Efflux Pumps of Burkholderia thailandensis Control the Permeability Barrier of the Outer Membrane
| Autor: | Ganesh Krishnamoorthy, Zhen Zhang, Jon W. Weeks, Robert K. Ernst, Helen I. Zgurskaya, Herbert P. Schweizer, Courtney E. Chandler, Haotian Xue |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Burkholderia pseudomallei
medicine.drug_class Burkholderia Polymyxin Antibiotics Microbial Sensitivity Tests Microbiology Lipid A 03 medical and health sciences Antibiotic resistance Bacterial Proteins Mechanisms of Resistance Drug Resistance Multiple Bacterial medicine Pharmacology (medical) Phylogeny 030304 developmental biology Pharmacology 0303 health sciences Burkholderia thailandensis biology 030306 microbiology Chemistry Membrane Transport Proteins biology.organism_classification Anti-Bacterial Agents Infectious Diseases Efflux Bacterial outer membrane Bacterial Outer Membrane Proteins |
| Popis: | Burkholderia comprises species that are significant biothreat agents and common contaminants of pharmaceutical production facilities. Their extreme antibiotic resistance affects all classes of antibiotics, including polycationic polymyxins and aminoglycosides. The major underlying mechanism is the presence of two permeability barriers, the outer membrane with modified lipid A moieties and active drug efflux pumps. The two barriers are thought to be mechanistically independent and act synergistically to reduce the intracellular concentrations of antibiotics. In this study, we analyzed the interplay between active efflux pumps and the permeability barrier of the outer membrane in Burkholderia thailandensis. We found that three efflux pumps, AmrAB-OprA, BpeEF-OprC, and BpeAB-OprB, of B. thailandensis are expressed under standard laboratory conditions and provide protection against multiple antibiotics, including polycationic polymyxins. Our results further suggest that the inactivation of AmrAB-OprA or BpeAB-OprB potentiates the antibacterial activities of antibiotics not only by reducing their efflux, but also by increasing their uptake into cells. Mass spectrometry analyses showed that in efflux-deficient B. thailandensis cells, lipid A species modified with 4-amino-4-deoxy-l-aminoarabinose are significantly less abundant than in the parent strain. Taken together, our results suggest that changes in the outer membrane permeability due to alterations in lipid A structure could be contributing factors in antibiotic hypersusceptibilities of B. thailandensis cells lacking AmrAB-OprA and BpeAB-OprB efflux pumps. |
| Databáze: | OpenAIRE |
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