High-level beta-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment

Giwercman, Birgit; Meyer, Christian; Lambert, Peter A.; Reinert, Christiane; Høiby, Niels

doi:10.1128/aac.36.1.71

Cited by 65 publications

(44 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study has clearly demonstrated highlevel beta-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment. 27 This study further propose and support the hypothesis that b-lactamase production is an important in vivo resistance mechanism in infected patients which could subsequently lead to more severe inflammation and scaring formation. Aspartoacylase-3 reported to localize to the cytoplasm of S2 and S3 proximal tubules and to the apical domain of S1 proximal tubules 28 and may function as an hepatitis C virus (HCV) core binding protein which may play a role in the development of HCV-associated diseases.…”

Section: Discussionsupporting

confidence: 66%

Potential biomarkers associated with diabetic glomerulopathy through proteomics

Hsu

Lei

et al. 2015

Renal Failure

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is characterized by the development of progressive glomerulosclerotic lesions gradually leading to an increasing loss of functioning kidney parenchyma. Relatively little proteomic research of isolated glomeruli of experimental animal models has been done so far. Isolated glomerular proteomics is an innovative tool that potentially detects simultaneous expressions of glomeruli in diabetic pathological contexts. We compared the isolated glomerular profiles of rats with and without diabetes. The proteins in the aliquots of glomeruli were subjected to two-dimensional gel electrophoresis. The protein spots were matched and quantified using an imaging analysis system. The peptide mass fingerprints were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and a bioinformation search. We found that diabetes increased collagen type I and collagen type IV levels in diabetic glomeruli when compared to normal control group using Dynabeads. We found that rats with diabetes had significantly higher abundance of the Protein disulfide isomerase associated 3, Aspartoacylase-3,3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase, Lactamase beta 2 and Agmat protein. However, diabetic glomeruli in rats had significantly lower levels of the Regucalcin, rCG52140, Aldo-keto reductase family 1, Peroxiredoxin 1, and L-arginine: glycine amidinotransferase. These proteins of interest were reported to modulate disturbances in the homeostasis of endoplasmic reticulum stress, disturbance of inflammatory and fibrinogenic activities, impairing endothelial function, and dysregulation in the antioxidation capacity/oxidative stress in several tissue types under pathological contexts. Taken together, our high-throughput isolated glomerular proteomic findings indicated that multiple pathological reactions presumably occurred in DN.

show abstract

Section: Discussionsupporting

confidence: 66%

Potential biomarkers associated with diabetic glomerulopathy through proteomics

Hsu

Lei

et al. 2015

Renal Failure

View full text Add to dashboard Cite

show abstract

“…Preexisting subpopulations with stable, partially derepressed AmpC may thus rapidly expand under treatment with agents such as ceftazidime, piperacillin, or imipenem (17). Partial release of their ␤-lactamase content in sputum samples could contribute to antibiotic inactivation in situ (18). Whether these partially derepressed mutants would provide more susceptible bacterial populations with efficient protection against ␤-lactams is unclear.…”

Section: Discussionmentioning

confidence: 99%

Efflux Unbalance in Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients

Vettoretti

Plésiat

Muller

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Retrospective analysis of 189 nonredundant strains of Pseudomonas aeruginosa sequentially recovered from the sputum samples of 46 cystic fibrosis (CF) patients over a 10-year period (1998 to 2007) revealed that 53 out of 189 (28%) samples were hypersusceptible to the ␤-lactam antibiotic ticarcillin (MIC < 4 g/ml) (phenotype dubbed Tic hs ). As evidenced by trans-complementation and gene inactivation experiments, the mutational upregulation of the efflux system MexXY was responsible for various degrees of resistance to aminoglycosides in a selection of 11 genotypically distinct strains (gentamicin MICs from 2 to 64 g/ml). By demonstrating for the first time that the MexXY pump may evolve in CF strains, we found that a mutation leading to an F1018L change in the resistance-nodulation-cell division (RND) transporter MexY was able to increase pump-promoted resistance to aminoglycosides, cefepime, and fluoroquinolones twofold. The inactivation of the mexB gene (which codes for the RND transporter MexB) in the 11 selected strains showed that the Tic hs phenotype was due to a mutational or functional loss of function of MexAB-OprM, the multidrug efflux system known to contribute to the natural resistance of P. aeruginosa to ␤-lactams (e.g., ticarcillin and aztreonam), fluoroquinolones, tetracycline, and novobiocin. Two of the selected strains synthesized abnormally low amounts of the MexB protein, and 3 of 11 strains expressed truncated MexB (n ‫؍‬ 2) or MexA (n ‫؍‬ 1) polypeptide as a result of mutations in the corresponding genes, while 7 of 11 strains produced wild-type though nonfunctional MexAB-OprM pumps at levels similar to or even higher than that of reference strain PAO1. Overall, our data indicate that while MexXY is necessary for P. aeruginosa to adapt to the hostile environment of the CF lung, the MexAB-OprM pump is dispensable and tends to be lost or inactivated in subpopulations of P. aeruginosa.

show abstract

“…Some data indeed suggest that in nfxB mutants, the enzyme AmpC leaks out of the cells and concentrates in the surrounding milieu rather than in the periplasm, thus generating whole protection for cells of the biofilm (472). This may be relevant in vivo, as important extracellular AmpC activities have been measured in the sputa of cystic fibrosis patients (473). Whereas the mexXY genes (and their products) are expressed at similar levels in nfxB mutants and wild-type strains, MexCD-OprJ appears to compromise the MexXY/OprM(OprA) drug transport activity and associated resistance to aminoglycosides by downmodulating the production of the protein OprM (472).…”

Section: Pseudomonas Aeruginosamentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

View full text Add to dashboard Cite

SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

show abstract

High-level beta-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment

Cited by 65 publications

References 14 publications

Potential biomarkers associated with diabetic glomerulopathy through proteomics

Potential biomarkers associated with diabetic glomerulopathy through proteomics

Efflux Unbalance in Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

Contact Info

Product

Resources

About