H PYLORI INFECTION AND DRUG RESISTANCE IN PERU

胃病原体幽门螺杆菌（HP）感染导致胃炎 和消化性溃疡，是胃癌的危险因素，即使 大多数感染是无症状的。 我们建议：（一）卓越的 HP菌株之间的遗传多样性促成了这一系列症状， (ii)感染HP的高危人群，如秘鲁的人群， 通常携带多种菌株，以及（iii）这种共定植可能 允许水平基因转移和更快的个人特异性适应， 有助于增加毒力，并促进抗生素的传播 阻力 在FIRCA与R博士的合作中，莱昂·巴鲁阿和胃肠道 生理学工作组（GPWG）在秘鲁利马，我们将获得菌株 对母体所需的临床有用抗生素具有耐药性 政府拨款资助研究幽门螺杆菌抗药性机制及基因 实验性混合感染中HP菌株间的转移 猪仔 我们将测试和扩展上面概述的想法，以及更多 通过分析，普遍加强父母补助金中描述的研究 HP菌株活组织检查材料来自感染的秘鲁人每年访问 博士利昂·巴鲁阿的，GPWG诊所。 首先，我们将测试（a） 生活在秘鲁的人仅携带一种，而不是多种HP菌株，和（B） 居民HP人口是否倾向于改变或保持不变， 时间 这将涉及池和单个菌落的表征 HP分离株从患者，使他们经常每年访问， 在临床上，HP表征将包括表型（耐药性） 测试，和敏感和有效的任意引物PCR（RAPD）DNA 指纹分析和基于PCR的HP基因可变片段检测， 特别是与高毒力相关的那些。 第二，在合作的情况下， 定殖，我们将使用获得的表型和DNA指纹数据 为了验证HP主要在胃粘膜中生长的观点， 单细胞克隆，也许来自一个特殊的保护生态位， 少“干”细胞。 这个想法是在仔猪共感染实验中出现的 这导致了家长补助金，并得到了我们初步结果的支持， 人体活检 拟议的研究将扩大和加强家长补助金。 我们将 从我们合作者的专业知识中受益匪浅， Hp感染的流行病学和病理生理学，并从他们的特殊性 严重感染HP的患者。 作为回报，我们将提供培训 在分子遗传学上，GPWG的研究人员将提高我们的 未来几年的合作，更广泛地说，有利于秘鲁人 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.