Chronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa frequently fail to respond to antibiotic treatment, leading to significant patient morbidity and mortality. Currently, the impact of interspecies interaction on S. aureus antibiotic susceptibility remains poorly understood. In this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner and further identify 3 independent interactions responsible for antagonizing or potentiating antibiotic activity against S. aureus. We find that P. aeruginosa LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through respiratory inhibition and reduction of cellular ATP. We find that the production of each of these factors varies between clinical isolates and corresponds to the capacity of each isolate to alter S. aureus antibiotic susceptibility. Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn infection is potentiated by the presence of a LasA-producing P. aeruginosa population. These findings demonstrate that antibiotic susceptibility is complex and dependent not only upon the genotype of the pathogen being targeted, but also on interactions with other microorganisms in the infection environment. Consideration of these interactions will improve the treatment of polymicrobial infections.

金黄色葡萄球菌和铜绿假单胞菌的慢性合并感染常常无法对抗生素治疗产生反应，从而导致患者明显的发病率和死亡率。目前，种间相互作用对S的影响。金黄色葡萄球菌对抗生素的敏感性仍知之甚少。在这项研究中，我们利用P的面板。假单胞菌烧伤创面和囊性纤维化（CF）肺隔离证明P。铜绿假单胞菌变造小号。金黄色以可变的，应变依赖的方式对杀菌抗生素敏感，并进一步确定3种独立的相互作用，这些相互作用可拮抗或增强针对S的抗生素活性。金黄色的。我们发现，P。铜绿LasA内肽酶增强了S的裂解。金黄色葡萄球菌通过万古霉素，鼠李糖脂促进质子动力无关的妥布霉素摄取，和2-庚基-4-羟基喹Ñ氧化物（HQNO）诱导多药耐受性在小号。金黄色通过呼吸抑制和减少细胞ATP。我们发现，这些分离物的产生在临床分离株之间各不相同，并且与每个分离株改变S的能力相对应。金黄色葡萄球菌的药敏性。此外，我们表现出的万古霉素治疗小号。产LasA的P的存在增强了金黄色鼠烧伤感染。铜绿人口。这些发现表明，抗生素敏感性是复杂的，不仅取决于所靶向病原体的基因型，而且取决于与感染环境中其他微生物的相互作用。这些相互作用的考虑将改善多微生物感染的治疗。