Efficacy of Ampicillin Against Methicillin-Resistant Staphylococcus aureus Restored Through Synergy with Branched Poly(ethylenimine)
| Autor: | Jessica M. Jensen, Robert H. Cichewicz, Stoffel Strange, Jarrod B. King, Anthony W. Friedline, Kieth J. Thomas, Susan L. Nimmo, Benjamin E. Smith, Charles V. Rice, Melissa A. Foxley, Erin M. Scull, Min T. Xiao, Daniel T. Glatzhofer |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Methicillin-Resistant Staphylococcus aureus β-lactam MRSA Microbial Sensitivity Tests Biology medicine.disease_cause Article Microbiology 03 medical and health sciences Cell Wall Vancomycin Ampicillin Drug Discovery penicillin binding protein medicine Penicillin-Binding Proteins Polyethyleneimine Pharmacology Drug Synergism biochemical phenomena metabolism and nutrition bacterial infections and mycoses Virology Methicillin-resistant Staphylococcus aureus teichoic acid Anti-Bacterial Agents Teichoic Acids 030104 developmental biology Staphylococcus aureus ampicillin medicine.drug |
| Zdroj: | The Journal of antibiotics |
| ISSN: | 0021-8820 |
| Popis: | Beta-lactam antibiotics kill Staphylococcus aureus bacteria by inhibiting the function of cell-wall penicillin binding proteins (PBPs) 1 and 3. However, β-lactams are ineffective against PBP2a, used by methicillin-resistant Staphylococcus aureus (MRSA) to perform essential cell wall crosslinking functions. PBP2a requires teichoic acid to properly locate and orient the enzyme, and thus MRSA is susceptible to antibiotics that prevent teichoic acid synthesis in the bacterial cytoplasm. As an alternative, we have used branched poly(ethylenimine), BPEI, to target teichoic acid in the bacterial cell wall. The result is restoration of MRSA susceptibility to the β-lactam antibiotic ampicillin with a MIC of 1 μg/mL, superior to that of vancomycin (MIC = 3.7 μg/mL). A checkerboard assay shows synergy of BPEI and ampicillin. Nuclear magnetic resonance (NMR) data show that BPEI alters the teichoic acid chemical environment. Laser scanning confocal microscopy (LSCM) images show BPEI residing on the bacterial cell wall where teichoic acids and PBPs are located. |
| Databáze: | OpenAIRE |
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