Mode of action of dysgalacticin: a large heat-labile bacteriocin
Autor: | Pearl M. Swe, Ralph W. Jack, Gregory M. Cook, John R. Tagg |
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Rok vydání: | 2009 |
Předmět: |
Microbiology (medical)
Cell Membrane Permeability Streptococcus pyogenes Microbial Sensitivity Tests Biology medicine.disease_cause Models Biological Cell membrane Bacterial Proteins Bacteriocins Serine medicine Extracellular Pharmacology (medical) Phosphoenolpyruvate Sugar Phosphotransferase System Mode of action Pharmacology Membrane potential Microbial Viability Glucose transporter Anti-Bacterial Agents Phosphotransferases (Alcohol Group Acceptor) Glucose Infectious Diseases medicine.anatomical_structure Mechanism of action Biochemistry Carbohydrate Metabolism medicine.symptom Intracellular |
Zdroj: | Journal of Antimicrobial Chemotherapy. 63:679-686 |
ISSN: | 1460-2091 0305-7453 |
DOI: | 10.1093/jac/dkn552 |
Popis: | Objectives: The mode of action of dysgalacticin, a large (21.5 kDa), heat-labile bacteriocin that is active against the human pathogen Streptococcus pyogenes, was investigated. Methods: We used recombinant dysgalacticin to determine its mode of action against S. pyogenes. Antimicrobial activity of dysgalacticin was determined by MIC assays and viability counts. The extracellular pH of glucose-energized S. pyogenes cell suspensions was measured to determine the influence of dysgalacticin on glucose fermentation. To examine the effect of dysgalacticin on glucose transport, uptake of [ 14 C]glucose and the non-metabolizable analogue [ 3 H]2-deoxyglucose (2DG) was measured. Furthermore, the effect of dysgalacticin on membrane integrity, intracellular potassium concentration, membrane potential and [ 14 C]serine uptake was determined. Results: Dysgalacticin was bactericidal towards S. pyogenes and inhibited glucose fermentation by non-growing cell suspensions. Dysgalacticin blocked transport of both glucose and 2DG, indicating that dysgalacticin targets the phosphoenolpyruvate-dependent glucose- and mannose-phosphotransferase system (PTS) of S. pyogenes. This inhibitory activity was voltage-independent, and in addition to the inhibition of glucose transport, dysgalacticin increased the permeability of the cytoplasmic membrane mediating leakage of intracellular potassium ions. Moreover, dysgalacticin dissipated the membrane potential and inhibited [ 14 C]serine uptake, a membrane potential-dependent process in S. pyogenes. Conclusions: Taken together, these data indicate that dysgalacticin targets the glucose- and/or mannose-PTS as a receptor leading to inhibition of sugar uptake. As a result of this interaction, dysgalacticin perturbs membrane integrity leading to loss of intracellular K + ions and dissipation of the membrane potential, ultimately leading to cell death. |
Databáze: | OpenAIRE |
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