Abstract
N-acyl homoserine lactones (AHLs) are quorum sensing (QS) signal molecules used by most Gram-negative pathogenic bacteria. In this article the lactonase activity of the preparations based on hexahistidine-tagged organophosphorus hydrolase (His6-OPH) towards AHLs was studied. Initially, three of the most interesting β-lactam antibiotics were selected from seven that were trialed during molecular docking to His6-OPH. Combinations of antibiotics (meropenem, imipenem, ceftriaxone) and His6-OPH taken in the native form or in the form of non-covalent enzyme-polyelectrolyte complexes (EPCs) with poly(glutamic acid) or poly(aspartic acid) were obtained and investigated. The lactonase activity of the preparations was investigated under different physical-chemical conditions in the hydrolysis of AHLs [N-butyryl-D,L-homoserine lactone, N-(3-oxooctanoyl)-D,L-homoserine lactone, N-(3-oxododecanoyl)-L-homoserine lactone]. An increased efficiency of catalytic action and stability of the lactonase activity of His6-OPH was shown for its complexes with antibiotics and was confirmed in trials with bacterial strains. The broadening of the catalytic action of the enzyme against AHLs was revealed in the presence of the meropenem. Results of molecular docking of AHLs to the surface of the His6-OPH dimer in the presence of antibiotics allowed proposing the mechanism of such interference based on a steric repulsion of the carbon chain of hydrolyzed AHLs by the antibiotics bounded to the enzyme surface.
Funding source: Russian Science Foundation
Award Identifier / Grant number: 16-14-00061
Funding statement: This work was supported by the Russian Science Foundation (Funder Id: 10.13039/501100006769, Grant No. 16-14-00061).
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Supplementary Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0162).
©2018 Walter de Gruyter GmbH, Berlin/Boston
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Articles in the same Issue
- Frontmatter
- Reviews
- Exploratory cell dynamics: a sense of touch for cells?
- Kallikrein-related peptidases and associated microRNAs as promising prognostic biomarkers in gastrointestinal malignancies
- Sphingolipid metabolism – an ambiguous regulator of autophagy in the brain
- Minireview
- Insulin-like signaling within and beyond metazoans
- Research Articles/Short Communications
- Genes and Nucleic Acids
- Oxidation of 1-N2-etheno-2′-deoxyguanosine by singlet molecular oxygen results in 2′-deoxyguanosine: a pathway to remove exocyclic DNA damage?
- Protein Structure and Function
- Novel approach to quorum quenching: rational design of antibacterials in combination with hexahistidine-tagged organophosphorus hydrolase
- The forkhead domain hinge-loop plays a pivotal role in DNA binding and transcriptional activity of FOXP2
- New clues into the self-assembly of Vmh2, a basidiomycota class I hydrophobin
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- Model construction of Niemann-Pick type C disease in zebrafish
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