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Open AccessArticle

Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5H)-Furanone Derivative against Staphylococcus aureus

1
Laboratory of Molecular Genetics of Microorganisms, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya street, Kazan 420008, Republic of Tatarstan, Russia
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Laboratory of Bionanotechnology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kreml uramı 18, Kazan 420008, Republic of Tatarstan, Russia
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Biofunctional Chemistry Laboratory, Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya street, Kazan 420008, Republic of Tatarstan, Russia
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Interdisciplinary Centre for Proteomic Research, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya street, Kazan 420008, Republic of Tatarstan, Russia
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Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, Kazan 420088, Republic of Tatarstan, Russia
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Biomedical Engineering Research Centre, St. Petersburg Electrotechnical University, St. Petersburg 197022, Russia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 694; https://doi.org/10.3390/ijms20030694
Received: 11 December 2018 / Revised: 29 January 2019 / Accepted: 3 February 2019 / Published: 6 February 2019
(This article belongs to the Section Molecular Microbiology)
Staphylococcus aureus causes various infectious diseases, from skin impetigo to life-threatening bacteremia and sepsis, thus appearing an important target for antimicrobial therapeutics. In turn, the rapid development of antibiotic resistance and biofilm formation makes it extremely robust against treatment. Here, we unravel the molecular mechanism of the antimicrobial activity of the recently unveiled F105 consisting of three pharmacophores: chlorinated 2(5H)-furanone, sulfone, and l-menthol moieties. F105 demonstrates highly selective activity against Gram-positive bacteria and biofilm-embedded S. aureus and exhibits low risk of resistance development. We show explicitly that the fluorescent analogue of F105 rapidly penetrates into Gram-positive bacteria independently of their cell integrity and viability and accumulates there. By contrast, Gram-negative bacteria remain impermeable and, therefore, insusceptible to F105. Apparently, in bacterial cells, F105 induces reactive oxygen species (ROS) formation and nonspecifically interacts with a number of proteins, including ROS-utilizing ones. Using native and 2D PAGE, we confirm that F105 changes the charge of some proteins by either oxidation or direct interaction with them. Therefore, it seems justified to conclude that being simultaneously a ROS inducer and damaging proteins responsible for ROS utilization, F105 impairs the cellular anti-ROS defense representing a prospective ROS-inducing antibacterial agent. View Full-Text
Keywords: 2(5H)-furanones; biofilms; drug discovery; ROS; Staphylococci 2(5H)-furanones; biofilms; drug discovery; ROS; Staphylococci
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MDPI and ACS Style

Sharafutdinov, I.S.; Pavlova, A.S.; Akhatova, F.S.; Khabibrakhmanova, A.M.; Rozhina, E.V.; Romanova, Y.J.; Fakhrullin, R.; Lodochnikova, O.A.; Kurbangalieva, A.R.; Bogachev, M.I.; Kayumov, A.R. Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5H)-Furanone Derivative against Staphylococcus aureus. Int. J. Mol. Sci. 2019, 20, 694. https://doi.org/10.3390/ijms20030694

AMA Style

Sharafutdinov IS, Pavlova AS, Akhatova FS, Khabibrakhmanova AM, Rozhina EV, Romanova YJ, Fakhrullin R, Lodochnikova OA, Kurbangalieva AR, Bogachev MI, Kayumov AR. Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5H)-Furanone Derivative against Staphylococcus aureus. International Journal of Molecular Sciences. 2019; 20(3):694. https://doi.org/10.3390/ijms20030694

Chicago/Turabian Style

Sharafutdinov, Irshad S.; Pavlova, Anna S.; Akhatova, Farida S.; Khabibrakhmanova, Alsu M.; Rozhina, Elvira V.; Romanova, Yulia J.; Fakhrullin, Rawil; Lodochnikova, Olga A.; Kurbangalieva, Almira R.; Bogachev, Mikhail I.; Kayumov, Airat R. 2019. "Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5H)-Furanone Derivative against Staphylococcus aureus" Int. J. Mol. Sci. 20, no. 3: 694. https://doi.org/10.3390/ijms20030694

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