Binding of azole antibiotics to Staphylococcus aureus flavohemoglobin increases intracellular oxidative stress.

Journal of Bacteriology
Lígia S NobreLígia M Saraiva

Abstract

In this work, we report that flavohemoglobin contributes to the azole susceptibility of Staphylococcus aureus. We first observed that deletion of the flavohemoglobin gene leads to an increase in the viability of imidazole-treated S. aureus cells and that reversion to the wild-type phenotype occurs upon expression of flavohemoglobin from a multicopy plasmid. Further spectroscopic analyses showed that miconazole, the most efficient azole antibiotic against S. aureus, ligates to heme of both oxidized and reduced flavohemoglobin. The binding of miconazole to oxidized flavohemoglobin, with an association constant of 1.7 x 10(6) M(-1), typical of a tight, specific binding equilibrium, results in augmentation of the superoxide production by the enzyme. These results are corroborated by in vivo studies showing that imidazole-treated S. aureus cells expressing flavohemoglobin contain a larger amount of reactive oxygen species. Moreover, it was observed that the survival of miconazole-treated S. aureus internalized by murine macrophages is higher for cells lacking flavohemoglobin. Altogether, the present data revealed that in S. aureus, flavohemoglobin enhances the antimicrobial activity of imidazoles via an increase of intracellular oxi...Continue Reading

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Citations

May 9, 2012·Journal of Bacteriology·Joana M BaptistaLígia M Saraiva
Sep 20, 2012·The Journal of General and Applied Microbiology·Koh FukushimaSatoru Suzuki
May 3, 2014·Applied Biochemistry and Biotechnology·Aymen EzzineLaura Baciou
Jan 1, 2012·Scientifica·Paul R Gardner
Feb 22, 2012·Free Radical Biology & Medicine·Michael T Forrester, Matthew W Foster
Apr 2, 2013·Biochimica Et Biophysica Acta·Serge N VinogradovDavid Hoogewijs
Apr 9, 2009·Biochemical and Biophysical Research Communications·Shengmin ZhouHirofumi Shoun
Feb 1, 2017·Biomaterials Science·T CavoueD-L Versace
Jan 1, 2019·Microscopy Research and Technique·Rafaela Fernandes ZancanMarco Antonio Hungaro Duarte
Mar 5, 2017·Essays in Biochemistry·Katharina RichterTom Coenye
Dec 12, 2020·Breastfeeding Medicine : the Official Journal of the Academy of Breastfeeding Medicine·Ryan Colton BettsKatrina B Mitchell
Oct 20, 2021·FEMS Microbiology Letters·Sandra M CarvalhoLígia M Saraiva

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