RESUMEN
Pseudomonas aeruginosa (PA) is a Gram-negative, biofilm-forming bacterium and an opportunistic pathogen. The growing drug resistance of PA is a serious threat that necessitates the discovery of novel antibiotics, ideally with previously underexplored mechanisms of action. Due to their central role in cell metabolism, bacterial bioenergetic processes are of increasing interest as drug targets, especially with the success of the ATP synthase inhibitor bedaquiline to treat drug-resistant tuberculosis. Like Mycobacterium tuberculosis, PA requires F1Fo ATP synthase for growth, even under anaerobic conditions, making the PA ATP synthase an ideal drug target for the treatment of drug-resistant infection. In previous work, we conducted an initial screen for quinoline compounds that inhibit ATP synthesis activity in PA. In the present study, we report additional quinoline derivatives, including one with increased potency against PA ATP synthase in vitro and antibacterial activity against drug-resistant PA. Moreover, by expressing the PA ATP synthase in Escherichia coli, we show that mutations in the H+ binding site on the membrane-embedded rotor ring alter inhibition by the reported quinoline compounds. Identification of a potent inhibitor and its probable binding site on ATP synthase enables further development of promising quinoline derivatives into a viable treatment for drug-resistant PA infection.
Asunto(s)
Antiinfecciosos , Mycobacterium tuberculosis , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Antibacterianos/farmacología , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Adenosina TrifosfatoRESUMEN
BACKGROUND: How delegation of procedures varies among cosmetic specialties in the United States is not well described. OBJECTIVE: To better describe current practices in delegation of procedures to nonphysicians among physicians of different cosmetic specialties in the United States. METHODS: An Internet-based survey was administered to physician members of the American Society for Dermatologic Surgery (ASDS), the American Society for Aesthetic Plastic Surgery (ASAPS), and the American Society for Laser Medicine and Surgery (ASLMS). RESULTS: A total of 823 responses were collected. Two hundred ninety-one of the 521 dermatologists (55.9%) reported delegating cosmetic procedures compared with 223 of the 302 nondermatologists (73.8%) (p < .05). When delegation occurred, dermatologists were more likely than nondermatologists to delegate the following procedures to higher level non-physician providers (NPP): chemical peels, neuromodulator and filler injections, laser hair removal, pulsed dye laser, tattoo removal, intense pulsed light, nonablative fractional laser, and sclerotherapy. No difference in delegation rate was noted between dermatologists and non-dermatologist physicians with respect to microdermabrasion, ablative fractional laser, cryolipolysis, radiofrequency skin tightening, focused ultrasound skin tightening, and focused ultrasound fat reduction. CONCLUSION: Dermatologists delegate procedures to NPP less frequently than non-dermatologist physicians, and when they do, it is typically to higher level NPP.