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Bisbiguanide

The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform

Roman Jerala – 1st expert on this subject based on the ideXlab platform

  • Alexidine and chlorhexidine bind to lipopolysaccharide and lipoteichoic acid and prevent cell activation by antibiotics
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Mateja Zorko, Roman Jerala

    Abstract:

    Objectives: Many antibiotics used to treat infections cause release of immunostimulatory cell wall components from bacteria. Therefore, a combination of antimicrobial and endotoxin-neutralizing activity is desired to prevent inflammation induced by destroyed bacteria. Chlorhexidine and alexidine are amphipathic Bisbiguanides and could neutralize bacterial membrane components as stimulators of Toll-like receptors (TLRs). Methods: Binding of chlorhexidine and alexidine to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) was determined by fluorescence displacement assay and isothermal calorimetric titration. Neutralization of the biological effect of LPS and LTA on TLR-activated cellular activation was determined by NF-kB reporter luciferase activation on cells transfected with specific TLRs and NO production of murine macrophages in the presence of isolated agonists and antibiotic-treated bacteria. Results: Alexidine and chlorhexidine bind not only to LPS but also to LTA from Gram-positive bacteria. Alexidine has a higher affinity than chlorhexidine for both compounds. Calorimetric titration shows an initial endothermic contribution indicating participation of hydrophobic interactions in LPS binding, while binding to LTA displayed initial exothermic contribution. Both compounds prevent cell activation of TLR4 and TLR2 by LPS and LTA, respectively. The addition of both compounds suppressed NO production by macrophages in the presence of bacteria treated with different types of antibiotics. Conclusions: Chlorhexidine and alexidine suppress bacterial membrane-induced cell activation at concentrations two orders of magnitude lower than that used in topical applications. Combining biocides with different types of antibiotics prevented macrophage activation in the presence of bacteria and demonstrated the potential of chlorhexidine and alexidine to suppress inflammatory responses caused by activation of TLRs.

  • Alexidine and chlorhexidine bind to lipopolysaccharide and lipoteichoic acid and prevent cell activation by antibiotics
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Mateja Zorko, Roman Jerala

    Abstract:

    OBJECTIVES: Many antibiotics used to treat infections cause release of immunostimulatory cell wall components from bacteria. Therefore, a combination of antimicrobial and endotoxin-neutralizing activity is desired to prevent inflammation induced by destroyed bacteria. Chlorhexidine and alexidine are amphipathic Bisbiguanides and could neutralize bacterial membrane components as stimulators of Toll-like receptors (TLRs).\n\nMETHODS: Binding of chlorhexidine and alexidine to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) was determined by fluorescence displacement assay and isothermal calorimetric titration. Neutralization of the biological effect of LPS and LTA on TLR-activated cellular activation was determined by NF-kappaB reporter luciferase activation on cells transfected with specific TLRs and NO production of murine macrophages in the presence of isolated agonists and antibiotic-treated bacteria.\n\nRESULTS: Alexidine and chlorhexidine bind not only to LPS but also to LTA from Gram-positive bacteria. Alexidine has a higher affinity than chlorhexidine for both compounds. Calorimetric titration shows an initial endothermic contribution indicating participation of hydrophobic interactions in LPS binding, while binding to LTA displayed initial exothermic contribution. Both compounds prevent cell activation of TLR4 and TLR2 by LPS and LTA, respectively. The addition of both compounds suppressed NO production by macrophages in the presence of bacteria treated with different types of antibiotics.\n\nCONCLUSIONS: Chlorhexidine and alexidine suppress bacterial membrane-induced cell activation at concentrations two orders of magnitude lower than that used in topical applications. Combining biocides with different types of antibiotics prevented macrophage activation in the presence of bacteria and demonstrated the potential of chlorhexidine and alexidine to suppress inflammatory responses caused by activation of TLRs.

Mateja Zorko – 2nd expert on this subject based on the ideXlab platform

  • Alexidine and chlorhexidine bind to lipopolysaccharide and lipoteichoic acid and prevent cell activation by antibiotics
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Mateja Zorko, Roman Jerala

    Abstract:

    Objectives: Many antibiotics used to treat infections cause release of immunostimulatory cell wall components from bacteria. Therefore, a combination of antimicrobial and endotoxin-neutralizing activity is desired to prevent inflammation induced by destroyed bacteria. Chlorhexidine and alexidine are amphipathic Bisbiguanides and could neutralize bacterial membrane components as stimulators of Toll-like receptors (TLRs). Methods: Binding of chlorhexidine and alexidine to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) was determined by fluorescence displacement assay and isothermal calorimetric titration. Neutralization of the biological effect of LPS and LTA on TLR-activated cellular activation was determined by NF-kB reporter luciferase activation on cells transfected with specific TLRs and NO production of murine macrophages in the presence of isolated agonists and antibiotic-treated bacteria. Results: Alexidine and chlorhexidine bind not only to LPS but also to LTA from Gram-positive bacteria. Alexidine has a higher affinity than chlorhexidine for both compounds. Calorimetric titration shows an initial endothermic contribution indicating participation of hydrophobic interactions in LPS binding, while binding to LTA displayed initial exothermic contribution. Both compounds prevent cell activation of TLR4 and TLR2 by LPS and LTA, respectively. The addition of both compounds suppressed NO production by macrophages in the presence of bacteria treated with different types of antibiotics. Conclusions: Chlorhexidine and alexidine suppress bacterial membrane-induced cell activation at concentrations two orders of magnitude lower than that used in topical applications. Combining biocides with different types of antibiotics prevented macrophage activation in the presence of bacteria and demonstrated the potential of chlorhexidine and alexidine to suppress inflammatory responses caused by activation of TLRs.

  • Alexidine and chlorhexidine bind to lipopolysaccharide and lipoteichoic acid and prevent cell activation by antibiotics
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Mateja Zorko, Roman Jerala

    Abstract:

    OBJECTIVES: Many antibiotics used to treat infections cause release of immunostimulatory cell wall components from bacteria. Therefore, a combination of antimicrobial and endotoxin-neutralizing activity is desired to prevent inflammation induced by destroyed bacteria. Chlorhexidine and alexidine are amphipathic Bisbiguanides and could neutralize bacterial membrane components as stimulators of Toll-like receptors (TLRs).\n\nMETHODS: Binding of chlorhexidine and alexidine to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) was determined by fluorescence displacement assay and isothermal calorimetric titration. Neutralization of the biological effect of LPS and LTA on TLR-activated cellular activation was determined by NF-kappaB reporter luciferase activation on cells transfected with specific TLRs and NO production of murine macrophages in the presence of isolated agonists and antibiotic-treated bacteria.\n\nRESULTS: Alexidine and chlorhexidine bind not only to LPS but also to LTA from Gram-positive bacteria. Alexidine has a higher affinity than chlorhexidine for both compounds. Calorimetric titration shows an initial endothermic contribution indicating participation of hydrophobic interactions in LPS binding, while binding to LTA displayed initial exothermic contribution. Both compounds prevent cell activation of TLR4 and TLR2 by LPS and LTA, respectively. The addition of both compounds suppressed NO production by macrophages in the presence of bacteria treated with different types of antibiotics.\n\nCONCLUSIONS: Chlorhexidine and alexidine suppress bacterial membrane-induced cell activation at concentrations two orders of magnitude lower than that used in topical applications. Combining biocides with different types of antibiotics prevented macrophage activation in the presence of bacteria and demonstrated the potential of chlorhexidine and alexidine to suppress inflammatory responses caused by activation of TLRs.

Kelli L. Palmer – 3rd expert on this subject based on the ideXlab platform

  • Reduced chlorhexidine and daptomycin susceptibility in vancomycin-resistant Enterococcus faecium after serial chlorhexidine exposure
    Antimicrobial Agents and Chemotherapy, 2017
    Co-Authors: Pooja Bhardwaj, Amrita Hans, Kinnari Ruikar, Ziqiang Guan, Kelli L. Palmer

    Abstract:

    Vancomycin-resistant Enterococcus faecium strains (VREfm) are critical public health concerns because they are among the leading causes of hospital-acquired bloodstream infections. Chlorhexidine (CHX) is a Bisbiguanide cationic antiseptic that is routinely used for patient bathing and other infection control practices. VREfm are likely frequently exposed to CHX; however, the long-term effects of CHX exposure have not been studied in enterococci. In this study, we serially exposed VREfm to increasing concentrations of CHX for a period of 21 days in two independent experimental evolution trials. Reduced CHX susceptibility emerged (4-fold shift in CHX MIC). Subpopulations with reduced daptomycin (DAP) susceptibility were detected, which were further analyzed by genome sequencing and lipidomic analysis. Across the trials, we identified adaptive changes in genes with predicted or experimentally confirmed roles in chlorhexidine susceptibility (efrE), global nutritional stress response (relA), nucleotide metabolism (cmk), phosphate acquisition (phoU), and glycolipid biosynthesis (bgsB), among others. Moreover, significant alterations in membrane phospholipids were identified for some populations with reduced DAP susceptibility. Our results are clinically significant because they identify a link between serial subinhibitory CHX exposure and reduced DAP susceptibility. In addition, the CHX-induced genetic and lipidomic changes described in this study offer new insights into the mechanisms underlying the emergence of antibiotic resistance in VREfm.

  • Reduced chlorhexidine and daptomycin susceptibility arises in vancomycin-resistant Enterococcus faecium after serial chlorhexidine exposure
    bioRxiv, 2017
    Co-Authors: Pooja Bhardwaj, Amrita Hans, Kinnari Ruikar, Ziqiang Guan, Kelli L. Palmer

    Abstract:

    Vancomycin-resistant Enterococcus faecium (VREfm) are critical public health concerns because they are among the leading causes of hospital-acquired bloodstream infections. Chlorhexidine (CHX) is a Bisbiguanide cationic antiseptic that is routinely used for patient bathing and other infection control practices. VREfm are likely frequently exposed to CHX; however, the long-term effects of CHX exposure have not been studied in enterococci. In this study, we serially exposed VREfm to increasing concentrations of CHX for a period of 21 days in two independent experimental evolution trials. Reduced CHX susceptibility emerged (4-fold shift in CHX MIC). Sub-populations with reduced daptomycin (DAP) susceptibility were detected, which were further analyzed by genome sequencing and lipidomic analysis. Across the trials, we identified adaptive changes in genes with predicted or experimentally confirmed roles in chlorhexidine susceptibility (efrE), global nutritional stress response (relA), nucleotide metabolism (cmk), phosphate acquisition (phoU), and glycolipid biosynthesis (bgsB), among others. Moreover, significant alterations in membrane phospholipids were identified. Our results are clinically significant because they identify a link between serial sub-inhibitory CHX exposure and reduced DAP susceptibility. In addition, the CHX-induced genetic and lipidomic changes described in this study offer new insights into the mechanisms underlying the emergence of antibiotic resistance in VREfm.

  • Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci
    Antimicrobial Agents and Chemotherapy, 2016
    Co-Authors: Pooja Bhardwaj, Elizabeth Ziegler, Kelli L. Palmer

    Abstract:

    ABSTRACT Chlorhexidine is a Bisbiguanide antiseptic used for infection control. Vancomycin-resistant E. faecium (VREfm) is among the leading causes of hospital-acquired infections. VREfm may be exposed to chlorhexidine at supra- and subinhibitory concentrations as a result of chlorhexidine bathing and chlorhexidine-impregnated central venous catheter use. We used RNA sequencing to investigate how VREfm responds to chlorhexidine gluconate exposure. Among the 35 genes upregulated ≥10-fold after 15 min of exposure to the MIC of chlorhexidine gluconate were those encoding VanA-type vancomycin resistance ( vanHAX ) and those associated with reduced daptomycin susceptibility ( liaXYZ ). We confirmed that vanA upregulation was not strain or species specific by querying other VanA-type VRE. VanB-type genes were not induced. The vanH promoter was found to be responsive to subinhibitory chlorhexidine gluconate in VREfm, as was production of the VanX protein. Using vanH reporter experiments with Bacillus subtilis and deletion analysis in VREfm, we found that this phenomenon is VanR dependent. Deletion of vanR did not result in increased chlorhexidine susceptibility, demonstrating that vanHAX induction is not protective against chlorhexidine. As expected, VanA-type VRE is more susceptible to ceftriaxone in the presence of sub-MIC chlorhexidine. Unexpectedly, VREfm is also more susceptible to vancomycin in the presence of subinhibitory chlorhexidine, suggesting that chlorhexidine-induced gene expression changes lead to additional alterations in cell wall synthesis. We conclude that chlorhexidine induces expression of VanA-type vancomycin resistance genes and genes associated with daptomycin nonsusceptibility. Overall, our results indicate that the impacts of subinhibitory chlorhexidine exposure on hospital-associated pathogens should be further investigated in laboratory studies.