Köhler Thilo, Buckling Angus, van Delden Christian
Department of Microbiology and Molecular Medicine and Service of Infectious Diseases, University Hospital Geneva, 1211 Geneva, Switzerland.
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6339-44. doi: 10.1073/pnas.0811741106. Epub 2009 Mar 30.
Bacteria communicate and cooperate to perform a wide range of social behaviors including production of extracellular products (public goods) that are crucial for growth and virulence. Their expression may be switched on by the detection of threshold densities of diffusible signals [Quorum-Sensing (QS)]. Studies using the opportunistic pathogen Pseudomonas aeruginosa suggest that QS "cheats"-individuals that don't respond to the QS signal, but are still able to use public goods produced by others-have a selective advantage in the presence of QS cooperators. It is, however, unclear whether this type of social exploitation is relevant in clinical contexts. Here, we report the evolutionary dynamics and virulence of P. aeruginosa populations during lung colonization of mechanically ventilated patients in the absence of antimicrobial treatments. We observed a large diversity of QS phenotypes among initial colonizing isolates. This diversity decreased over a matter of days, concomitant with a gradual increase in the proportion of QS cheating mutants (lasR mutants), which were found in 80% of the patients after 9 days of colonization. These mutants often evolved from initial wild-type genotypes. The fitness advantage of the lasR mutants is almost certainly due to social exploitation, because this advantage was only apparent in the presence of QS wild-type cells. Crucially, ventilator-associated pneumonia occurred significantly earlier in patients predominantly colonized by QS wild-type populations, highlighting the importance of QS in this clinical situation. These results demonstrate that social interactions can shape the short-term evolution and virulence of bacterial pathogens in humans, providing novel opportunities for therapy.
细菌通过交流与合作来执行广泛的社会行为，包括产生对生长和毒力至关重要的胞外产物（公共物品）。它们的表达可能通过检测可扩散信号的阈值密度[群体感应（QS）]来开启。利用机会致病菌铜绿假单胞菌进行的研究表明，QS“作弊者”——即那些对QS信号无反应，但仍能利用其他细菌产生的公共物品的个体——在有QS合作者存在的情况下具有选择优势。然而，这种类型的社会剥削在临床环境中是否相关尚不清楚。在此，我们报告了在没有抗菌治疗的情况下，机械通气患者肺部定植期间铜绿假单胞菌群体的进化动态和毒力。我们在初始定植菌株中观察到QS表型的巨大多样性。这种多样性在几天内就减少了，与此同时，QS作弊突变体（lasR突变体）的比例逐渐增加，在定植9天后，80%的患者中发现了这些突变体。这些突变体通常从初始的野生型基因型进化而来。lasR突变体的适应性优势几乎肯定是由于社会剥削，因为这种优势仅在有QS野生型细胞存在时才明显。至关重要的是，在主要由QS野生型群体定植的患者中，呼吸机相关性肺炎显著更早发生，突出了QS在这种临床情况下的重要性。这些结果表明，社会相互作用可以塑造人类细菌病原体的短期进化和毒力，为治疗提供了新的机会。
