了解食源性病原体在整个食品生产链中的进化动态至关重要。在这项研究中,我们发现,鼠伤寒沙门氏菌在反复暴露于热休克时可以容易且可重复地获得大大提高的抗热休克能力。反直觉,这种抗热休克能力的提高总是通过dnaJ基因的功能丧失突变获得的,编码一种热休克蛋白,该蛋白充当DnaK的分子共伴侣,并使其在蛋白质折叠和解聚中发挥作用。作为一种权衡,然而,获得耐热冲击性不可避免地导致在37°C和更高温度下的生长减弱。有趣的是,DnaJ的丢失也下调了主毒力调节剂HilD的活性,从而降低群体中表达毒力的细胞的分数并减弱小鼠的毒力。通过将耐热冲击性演化与HilD活动的衰减联系起来,我们的结果证实了鼠伤寒沙门氏菌的抗逆性和毒力之间的复杂相互作用。
目的:细菌病原体如鼠伤寒沙门氏菌具有应激反应和毒力特征,以便在各种复杂的不适宜环境中导航,从食品加工厂到动物宿主的胃肠道。在这种情况下,然而,对一种环境的适应是否以及如何会阻碍另一种环境的健康,这仍然是模糊的。在这项研究中,我们发现严重的热应激与直觉相反,但总是,导致了对DnaJ热休克蛋白活性受损的鼠伤寒沙门氏菌突变体的选择。虽然这些突变体获得了大量增加的耐热性,他们的毒力大大减弱。我们的观察,因此,揭示了细菌病原体应激反应和毒力特征的最佳调整之间的微妙平衡。
Understanding the evolutionary dynamics of foodborne pathogens throughout our food production chain is of utmost importance. In this study, we reveal that Salmonella Typhimurium can readily and reproducibly acquire vastly increased heat shock resistance upon repeated exposure to heat shock. Counterintuitively, this boost in heat shock resistance was invariantly acquired through loss-of-function mutations in the dnaJ gene, encoding a heat shock protein that acts as a molecular co-chaperone of DnaK and enables its role in protein folding and disaggregation. As a trade-off, however, the acquisition of heat shock resistance inevitably led to attenuated growth at 37°C and higher temperatures. Interestingly, loss of DnaJ also downregulated the activity of the master virulence regulator HilD, thereby lowering the fraction of virulence-expressing cells within the population and attenuating virulence in mice. By connecting heat shock resistance evolution to attenuation of HilD activity, our results confirm the complex interplay between stress resistance and virulence in Salmonella Typhimurium.
OBJECTIVE: Bacterial pathogens such as Salmonella Typhimurium are equipped with both stress response and virulence features in order to navigate across a variety of complex inhospitable environments that range from food-processing plants up to the gastrointestinal tract of its animal host. In this context, however, it remains obscure whether and how adaptation to one environment would obstruct fitness in another. In this study, we reveal that severe heat stress counterintuitively, but invariantly, led to the selection of S. Typhimurium mutants that are compromised in the activity of the DnaJ heat shock protein. While these mutants obtained massively increased heat resistance, their virulence became greatly attenuated. Our observations, therefore, reveal a delicate balance between optimal tuning of stress response and virulence features in bacterial pathogens.