This photo shoes bacterial colonies in a culture in the laboratory. Credit: João Gama & Francisco Dionísio, IGC & Univ. Lisbon
为什么结核分枝杆菌仅仅有为数不多的细菌便可以引起肺结核，为什么霍乱弧菌必须在宿主内注入数以百万计的菌体才能够引起霍乱呢？近日，来自法国和葡萄牙的两个研究小组共同在近日的一篇研究报告中回答了此问题，研究人员表示，可以侵入或者破坏人体免疫系统细胞的细菌具有很高的感染性，因为这些细菌可以自由移动、复制速度很快，而且细菌之间可以进行有效交流，这样就可以将很多细菌组织起来引起严重的感染，研究者的研究对于理解细菌感染的类别有着重要的作用，而且可以精确的预测，来预测这些细菌的进化机制以及给公众的健康提供合理的建议，相关研究成果已于近日刊登在了国际杂志PloS Pathogen上。
尽管病原菌可以利用多种途径、机制来感染人体的细胞，但是两个小组的研究者发现了细菌感染机制共同的方式，研究者们查阅了48种病原菌的相关感染机制，以及他们的运动性、生长比率、和免疫细胞之间的作用方式等等，最终研究者们得出了一个值ID50，即在50%感染的细胞中能够引起感染的最小的细菌细胞的数量。
研究小组发现，细菌细胞的ID需要达到250左右才能完全的摧毁吞噬细胞，尽管细菌的ID50达到3000万的时候，引发传染的概率也微乎其微，细菌在机体内的感染需要不断生长增殖，通过细菌独有的群体感应系统来进行交流。
文章的第一作者Joao Gama表示，在机体免疫系统和促使疾病的细菌之间，有些细菌通过正面来攻击免疫细胞，而有些细菌则秘密地搞地下活动，来袭击宿主的免疫系统，很多时候，细菌都是一会正面攻击，一会秘密攻击宿主细胞的，我们的研究发现，低的ID50表明细菌是秘密攻击免疫细胞的，而高的ID50则表明细菌是通过正面来对细胞进行攻击的。（生物谷：T.Shen编译）
doi:10.1371/journal.ppat.1002503
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Immune Subversion and Quorum-Sensing Shape the Variation in Infectious Dose among Bacterial Pathogens
João Alves Gama1,2, Sophie S. Abby3,4, Sara Vieira-Silva3,4, Francisco Dionisio1,2, Eduardo P. C. Rocha3,4*
Many studies have been devoted to understand the mechanisms used by pathogenic bacteria to exploit human hosts. These mechanisms are very diverse in the detail, but share commonalities whose quantification should enlighten the evolution of virulence from both a molecular and an ecological perspective. We mined the literature for experimental data on infectious dose of bacterial pathogens in humans (ID50) and also for traits with which ID50 might be associated. These compilations were checked and complemented with genome analyses. We observed that ID50 varies in a continuous way by over 10 orders of magnitude. Low ID50 values are very strongly associated with the capacity of the bacteria to kill professional phagocytes or to survive in the intracellular milieu of these cells. Inversely, high ID50 values are associated with motile and fast-growing bacteria that use quorum-sensing based regulation of virulence factors expression. Infectious dose is not associated with genome size and shows insignificant phylogenetic inertia, in line with frequent virulence shifts associated with the horizontal gene transfer of a small number of virulence factors. Contrary to previous proposals, infectious dose shows little dependence on contact-dependent secretion systems and on the natural route of exposure. When all variables are combined, immune subversion and quorum-sensing are sufficient to explain two thirds of the variance in infectious dose. Our results show the key role of immune subversion in effective human infection by small bacterial populations. They also suggest that cooperative processes might be important for successful infection by bacteria with high ID50. Our results suggest that trade-offs between selection for population growth-related traits and selection for the ability to subvert the immune system shape bacterial infectiousness. Understanding these trade-offs provides guidelines to study the evolution of virulence and in particular the micro-evolutionary paths of emerging pathogens.
