A Multidisciplinary Approach toward Identification of Antibiotic Scaffolds for Acinetobacter baumannii

Abstract

Highlights d OM proteomics show that DcaP is the most abundant channel during rodent infection d The X-ray crystal structure of DcaP reveals a trimeric, porinlike structure d Dicarboxylic acids are transport substrates as shown by electrophysiology d Sulbactam, a clinically relevant b-lactamase inhibitor, permeates through DcaP

The characteristics of antibiotic resistance and phenotypes in 29 outer‐membrane protein mutant strains in Aeromonas hydrophila

“…Both proteins are controlled by the OmpR/EnvZ and CpxR/CpxA two‐component regulatory systems and display opposite behaviours when facing different kinds of antibiotics (Lin et al ., ). Therefore, it is a promising strategy to identify antibiotic scaffolds to overcome the OM permeability for the design of efficiently permeating antibiotics, such as sulbactam, a clinically relevant β‐lactamase inhibitor, that permeates through DcaP in Acinetobacter baumannii (Bhamidimarri et al ., ). Other typical OMPs are TolC in E .…”

“…Other typical OMPs are TolC in E . coli and its homologous protein in other species, such as AbuO in Acinetobacter baumannii , which can efflux antibiotics out of cells directly or by forming a complex with a periplasmic protein and an inner membrane protein, such as TolC‐AcrAB (Krishnamoorthy et al ., ; Srinivasan et al ., ; Bhamidimarri et al ., ). Besides these examples, several OMPs, such as LamB in E .…”

Elektrophysiologische Charakterisierung des Transports von Antibiotika durch äußere Membrankanäle in Gram‐negativen Bakterien in Gegenwart von Lipopolysacchariden

“…In früheren Arbeiten haben wir bereits den Transport durch E. coli ‐Kanäle auf Einzelkanalebene durch Rekonstitution in eine künstliche Lipiddoppelschicht charakterisiert. Um Informationen über den Transport zu erhalten, wurde der Ionenstrom in Abwesenheit oder in Gegenwart kleiner Moleküle gemessen . Eine ungelösste Frage war bislang der Beitrag der nativen Umgebung wie die LPS‐Schicht zur Permeabilität für kleine Moleküle durch die äußere Membran beiträgt.…”

Electrophysiological Characterization of Transport Across Outer‐Membrane Channels from Gram‐Negative Bacteria in Presence of Lipopolysaccharides

“…[20] Recent advancements in proteomics provide quantitative numbers of the membrane proteins distribution in bacteria under various growth conditions. [21] Previously, we characterized transport across an E. coli channel at a single protein level by reconstitution into an artificial lipid bilayer. To gain information on the mode of permeation, the ion current in absence and presence of small molecules was measured.…”

“…To gain information on the mode of permeation, the ion current in absence and presence of small molecules was measured. [21,22] The contribution of the native environment such as LPS layer on the channel and on the permeability for small molecules across the outer membrane remains an open question.…”