Disease relevance of PA5159

• Multidrug resistance among Gram-negative bacteria is conferred by three-component membrane pumps that expel diverse antibiotics from the cell [1].
• On the mechanism of substrate specificity by resistance nodulation division (RND)-type multidrug resistance pumps: the large periplasmic loops of MexD from Pseudomonas aeruginosa are involved in substrate recognition [2].
• Sixteen homologs of the mex-type multidrug resistance efflux pump in Bacteroides fragilis [3].
• A history of a prolonged hospital stay and exposure to antipseudomonal antibiotics predicts multidrug resistance among patients with P. aeruginosa respiratory tract infections at our institution [4].
• The emergence of multidrug resistance was observed for E. coli during patient stays in the ICU [5].

High impact information on PA5159

• Recent results indicate the existence of bacterial efflux systems of extremely broad substrate specificity, in many ways reminiscent of the multidrug resistance pump of mammalian cells [6].
• MexAB-OprM is a multidrug efflux system that contributes to intrinsic and acquired multidrug resistance in Pseudomonas aeruginosa, the latter as a result of mutational hyperexpression of the mexAB-oprM operon [7].
• Introduction of PA3719 into wild-type P. aeruginosa on a multicopy plasmid was, in fact, sufficient to promote elevated MexAB-OprM expression and multidrug resistance characteristic of a nalC strain [7].
• Mutation of the mexE gene eliminated the multidrug-resistance phenotype in an OprN-overexpressing strain, but did not affect the susceptibility profile of the wild-type strain [8].
• Clinical Prediction Tool To Identify Patients with Pseudomonas aeruginosa Respiratory Tract Infections at Greatest Risk for Multidrug Resistance [4].

Biological context of PA5159

• These results indicate that P. aeruginosa IMCJ2.S1 has developed multidrug resistance by acquiring resistance determinants, including a novel member of the aac(6')-I family and mutations in drug resistance genes [9].
• Sixteen homologs of multidrug resistance efflux pump operons of the resistance-nodulation-cell division (RND) family were found in the Bacteroides fragilis genome sequence by homology searches [3].
• Two new genes (mexXY) similar to mexAB, mexCD, and mexEF and mediating multidrug resistance were cloned from the chromosome of Pseudomonas aeruginosa [10].
• Some recently published works have analyzed the effect of the overproduction of MDR efflux pumps on bacterial virulence [11].
• The strain with one of those genotypes appeared to be endemic to the BWC and developed multidrug resistance (MDR) at the end of the study period, whereas the strain with the other genotype was antibiotic susceptible but resistant to silver sulfadiazine (SSD(r)) [12].

Anatomical context of PA5159

• These strains contained multidrug resistance determinants, were capable of invading epithelial cells and presented genes from the quorum-sensing and type III secretion systems [13].
• The MDR strain was found at a higher frequency in sputum samples than the SSD(r) strain, which showed a higher prevalence in burn wound samples, suggesting that anatomic habitat selection was associated with adaptive resistance to antimicrobial drugs [12].
• Current data on the prevalence of multidrug resistance among urinary tract isolates should be a consideration to change the current empiric treatment of urinary tract infections [14].

Associations of PA5159 with chemical compounds

• Rates of multidrug resistance (resistance to > or =3 of the following drugs: ceftazidime, ciprofloxacin, tobramycin, and imipenem) increased from 4% in 1993 to 14% in 2002 [15].
• PER-1 producers representative of the nine outbreaks exhibited a multidrug resistance (MDR) phenotype, including resistance to extended-spectrum cephalosporins, aztreonam, meropenem, aminoglycosides, and in most cases, imipenem and ciprofloxacin [16].
• These data are consistent with the hypothesis that incubation in the presence of tetracycline favours the emergence of MDR mutants in P. aeruginosa [17].

Regulatory relationships of PA5159

• Mutations in PA2491 (mexS) promote MexT-dependent mexEF-oprN expression and multidrug resistance in a clinical strain of Pseudomonas aeruginosa [18].

Other interactions of PA5159

• Mutations in PA3574 (nalD) lead to increased MexAB-OprM expression and multidrug resistance in laboratory and clinical isolates of Pseudomonas aeruginosa [19].
• Similarly, elimination of tonB from an nfxB strain only partially compromised MexCD-OprJ-mediated multidrug resistance [20].
• Mutations in mexR yield a multidrug resistance phenotype in nalB mutants of Pseudomonas aeruginosa as a result of derepression of the mexAB-oprM multidrug efflux operon [21].
• In general, the rate of multidrug resistance in the exoU positive cytotoxic and serotype E (O:11) strains was significantly higher than in exoS positive invasive strains (p < 0.01) [22].

Analytical, diagnostic and therapeutic context of PA5159

• Quantification of the prevalence and the common antimicrobial coresistance patterns of MDR gram-negative bacilli (MDR-GNB) isolates recovered from patients at hospital admission, as well as identification of patients with a high risk of harboring MDR-GNB, would have important implications for patient care [23].

References