Disease relevance of SAB2047c

• Multidrug resistance proteins QacA and QacB from Staphylococcus aureus: membrane topology and identification of residues involved in substrate specificity [1].
• Emr, an Escherichia coli locus for multidrug resistance [2].
• In Gram-negative bacteria, a subset of inner membrane proteins in the major facilitator superfamily (MFS) acts as efflux pumps to decrease the intracellular concentrations of multiple toxic substrates and confers multidrug resistance [3].
• In this report, we show that BIBW22 BS, a phenylpteridine analog, reverses the MDR phenotype of CEM human lymphoma cells in a dose-dependent fashion [4].
• We used MDR-deficient mutants of Staphylococcus aureus (NorA), Escherichia coli (TolC), and Pseudomonas aeruginosa (MexAB) and found 2 to 4 logs more killing than seen with wild-type strains by use of three different phenothiazinium PSs and red light [5].

High impact information on SAB2047c

• MDR-dependent efflux of ethidium bromide and berberine from S. aureus cells was completely inhibited by 5'-MHC [6].
• Sensitivity to quinolones and to amphipathic cations (norfloxacin, benzalkonium chloride, cetrimide, pentamidine, etc.) was increased 5- to 30-fold in a Staphylococcus aureus mutant with a disrupted chromosomal copy of the NorA MDR [7].
• Crystal structure analysis showed that the CGL2612 protein exhibits significant structural similarity to the multidrug resistance (MDR)-related transcription factor QacR from Staphylococcus aureus, despite poor amino acid sequence similarity between these proteins [8].
• Current concerns with gram-positive pathogens are increasing multidrug resistance in methicillin-resistant Staphylococcus aureus, enterococci, and coagulase-negative staphylococci, and increasing incidence of penicillin-resistant Streptococcus pneumoniae [9].
• Drug binding studies showed that membranes from MDR cells bound more BIBW22 BS than parental drug-sensitive cells, and this binding was inhibited with vinblastine and, to a lesser extent, with uridine [4].

Chemical compound and disease context of SAB2047c

• Epicatechin gallate (1) and epigallocatechin gallate (2) were evaluated for their antibacterial and efflux inhibitory activity against a wild-type and three multidrug-resistant (MDR) strains of Staphylococcus aureus [10].
• Catechin gallates inhibit multidrug resistance (MDR) in Staphylococcus aureus [10].

Biological context of SAB2047c

• Flavonolignan and flavone inhibitors of a Staphylococcus aureus multidrug resistance pump: structure-activity relationships [11].
• Genome sequencing data suggest that Staphylococcus aureus may possess numerous chromosomally encoded MDR efflux pumps, most of which have not been characterized [12].
• Two independently derived S. aureus mutants having efflux-related MDR phenotypes were studied using microarray technology and a marked overexpression of an open reading frame (ORF; mepA) encoding a protein homologous with MATE family proteins was observed in both [13].
• For S. aureus SA-1199B, which overexpresses the NorA MDR efflux pump, and for two additional strains of S. aureus having non-NorA-mediated MDR phenotypes, the 50% inhibitory concentration (IC(50)) for ethidium efflux for all tested compounds was between 4 and 15% of their respective MICs [12].
• The staphylococcal qacB-encoding multidrug resistance plasmid pSK156, isolated from a clinical strain dating from 1951, was characterized [14].

Associations of SAB2047c with chemical compounds

• [125I]NAPS photolabeling of P-gp was preferentially competed by MDR-related drugs, with vinblastine > VCR > colchicine > doxorubicin > actinomycin D [15].
• Inhibition of antibiotic efflux in bacteria by the novel multidrug resistance inhibitors biricodar (VX-710) and timcodar (VX-853) [16].
• The inhibitory effects of selected phenothiazines and two geometric stereoisomers of the thioxanthene flupentixol were studied using strains of S. aureus possessing unique efflux-related MDR phenotypes [12].
• The primary purpose of the multicenter international study "RESIST" was to obtain an update on the degree of multidrug resistance among methicillin-resistant staphylococci collected from a geographically diverse sample [17].
• These phenotypes were also the most common among inpatient MRSA (n = 946), but multidrug resistance to erythromycin, clindamycin, and levofloxacin (43.7%) was most common [18].

Analytical, diagnostic and therapeutic context of SAB2047c

• Patterns of multidrug resistance among methicillin-resistant hospital isolates of coagulase-positive and coagulase-negative staphylococci collected in the international multicenter study RESIST in 1997 and 1998 [17].

References