Synopsis Everyday, normal breathing deposits numerous microorganisms on the surfactant membrane that lines the air-exchanging surfaces of the lung. Surfactant protein SP-A, a component of the surfactant membrane, helps to maintain the lung in a germ-free state by aggregating inhaled microorganisms and facilitating their ingestion by immune cells, and by increasing the permeability of their cell membranes. However, the bacterial pathogen Pseudomonas aeruginosa is resistant to SP-A-mediated membrane disruption. Using a genetic tool called comparative signature-tagged mutagenesis, the authors have identified two P. aeruginosa genes, pch and ptsP, that are required to resist SP-A-mediated membrane permeabilization. Molecular analyses indicate that the pch gene encodes an enzyme that synthesizes salicylate, a compound utilized by bacteria to acquire essential metal ions. The ptsP gene encodes an enzyme called phosphoenolpyruvate-protein-phosphotransferase. The loss of salicylate and phosphoenolpyruvate-protein-phosphotransferase weakens the P. aeruginosa cell membrane, which allows SP-A to poke holes on the membrane and kill the bacteria. This is the first known report of the roles played by salicylate and phosphoenolpyruvate-protein-phosphotransferase in maintenance of bacterial membrane, and consequently, protecting bacteria from killing by SP-A, through disruption of membrane integrity.