Unité de Recherche en Maladies Infectieuses Tropical Emergentes (URMITE), CNRS-IRD UMR 6236-198, Université de la Méditerranée Marseille, France.
Front Cell Infect Microbiol. 2011 Oct 25;1:7. doi: 10.3389/fcimb.2011.00007. eCollection 2011.
The term toxin was introduced by Roux and Yersin and describes macromolecular substances that, when produced during infection or when introduced parenterally or orally, cause an impairment of physiological functions that lead to disease or to the death of the infected organism. Long after the discovery of toxins, early genetic studies on bacterial virulence demonstrated that removing a certain number of genes from pathogenic bacteria decreases their capacity to infect hosts. Each of the removed factors was therefore referred to as a "virulence factor," and it was speculated that non-pathogenic bacteria lack such supplementary factors. However, many recent comparative studies demonstrate that the specialization of bacteria to eukaryotic hosts is associated with massive gene loss. We recently demonstrated that the only features that seem to characterize 12 epidemic bacteria are toxin-antitoxin (TA) modules, which are addiction molecules in host bacteria. In this study, we investigated if protein toxins are indeed the only molecules specific to pathogenic bacteria by comparing 14 epidemic bacterial killers ("bad bugs") with their 14 closest non-epidemic relatives ("controls"). We found protein toxins in significantly more elevated numbers in all of the "bad bugs." For the first time, statistical principal components analysis, including genome size, GC%, TA modules, restriction enzymes, and toxins, revealed that toxins are the only proteins other than TA modules that are correlated with the pathogenic character of bacteria. Moreover, intracellular toxins appear to be more correlated with the pathogenic character of bacteria than secreted toxins. In conclusion, we hypothesize that the only truly identifiable phenomena, witnessing the convergent evolution of the most pathogenic bacteria for humans are the loss of metabolic activities, i.e., the outcome of the loss of regulatory and transcription factors and the presence of protein toxins, alone, or coupled as TA modules.
术语“毒素”由 Roux 和 Yersin 引入，用于描述大分子物质，当这些物质在感染期间产生或通过肠外或口服途径引入时，会导致生理功能受损，从而导致疾病或感染生物体死亡。在发现毒素很久之后，早期关于细菌毒力的遗传研究表明，从致病性细菌中去除一定数量的基因会降低其感染宿主的能力。因此，每个被去除的因素都被称为“毒力因子”，并且推测非致病性细菌缺乏这种补充因子。然而，许多最近的比较研究表明，细菌对真核宿主的专业化与大量基因丢失有关。我们最近表明，似乎唯一能将 12 种流行细菌特征化的特征是毒素-抗毒素 (TA) 模块，这些模块是宿主细菌中的成瘾分子。在这项研究中，我们通过比较 14 种流行的细菌杀手（“坏细菌”）与其 14 种最接近的非流行亲缘体（“对照”），来调查蛋白质毒素是否确实是仅存在于致病性细菌中的分子。我们发现所有“坏细菌”中的蛋白质毒素数量都明显更高。首次通过包括基因组大小、GC%、TA 模块、限制酶和毒素在内的统计主成分分析，揭示了毒素是除 TA 模块之外唯一与细菌致病性相关的蛋白质。此外，细胞内毒素似乎比分泌毒素更与细菌的致病性相关。总之，我们假设唯一可以真正识别的现象，见证了对人类最具致病性的细菌的趋同进化，是代谢活性的丧失，即调节因子和转录因子的丧失以及单独存在或作为 TA 模块存在的蛋白质毒素的结果。
