Mutagenesis and modeling to predict structural and functional characteristics of the Staphylococcus aureus MepA multidrug efflux pump.

MepA is a multidrug and toxin extrusion (MATE) family protein and the only MATE protein encoded within the Staphylococcus aureus genome. Structural data for MATE proteins are limited to a single high-resolution example, NorM of Vibrio cholerae. Substitution mutations were created in MepA using gradient plates containing both a substrate and reserpine as an efflux pump inhibitor.

Expression of multidrug resistance efflux pump genes in clinical and environmental isolates of Staphylococcus aureus.

Increased expression of multidrug resistance efflux pump (MDR-EP) genes in clinical isolates of Staphylococcus aureus occurs frequently, but its temporal and geographic variability is unknown. Such strains may contaminate the hospital environment, posing an infection control problem. Nearly 700 clinical isolates from different geographic locales as well as 91 environmental isolates recovered from two Detroit hospitals were studied.

"Swimming in resistance": Co-colonization with carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii or Pseudomonas aeruginosa.

Background: Co-colonization of patients with carbapenem-resistant Enterobacteriaceae (CRE) and Acinetobacter baumannii (AB) or Pseudomonas aeruginosa (PA) is reported to be associated with increased antibiotic resistance and mortality.

Methods: CREs isolated between September 2008 and September 2009 were analyzed at Detroit Medical Center. Patients who had an additional isolation of AB or PA during the period spanning 7 days before to 7 days after CRE isolation were considered co-colonized.

The burden of multidrug-resistant organisms on tertiary hospitals posed by patients with recent stays in long-term acute care facilities.

Background: Long-term acute care (LTAC) facilities admit patients with complex, advanced disease states. Study aims were to determine the burden posed on hospitals associated with LTAC exposure and analyze the differences between "present on admission" (POA) multidrug-resistant (MDR), gram-negative organisms (GNO) and POA MDR gram-positive organisms (GPO).

Methods: A multicenter retrospective study was conducted in 13 hospitals from southeast Michigan, from September 1, 2008, to August 31, 2009.

Mechanisms of in-vitro-selected daptomycin-non-susceptibility in Staphylococcus aureus.

Daptomycin is highly active against Staphylococcus aureus, including multidrug-resistant strains and those with reduced susceptibility to vancomycin. However, daptomycin-non-susceptible (Dap(NS)) strains [minimum inhibitory concentration (MIC) >1mg/L] have been derived clinically and in vitro. The mechanism(s) by which this occurs is incompletely understood, but existing data indicate that it is multifactorial.

Outcomes and genetic relatedness of carbapenem-resistant enterobacteriaceae at Detroit medical center.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging in hospitals in the United States and are posing a significant threat. To better understand the transmission dynamics and the acquisition of resistant strains, a thorough analysis of epidemiologic and molecular characteristics was performed.

Methods: CRE isolated at Detroit Medical Center were analyzed from September 2008 to September 2009.

Evolution from a natural flavones nucleus to obtain 2-(4-Propoxyphenyl)quinoline derivatives as potent inhibitors of the S. aureus NorA efflux pump.

Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of substrate antimicrobial agents. Inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant phenotype.

Growing Old with HIV.

The intersection of chronic HIV infection, its treatment, and lifestyle with aging has become a topic of considerable fascination during this, the third decade of the AIDS epidemic. An understanding of the pathophysiology of this intersection may provide valuable insights into our general understanding of human aging. This review summarizes the results of recent publications that may have considerable impact on screening and management strategies in the aging HIV-infected population.

Discovery of novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus.

Four novel inhibitors of the NorA efflux pump of Staphylococcus aureus, discovered through a virtual screening process, are reported. The four compounds belong to different chemical classes and were tested for their in vitro ability to block the efflux of a well-known NorA substrate, as well as for their ability to potentiate the effect of ciprofloxacin (CPX) on several strains of S. aureus, including a NorA overexpressing strain.

Ethidium bromide MIC screening for enhanced efflux pump gene expression or efflux activity in Staphylococcus aureus.

Multidrug resistance efflux pumps contribute to antimicrobial and biocide resistance in Staphylococcus aureus. The detection of strains capable of efflux is time-consuming and labor-intensive using currently available techniques. A simple and inexpensive method to identify such strains is needed.