The adaptation mechanism of Pseudomonas aeruginosa ATCC 10145 to quaternary ammonium compounds (QACs) was investigated. A P. aeruginosa strain with adapted resistance to QACs was developed by a standard broth dilution method. It was revealed that P. aeruginosa exhibited remarkable resistance to N-dodecylpyridinium iodide (P-12), whose structure is similar to that of a common disinfectant, cetylpyridinium chloride. Adapted resistance to benzalkonium chloride (BAC), which is commonly used as a disinfectant, was also observed in P. aeruginosa. Moreover, the P-12-resistant strain exhibited cross-resistance to BAC. Analysis of the outer membrane protein of the P-12-resistant strain by two-dimensional polyacrylamide gel electrophoresis showed a significant increase in the level of expression of a protein (named OprR) whose molecular mass was approximately 26 kDa. The actual function of OprR is not yet clear; however, OprR was expected to be an outer membrane-associated protein with homology to lipoproteins of other bacterial species, according to a search of the National Center for Biotechnology Information website with the BLAST program by use of the Nterminal sequence of OprR. A correlation between the level of expression of OprR and the level of resistance of P. aeruginosa to QACs was observed by using a PA2800 gene knockout mutant derived from the P-12-resistant strain. The knockout mutant recovered susceptibility not only to P-12 but also to BAC. These results suggested that OprR significantly participated in the adaptation of P. aeruginosa to QACs, such as P-12 and BAC.In recent years, disinfectants have been used indiscriminately because of our increased desire for cleanliness. The boom in "antibacterial" products has accelerated these trends. Furthermore, the indiscriminate use of disinfectants provides a hotbed for the adaptation of bacteria to those products and increases the spread of resistant bacteria. Similarly, as with many other disinfectants, bacterial resistance to quaternary ammonium compounds (QACs) has recently caused serious problems. Pseudomonas aeruginosa isolates have frequently been found to be resistant to QACs (3,4,5,9,11,19,27,28). P. aeruginosa is ubiquitous in the environment and shows intrinsic resistance to high levels of QACs (18). The intrinsic resistance of this organism seems to be due to the cell wall and the cell membrane; for example, antimicrobials cannot easily access their sites of action because of the lower level of permeability of the outer membrane (14), and efflux pumps cause enhanced levels of efflux of antimicrobials (8). Moreover, since the species has a broad range of growth temperatures and possesses sturdy metabolism pathways, in addition to high levels of resistance to antibiotics and disinfectants, it is difficult to control with antimicrobials and has been shown to be an opportunistic pathogen and an infectious pathogen in hospitals. The phenotypic changes in P. aeruginosa cells corresponding to the increased levels of resistance to QACs have been investigated a...