Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, S-223 62, Sweden.
Department of Urology, South-Pest Hospital, Budapest 1204, Hungary.
Microbiol Spectr. 2016 Jun;4(3). doi: 10.1128/microbiolspec.UTI-0019-2014.
A paradigm shift is needed to improve and personalize the diagnosis of infectious disease and to select appropriate therapies. For many years, only the most severe and complicated bacterial infections received more detailed diagnostic and therapeutic attention as the efficiency of antibiotic therapy has guaranteed efficient treatment of patients suffering from the most common infections. Indeed, treatability almost became a rationale not to analyze bacterial and host parameters in these larger patient groups. Due to the rapid spread of antibiotic resistance, common infections like respiratory tract- or urinary-tract infections (UTIs) now pose new and significant therapeutic challenges. It is fortunate and timely that infectious disease research can offer such a wealth of new molecular information that is ready to use for the identification of susceptible patients and design of new suitable therapies. Paradoxically, the threat of antibiotic resistance may become a window of opportunity, by encouraging the implementation of new diagnostic and therapeutic approaches. The frequency of antibiotic resistance is rising rapidly in uropathogenic organisms and the molecular and genetic understanding of UTI susceptibility is quite advanced. More bold translation of the new molecular diagnostic and therapeutic tools would not just be possible but of great potential benefit in this patient group. This chapter reviews the molecular basis for susceptibility to UTI, including recent advances in genetics, and discusses the consequences for diagnosis and therapy. By dissecting the increasingly well-defined molecular interactions between bacteria and host and the molecular features of excessive bacterial virulence or host-response malfunction, it is becoming possible to isolate the defensive from the damaging aspects of the host response. Distinguishing "good" from "bad" inflammation has been a long-term quest of biomedical science and in UTI, patients need the "good" aspects of the inflammatory response to resist infection while avoiding the "bad" aspects, causing chronicity and tissue damage.
需要进行范式转变，以改善和个性化传染病的诊断，并选择适当的治疗方法。多年来，只有最严重和复杂的细菌感染得到了更详细的诊断和治疗关注，因为抗生素治疗的效率保证了患有最常见感染的患者的有效治疗。事实上，可治疗性几乎成为了不在这些更大的患者群体中分析细菌和宿主参数的理由。由于抗生素耐药性的迅速传播，像呼吸道或尿路感染（UTI）这样的常见感染现在带来了新的和重大的治疗挑战。幸运的是，传染病研究能够提供如此丰富的新分子信息，这些信息已经准备好用于识别易感患者和设计新的合适治疗方法。具有讽刺意味的是，抗生素耐药性的威胁可能成为一个机会之窗，通过鼓励实施新的诊断和治疗方法。在尿路病原体中，抗生素耐药性的频率迅速上升，对 UTI 易感性的分子和遗传理解已经相当先进。在这个患者群体中，更大胆地转化新的分子诊断和治疗工具不仅是可能的，而且具有很大的潜在益处。本章回顾了 UTI 易感性的分子基础，包括遗传学的最新进展，并讨论了对诊断和治疗的影响。通过剖析细菌和宿主之间日益明确的分子相互作用以及细菌过度毒力或宿主反应功能障碍的分子特征，有可能将宿主反应的防御和破坏方面分开。区分“好”和“坏”炎症一直是生物医学科学的长期追求，在 UTI 中，患者需要炎症反应的“好”方面来抵抗感染，同时避免“坏”方面导致慢性和组织损伤。
