Intestinal colonization by C.albicans and enteric bacteria

描述（由申请人提供）：口咽念珠菌病（OPC）是艾滋病患者中一种常见的机会性感染，据信是由白色念珠菌引起的，这些念珠菌显然是良性的定菌。共栖白色念珠菌通常寄生于胃肠道和女性阴道，在某种程度上也寄生于口腔或皮肤。在免疫功能低下的宿主中，共生的定植体经历转化为能够引起广泛疾病的侵入性病原体。尽管共生白色念珠菌是致病生物的重要来源，但人们对共生定植的性质和控制它的因素知之甚少。本研究旨在了解白色念珠菌定殖过程中重要的活动，以及白色念珠菌定殖对宿主生理的影响。提出的研究的第一个具体目的是研究白色念珠菌突变对突变体定植能力的影响。在第二个特定目标中，将测试白色念珠菌定殖导致宿主对细菌感染易感性增加的假设。由于OPC在艾滋病患者中的高发病率，很可能艾滋病患者经常被白色念珠菌定植。此外，对小鼠的研究表明，T细胞在限制肠道白色念珠菌种群规模方面很重要。因此，白色念珠菌很可能是艾滋病患者的高水平定植。白色念珠菌定殖引起的对细菌感染易感性增加的假设可能因此导致艾滋病患者对腹泻病的易感性。当患者患念珠菌病时，导致感染的微生物是以前在患者体内携带而不引起疾病的生物体。尽管有许多研究调查了疾病期间发生的事件，但很少有研究关注疾病发生前生物体的生长情况。本研究项目的目标是了解微生物如何在宿主体内定植，并了解定植如何影响宿主的健康，特别强调它对肠道病原体感染过程的影响。

DESCRIPTION (provided by applicant): Oropharyngeal candidiasis (OPC), a common opportunistic infection in AIDS patients, is believed to arise from Candida albicans organisms that were apparently benignly colonizing the patient. Commensal C. albicans organisms typically colonize the GI tract and female vagina, and to some extent the oral cavity or the skin. In an immunocompromised host, commensal colonizers undergo a conversion to invasive pathogens that are capable of causing a wide spectrum of diseases. Although commensal C. albicans is thus important as the source of pathogenic organisms, little is known about the nature of commensal colonization and the factors that control it. The research proposed in this application seeks to understand C. albicans activities that are important during colonization and the effect of C. albicans colonization on host physiology. The first specific aim of the proposed research is to study the effects of C. albicans mutations on the ability of mutants to colonize. In the second specific aim, the hypothesis that colonization with C. albicans results in increased host susceptibility to bacterial infection will be tested. Because of the high incidence of OPC in AIDS patients, it is likely that AIDS patients are frequently colonized by C. albicans. In addition, studies in mice indicate the T cells are important in limiting the population size of C. albicans in the intestinal tract. Therefore, it is likely that AIDS patients are colonized to high level by C. albicans. The hypothesized increase in susceptibility to bacterial infection caused by C. albicans colonization may thus contribute to the susceptibility of AIDS patients to diarrheal disease. When a patient develops candidiasis, the organisms responsible for the infection are organisms that were previously carried in the patient's body without causing disease. Although there are many studies that have examined the events that occur during disease, few studies have focused on learning about the growth of the organism before disease arises. The goal of this research project is to understand what the organism does to colonize the host and to understand how colonization affects the health of the host with particular emphasis on its influence on the course of infection by enteric pathogens.