is an opportunistic bacteria and a major cause of nosocomial pneumonia. has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by that oxidizes polyunsaturated fatty acids. Based on previous biochemical studies, several biological roles of LoxA have been hypothesized, including interference of the host lipid signaling, and modulation of bacterial invasion properties. However, the contribution of LoxA to lung pathogenesis remained unclear. In this study, we used complementary and approaches, clinical strains of as well as lipidomics technology to investigate the role of LoxA in lung infection. We found that several clinical isolates express LoxA. When secreted in the lungs, LoxA processes a wide range of host polyunsaturated fatty acids, which further results in the production of bioactive lipid mediators (including lipoxin A ). LoxA also inhibits the expression of major chemokines (e.g., MIPs and KC) and the recruitment of key leukocytes. Remarkably, LoxA promotes persistence in lungs tissues. Hence, our study suggests that LoxA-dependent interference of the host lipid pathways may contribute to lung pathogenesis.