Abstract：
Pseudomonas aeruginosa, a Gram-negative bacterium that causes severe hospital acquired infections poses threat by its ability for adaptation to various growth modes and environmental conditions and by its intrinsic resistance to antibiotics. The latter is mainly due to the outer membrane (OM) asymmetry which is maintained by the Mla pathway resulting in the retrograde transport of glycerophospholipids from the OM to the inner membrane. It comprises six Mla proteins, including MlaA, an OM lipoprotein involved in the removal of glycerophospholipids mislocalized at the outer leaflet of OM. To investigate the role of P. aeruginosa OM asymmetry especially MlaA, this study investigated the effect of mlaA deletion on (i) the susceptibility to antibiotics, (ii) the secretion of virulence factors, the motility, biofilm formation, and (iii) the inflammatory response. mlaA deletion in P. aeruginosa ATCC27853 results in phenotypic changes including, an increase in fluoroquinolones susceptibility and in PQS (Pseudomonas Quinolone Signal) and TNF-α release and a decrease in rhamnolipids secretion, motility and biofilm formation. Investigating how the mlaA knockout impacts on antibiotic susceptibility, bacterial virulence and innate immune response will help to elucidate the biological significance of the Mla system and contribute to the understanding of MlaA in P. aeruginosa OM asymmetry.
摘要：
铜绿假单胞菌,导致严重医院获得性感染的革兰氏阴性细菌由于其适应各种生长模式和环境条件的能力以及其对抗生素的内在抗性而构成威胁。后者主要是由于Mla途径维持的外膜（OM）不对称性，导致甘油磷脂从OM向内膜的逆行转运。它包含六种Mla蛋白，包括Mlaa,一种OM脂蛋白，涉及去除OM外小叶上的甘油磷脂。为了研究铜绿假单胞菌OM不对称特别是MlaA的作用，这项研究调查了mlaA缺失对(i)抗生素敏感性的影响，(ii)分泌毒力因子，运动性，生物膜的形成，和(iii)炎症反应。铜绿假单胞菌ATCC27853中的mlaA缺失导致表型变化，包括，氟喹诺酮类药物敏感性增加，PQS（假单胞菌喹诺酮类药物信号）和TNF-α释放增加，鼠李糖脂分泌减少，运动性和生物膜形成。调查mlaA基因敲除对抗生素敏感性的影响，细菌毒力和先天免疫反应将有助于阐明Mla系统的生物学意义，并有助于理解MlaA在铜绿假单胞菌OM不对称中的作用。
