The Human Milk Glycome as a Defense Against Infectious Diseases: Rationale, Challenges, and Opportunities.
The Human Milk Glycome as a Defense Against Infectious Diseases: Rationale, Challenges, and Opportunities.
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DOI：
10.1021/acsinfecdis.7b00209
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发表时间：
2018-02-09
影响因子：
5.3
通讯作者：
Townsend SD
中科院分区：
文献类型：
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作者：
Craft KM;Townsend SD
每年有超过 300 万人死于传染病，其中大多数是生活在低收入和中等收入国家的穷人和幼儿。传染病的出现有多种原因。在社会方面，原因包括公共卫生标准、国际旅行和移民（出于金融、公民和社会原因）的崩溃。在分子水平上，现代传染病的兴起与耐药病原体的并存和新抗菌药物的缺乏有关。其结果是，人类有可能回到抗生素出现之前的时代，数百万人将死于本来应该是微不足道的疾病。考虑到其中的利害关系，化学界必须在为临床开发提供新的抗生素先导化合物方面发挥领导作用。我们相信这可以通过两个领域的创新来实现。首先是开发新型化学支架来治疗由多重耐药病原体引起的感染。第二个领域并不局限于第一个领域，是产生不会对宿主或宿主微生物组造成附带损害的抗生素。两者都可以通过化学合成的进步来实现。正是考虑到这一基本原理，我们假设母乳寡糖 (HMO) 可以作为抗菌开发的新型化学支架。我们在此提供我们实验室在使用 HMO 防御传染病这一目标方面取得的进展的个人叙述。
Each year over 3 million people die from infectious diseases with most of these deaths being poor and young children who live in low- and middle-income countries. Infectious diseases emerge for a multitude of reasons. On the social front, reasons include a breakdown of public health standards, international travel, and immigration (for financial, civil, and social reasons). At the molecular level, the modern rise of infectious diseases is tied to the juxtaposition of drug-resistant pathogens and a lack of new antimicrobials. The consequence is the possibility that humankind will return to the preantibiotic era wherein millions of people will perish from what should be trivial illnesses. Given the stakes, it is imperative that the chemistry community take leadership in delivering new antibiotic leads for clinical development. We believe this can happen through innovation in two areas. First is the development of novel chemical scaffolds to treat infections caused by multidrug-resistant pathogens. The second area, which is not exclusive to the first, is the generation of antibiotics that do not cause collateral damage to the host or the host’s microbiome. Both can be enabled through advances in chemical synthesis. It is with this general philosophy in mind that we hypothesized human milk oligosaccharides (HMOs) could serve as novel chemical scaffolds for antibacterial development. We provide herein a personal account of our laboratory’s progress toward the goal of using HMOs as a defense against infectious diseases.