PDF(Pubmed)
Abstract：
Bacterial infections are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus cause chronic co-infections, which are more problematic than mono-species infections. Understanding the mechanisms of their interactions is crucial for treating co-infections. Staphyloxanthin (STX), a yellow pigment synthesized by the S. aureus crt operon, promotes S. aureus resistance to oxidative stress and neutrophil-mediated killing. We found that STX production by S. aureus, either as surface-grown macrocolonies or planktonic cultures, was elevated when exposed to the P. aeruginosa exoproduct, 2-heptyl-4-hydroxyquinoline N-oxide (HQNO). This was observed with both mucoid and non-mucoid P. aeruginosa strains. The induction phenotype was found in a majority of P. aeruginosa and S. aureus clinical isolates examined. When subjected to hydrogen peroxide or human neutrophils, P. aeruginosa survival was significantly higher when mixed with wild-type (WT) S. aureus, compared to P. aeruginosa alone or with an S. aureus crt mutant deficient in STX production. In a murine wound model, co-infection with WT S. aureus, but not the STX-deficient mutant, enhanced P. aeruginosa burden and disease compared to mono-infection. In conclusion, we identified a role for P. aeruginosa HQNO mediating polymicrobial interactions with S. aureus by inducing STX production, which consequently promotes resistance to the innate immune effectors H2O2 and neutrophils. These results further our understanding of how different bacterial species cooperatively cause co-infections.
摘要：
细菌感染通常是多微生物的。铜绿假单胞菌和金黄色葡萄球菌引起慢性共感染，比单一物种感染更有问题。了解它们相互作用的机制对于治疗共感染至关重要。葡萄黄质(STX),金黄色葡萄球菌crt操纵子合成的黄色色素，促进金黄色葡萄球菌对氧化应激和中性粒细胞介导的杀伤的抗性。我们发现金黄色葡萄球菌产生STX，作为表面生长的大型菌落或浮游文化，当暴露于铜绿假单胞菌外切产品时，2-庚基-4-羟基喹啉N-氧化物(HQNO)。这在粘液和非粘液铜绿假单胞菌菌株中都观察到。在所检查的大多数铜绿假单胞菌和金黄色葡萄球菌临床分离株中发现了诱导表型。当接触过氧化氢或人类嗜中性粒细胞时，当与野生型（WT）金黄色葡萄球菌混合时，铜绿假单胞菌的存活率显着提高，与单独的铜绿假单胞菌或具有STX生产缺陷的金黄色葡萄球菌crt突变体相比。在一个鼠类伤口模型中,与WT金黄色葡萄球菌共感染，但不是STX缺陷型突变体,与单一感染相比，铜绿假单胞菌的负担和疾病增加。总之,我们确定了铜绿假单胞菌HQNO通过诱导STX产生介导多微生物与金黄色葡萄球菌相互作用的作用，从而促进对先天免疫效应物H2O2和中性粒细胞的抗性。这些结果进一步加深了我们对不同细菌物种如何合作导致共同感染的理解。
