Waldman Abraham J, Balskus Emily P
Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
ACS Infect Dis. 2018 Jan 12;4(1):14-26. doi: 10.1021/acsinfecdis.7b00232. Epub 2017 Dec 13.
Despite significant advances in treating infectious diseases worldwide, morbidity and mortality associated with pathogen infection remains extraordinarily high and represents a critical scientific and global health challenge. Current strategies to combat these infectious agents include a combination of vaccines, small molecule drugs, increased hygiene standards, and disease-specific interventions. While these approaches have helped to drastically reduce the incidence and number of deaths associated with infection, continued investment in current strategies and the development of novel therapeutic approaches will be required to address these global health threats. Recently, human- and vector-associated microbiotas, the assemblages of microorganisms living on and within their hosts, have emerged as a potentially important factor mediating both infection risk and disease progression. These complex microbial communities are involved in intricate and dynamic interactions with both pathogens as well as the innate and adaptive immune systems of their hosts. Here, we discuss recent findings that have illuminated the importance of resident microbiotas in infectious disease, emphasizing opportunities for novel therapeutic intervention and future challenges for the field. Our discussion will focus on four major global health threats: tuberculosis, malaria, HIV, and enteric/diarrheal diseases. We hope this Perspective will highlight the many opportunities for chemists and chemical biologists in this field as well as inspire efforts to elucidate the mechanisms underlying established disease correlations, identify novel microbiota-based risk factors, and develop new therapeutic interventions.
尽管全球在治疗传染病方面取得了重大进展，但与病原体感染相关的发病率和死亡率仍然极高，这是一项严峻的科学和全球健康挑战。当前对抗这些感染因子的策略包括疫苗、小分子药物、提高卫生标准以及针对特定疾病的干预措施。虽然这些方法有助于大幅降低与感染相关的发病率和死亡人数，但仍需要持续投入当前策略并开发新的治疗方法来应对这些全球健康威胁。最近，与人类和媒介相关的微生物群，即生活在宿主及其体内的微生物群落，已成为介导感染风险和疾病进展的一个潜在重要因素。这些复杂的微生物群落与病原体以及宿主的固有免疫和适应性免疫系统都参与了复杂而动态的相互作用。在此，我们讨论了最近的研究发现，这些发现揭示了常驻微生物群在传染病中的重要性，强调了新型治疗干预的机会以及该领域未来面临的挑战。我们的讨论将聚焦于四大全球健康威胁：结核病、疟疾、艾滋病病毒和肠道/腹泻疾病。我们希望这篇观点文章能突出该领域化学家和化学生物学家面临的众多机会，并激发人们努力阐明既定疾病关联背后的机制，识别基于微生物群的新风险因素，以及开发新的治疗干预措施。
