characterization of pools and of single colony isolates of HP from patients that making their recurrent annual visits to the clinic, HP characterizations will include phenotypic (drug resistance) tests, and sensitive and efficient arbitrarily primed PCR (RAPD) DNA fingerprinting, and PCR-based tests for variable segments of HP genes, especially those associated with high virulence. Second, in cases of co- colonization, we will use the phenotypic and DNA fingerprint data obtained above to test an idea that HP grows in the gastric mucosal primarily a single cell clones, perhaps from a special protected niche occupied by very few 'stem" cells. This idea emerged during piglet coinfection experiments that led to the parent grant, and is supported by our preliminary results with human biopsies. The proposed research will extend and enhance the parent grant. We will benefit immensely from the expertise of our collaborators in the epidemiology and pathophysiology of Hp infection, and from their special set of heavily HP-infected patients. In return, we will provide training in molecular genetics to GPWG researchers that will enhance our collaboration for years to come, and more generally, benefit the Peruvian scientific community.