Intestinal colonization by C.albicans and enteric bacteria

描述(申请人提供)：口咽部念珠菌病(OPC)，艾滋病患者常见的机会性感染，被认为是由白色念珠菌引起的，显然是良性地定植于患者身上。共生的白色念珠菌通常在胃肠道和女性阴道中定居，在某种程度上也会在口腔或皮肤中定居。在免疫受损的宿主中，共生定殖者经历转化为能够导致广泛疾病的侵袭性病原体。尽管共生白色念珠菌作为病原生物的来源很重要，但人们对共生定植的性质和控制它的因素知之甚少。本申请中提出的研究旨在了解白念珠菌在定植过程中的重要活动，以及白念珠菌定植对宿主生理的影响。这项拟议研究的第一个具体目标是研究白色念珠菌突变对突变株定植能力的影响。在第二个具体目标中，将检验用白色念珠菌定植会增加宿主对细菌感染的易感性的假设。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，在小鼠身上的研究表明，T细胞在限制肠道内白色念珠菌的种群数量方面发挥着重要作用。因此，很可能艾滋病患者被白念珠菌定植到很高的水平。因此，假设白色念珠菌定植引起的细菌感染的易感性增加，可能有助于艾滋病患者对腹泻疾病的易感性。当患者患上念珠菌病时，导致感染的微生物是以前在患者体内携带而不会引起疾病的微生物。尽管有许多研究考察了疾病期间发生的事件，但很少有研究专注于了解疾病发生前有机体的生长情况。这项研究项目的目的是了解生物体对寄主的定植作用，并了解定植如何影响寄主的健康，特别是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.