Questions about the behaviour of bacterial pathogens in vivo
Questions about the behaviour of bacterial pathogens in vivo
复制标题
DOI：
10.1098/rstb.2000.0597
复制
发表时间：
2000-05-29
影响因子：
6.3
通讯作者：
Smith, H
中科院分区：
文献类型：
--
作者：
Smith, H
细菌性病原体在人和动物中引起疾病。它们具有独特的生物学特性，使它们能够在黏液表面定植，穿透黏液表面，在宿主环境中生长，抑制或避开宿主防御，破坏宿主胸围。负责这五种生物需求的细菌产物是致病性的决定因素（毒力决定因素）。目前的知识来自体外研究，但现在对细菌如何在感染宿主内表现和产生毒力决定因素的兴趣正在增加。有三个方面需要阐明：细菌的活动，影响它们的宿主因素和两者之间的代谢相互作用。第一个相对容易实现，最近已经设计了新的方法来实现这一点。第二种方法并不容易，因为体内环境的复杂性及其不断变化的面貌。然而，可以从文献和新的方法中获得一些信息。第三个方面很难有效地研究，除非体内的一些事件可以在体外模拟。讨论会议的目的是描述这些新方法，并展示它们和传统研究如何揭示细菌病原体在体内的活动。本文提出了一些问题，并举例说明了如何回答这些问题。细菌在体内生长是致病性的首要条件。如果没有生长，其他四个要求的决定因素就不适合医学。新方法的结果强调了这一点。重要的问题如下。感染的发展模式是什么？细菌在不同阶段的生长速度和数量？什么营养物质在9中存在，它们如何随着感染的进展而变化，并与生长速度和人口规模有关？这些营养物质是如何代谢的，通过什么细菌机制？哪些细菌过程处理可能出现的营养缺乏和拮抗条件？传统方法和新方法可以回答第一个问题和第二个问题的一部分；举例说明。讨论了试图回答后两个问题的困难。至于在体内产生粘膜定植、渗透、干扰宿主防御和损害宿主的决定因素，这里有一些关键问题。已被体外研究确认的推定决定因素是否在体内产生？它们是否与毒力有关？迄今为止未知的毒力决定因素可以通过检查体内生长的细菌来识别吗？毒力决定因子的补体是否随着感染的进行而改变？体外识别的调节过程，如ToxR/ToxS、PhoP/PhoQ、群体感应和III型分泌，在体内是否有效？什么环境因素影响体内毒力决定因素的产生，通过什么代谢过程？例子表明，在大多数情况下，前四个问题的答案是肯定的，但不是全部。试图回答最后一个，也是最难的问题，也描述了。最后，本文描述了宿主来源的胞苷5′-单磷酸- n -乙酰神经氨酸对淋球菌体内脂多糖的唾液化作用，以及大多数乳酸的作用。这项研究揭示了一种新的细菌致病性的重要组成部分，宿主因子负责其生产和代谢参与。
Bacterial pathogens cause disease in man and animals. They have unique biological properties, which enable them to colonize mucous surfaces, penetrate them, grow in the environment of the host, inhibit or avoid host defences and damage the bust. The bacterial products responsible for these five biological requirements are the determinants of pathogenicity (virulence determinants). Current knowledge comes from studies in vitro, but now interest is increasing in how bacteria behave and produce virulence determinants within the infected host. There are three aspects to elucidate: bacterial activities, the host factors that affect them and the metabolic interactions between the two. The first is relatively easy to accomplish and, recently new methods for doing this have been devised. The second is not easy because of the complexity of the environment in vivo and its ever-changing face. Nevertheless, some information can be gained from the literature and by new methodology. The third aspect is very difficult to study effectively unless some events in vivo can be simulated in vitro.The objectives of the Discussion Meeting were to describe the new methods and to show how they, and conventional studies, are revealing the activities of bacterial pathogens in vivo. This paper sets the scene by raising some questions and suggesting, with examples, how they might be answered.Bacterial growth in vivo is the primary requirement for pathogenicity. Without growth, determinants of the other four requirements are not for med. Results from the new methods are underlining this point. The important questions are as follows. What is the pattern of a developing infection and the growth rates and population sizes of the bacteria at different stages? What nutrients are present in nine and how do they change as infection progresses and relate to growth rates and population sizes? How are these nutrients metabolized and by what bacterial mechanisms? Which bacterial processes handle nutrient deficiencies and antagonistic conditions that may arise? Conventional and new methods can answer the first question and part of the second; examples are described. The difficulties of trying to answer the last two are discussed.Turning to production in vivo of determinants of mucosal colonization, penetration, interference with host defence and damage to the host, here are the crucial questions. Are putative determinants, which have been recognized by studies in vitro, produced in vivo and are they relevant to virulence? Can hitherto unknown virulence determinants be recognized by examining bacteria grown in vivo? Does the complement of virulence determinants change as infection proceeds? Are regulatory processes recognized in vitro, such as ToxR/ToxS, PhoP/PhoQ, quorum sensing and type III secretion, operative in vivo? What environmental factors affect virulence determinant production in vivo and by what metabolic processes? Examples indicate that the answers to the first four questions are 'yes' in most but not all cases. Attempts to answer the last, and most difficult, question are also described.Finally, sialylation of the lipopolysaccharide of gonococci in vivo by host-derived cytidine 5'-monophospho-N-acetyl neuraminic acid, and the effect of most lactate are described. This investigation revealed a new bacterial component important in pathogenicity the host factors responsible for its production and the metabolism involved.