Structure-activity relationships of actively FhuE transported rifabutin derivatives with potent activity against Acinetobacter baumannii.

Hospital-acquired infections are on the rise and represent both, a clinical and financial burden. With resistance emerging and an ever-dwindling armamentarium at hand, infections caused by Acinetobacter baumannii are particularly problematic, since these bacteria have a high level of resistance and resilience to traditional and even last-resort antibiotics. The antibiotic rifabutin was recently found to show potent in vitro and in vivo activity against extensively drug resistant A.

Targeting virulence regulation to disarm pathogenesis.

The development of anti-virulence drug therapy against infections would provide an alternative to traditional antibacterial therapy that are increasingly failing. Here, we demonstrate that the OmpR transcriptional regulator plays a pivotal role in the pathogenesis of diverse clinical strains in multiple murine and invertebrate infection models. We identified OmpR-regulated genes using RNA sequencing and further validated two genes whose expression can be used as robust biomarker to quantify OmpR inhibition in .

Design and synthesis of water-soluble prodrugs of rifabutin for intraveneous administration.

Acinetobacter baumannii is a gram-negative bacterium causing severe hospital-acquired infections such as bloodstream infections or pneumonia. Moreover, multidrug resistant A. baumannii becomes prevalent in many hospitals.

In vitro activity of rifabutin against 293 contemporary carbapenem-resistant Acinetobacter baumannii clinical isolates and characterization of rifabutin mode of action and resistance mechanisms.

Background: Rifabutin, an oral drug approved to treat Mycobacterium avium infections, demonstrated potent activity against Acinetobacter baumannii in nutrient-limited medium enabled by rifabutin cellular uptake through the siderophore receptor FhuE.

Objectives: To determine rifabutin in vitro activity and resistance mechanisms in a large panel of A. baumannii isolates.

Dissecting Colistin Resistance Mechanisms in Extensively Drug-Resistant Acinetobacter baumannii Clinical Isolates.

Nosocomial infections with are a global problem in intensive care units with high mortality rates. Increasing resistance to first- and second-line antibiotics has forced the use of colistin as last-resort treatment, and increasing development of colistin resistance in has been reported. We evaluated the transcriptional regulator PmrA as potential drug target to restore colistin efficacy in Deletion of restored colistin susceptibility in 10 of the 12 extensively drug-resistant clinical isolates studied, indicating the importance of PmrA in the drug resistance phenotype.