Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii.
LpxC inhibitors have generally shown poor in vitro activity against Acinetobacter baumannii We show that the LpxC inhibitor PF-5081090 inhibits lipid A biosynthesis, as determined by silver staining and measurements of endotoxin levels, and significantly increases cell permeability. The presence of PF-5081090 at 32 mg/liter increased susceptibility to rifampin, vancomycin, azithromycin, imipenem, and amikacin but had no effect on susceptibility to ciprofloxacin and tigecycline. Potentiating existing antibiotics with LpxC inhibitors may represent an alternative treatment strategy for multidrug-resistant A. baumannii.
Unit of Infectious Diseases, Microbiology, and Preventive Medicine and Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain.
Meritxell
M
García-Quintanilla
Unit of Infectious Diseases, Microbiology, and Preventive Medicine and Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain.
José M
JM
Caro-Vega
Unit of Infectious Diseases, Microbiology, and Preventive Medicine and Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain.
Marina R
MR
Pulido
Unit of Infectious Diseases, Microbiology, and Preventive Medicine and Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain.
Patricia
P
Moreno-Martínez
Unit of Infectious Diseases, Microbiology, and Preventive Medicine and Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain.
Jerónimo
J
Pachón
Unit of Infectious Diseases, Microbiology, and Preventive Medicine and Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain mcconnell.mike75@gmail.com.
Michael J
MJ
McConnell
D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000378:metabolism*; D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015780:Carbapenems / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D015378:Imipenem / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D000078304:Tigecycline; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D014640:Vancomycin; D000078304:Tigecycline; D015378:Imipenem; D017963:Azithromycin; D000583:Amikacin; D000581:Amidohydrolases; D008911:Minocycline; D012293:Rifampin