Doctoral Dissertation Research: Antimicrobial resistance as a form of anthropogenic disturbance to primate gut microbiomes

抗菌素耐药性现在被认为是一个紧迫的公共卫生问题，已蔓延到世界各地城市和自然环境的微生物群落中。直到最近，抗菌素耐药性才被确定为环境污染物和生态问题；它对野生动物及其环境的影响仍然相对未知。这个博士论文项目将在不同的环境条件下描述和量化灵长类物种及其栖息地的抗菌素耐药性。除了研究濒危物种和脆弱环境的抗菌素耐药性外，这项研究还将强调耐药细菌在宿主（包括人类）及其环境之间传播的可能性。这项研究的结果将与科学界（通过合作、演讲、参加国内和国际会议和出版物）和公众（通过科学教育和外展）分享，对非人灵长类动物的保护和饲养具有深远的价值。尽管抗生素的普遍使用对现代社会具有革命性意义，但它已导致抗生素耐药基因的快速发展，这些基因持续存在于细菌基因组中，可以转移到其他微生物中，并可能使环境中的耐药库增殖。动物可通过直接接触抗生素（例如通过兽医护理）或接触被抗生素或耐药细菌污染的环境而获得耐药细菌。一旦被纳入宿主相关的微生物群落，耐药细菌就会破坏共生微生物的共生作用，并削弱宿主的免疫功能。目前对耐药性传播和影响的了解主要来自对人类和临床突出的动物模型（即实验室啮齿动物）的研究。为了更好地理解和更全面地应对无处不在的“耐药性危机”，一个更广泛的生态框架是必要的。Co-PI的论文研究重点是评估抗菌素耐药性作为人为干扰的一个新方面，它对沿干扰梯度（即从最小到极大干扰的自然栖息地和圈养环境）生活的狐猴产生不同的影响。利用新一代测序技术，该项目有三个具体目标：确定(1)狐猴肠道微生物组的抗生素耐药性丰度，(2)狐猴栖息地具有代表性的环境微生物组（来自土壤和水），以及(3)直接经历急性和累积抗生素暴露的狐猴肠道微生物组。通过研究狐猴及其环境中的各种干扰，我们将确定抗微生物药物耐药性的具体来源，并强调耐药性危机是一个生态和保护问题，可能影响全世界的野生动物。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Antimicrobial resistance, now considered a pressing public health concern, has propagated into the microbial communities of urban and natural environments around the world. Only recently has antimicrobial resistance been identified as an environmental contaminant and ecological concern; its impacts on wildlife and their environments remain relatively unknown. This doctoral dissertation project will characterize and quantify antimicrobial resistance in a primate species and its habitats, across different environmental conditions. Beyond contextualizing antimicrobial resistance in an endangered species and vulnerable landscape, this research will highlight the potential for transmission of resistant bacteria between hosts, including humans, and their environments. With far-reaching value for nonhuman primate conservation and husbandry, the results of this study will be shared with the scientific community (via collaborations, presentations, attendance of domestic and international conferences, and publications) and with the public (via science education and outreach).Although revolutionary for modern society, the ubiquitous use of antibiotics has resulted in the rapid development of antimicrobial resistance genes that persist in bacterial genomes, can be transferred to other microbes, and may be proliferating environmental reservoirs of resistance. Animals can acquire resistant bacteria either through exposure to direct antibiotic administration (e.g., through veterinary care) or to environments contaminated with antibiotics or resistance bacteria. Once incorporated into host-associated communities, known as microbiomes, resistant bacteria disrupt the symbiotic roles of commensal microbes and diminish the host’s immune function. Current understanding about the transmission and impacts of resistance derives primarily from studies of humans and clinically prominent animal models (i.e., laboratory rodents). To better understand and combat the ubiquitous ‘resistance crisis’ on a more comprehensive scale, a broader, ecological framework is necessary. The Co-PI’s dissertation research is focused on assessing antimicrobial resistance as a novel facet of anthropogenic disturbance that differentially impacts lemurs living along a gradient of disturbance (i.e., ranging from minimally to greatly disturbed natural habitats and captive settings). Using next-generation sequencing techniques, this project has three specific aims: to determine the abundance of antimicrobial resistance in (1) the gut microbiome of lemurs, (2) representative environmental microbiomes (from soil and water) across the lemurs’ habitats, and (3) the gut microbiome of lemurs directly experiencing acute and cumulative antibiotic exposure. By studying varying disturbances in lemurs and their environments, we will determine specific sources of antimicrobial resistance and highlight the resistance crisis as an ecological and conservation concern with the potential to impact wildlife worldwide.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.