AUTHOR=Sharafutdinov Irshad S. , Trizna Elena Y. , Baidamshina Diana R. , Ryzhikova Maria N. , Sibgatullina Regina R. , Khabibrakhmanova Alsu M. , Latypova Liliya Z. , Kurbangalieva Almira R. , Rozhina Elvira V. , Klinger-Strobel Mareike , Fakhrullin Rawil F. , Pletz Mathias W. , Bogachev Mikhail I. , Kayumov Airat R. , Makarewicz Oliwia 

TITLE=Antimicrobial Effects of Sulfonyl Derivative of 2(5H)-Furanone against Planktonic and Biofilm Associated Methicillin-Resistant and -Susceptible Staphylococcus aureus

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02246

DOI=10.3389/fmicb.2017.02246

ISSN=1664-302X

ABSTRACT=<p>The gram-positive opportunistic bacterium <italic>Staphylococcus aureus</italic> is one of the most common causatives of a variety of diseases including skin and skin structure infection or nosocomial catheter-associated infections. The biofilm formation that is an important virulence factor of this microorganism renders the antibiotic therapy ineffective, because biofilm-embedded bacteria exhibit strongly increased tolerance to antimicrobials. Here, we describe a novel 3-chloro-5(<italic>S</italic>)-[(1<italic>R</italic>,2<italic>S</italic>,5<italic>R</italic>)-2-isopropyl-5-methylcyclohexyloxy]-4-[4-methylphenylsulfonyl]-2(5<italic>H</italic>)-furanone (<bold>F105</bold>), possessing a sulfonyl group and <italic>l</italic>-menthol moiety. Minimal inhibitory and bactericidal concentration values (MIC and MBC) of <bold>F105</bold> were 10 and 40 mg/L, respectively, suggesting <bold>F105</bold> biocidal properties. <bold>F105</bold> exhibits pronounced activity against biofilm-embedded <italic>S. aureus</italic> and increases the efficacy of aminoglycosides (amikacin, gentamicin, and kanamycin) and benzalkonium chloride with fractional inhibitory concentration index values of 0.33–0.44 and 0.29, respectively, suggesting an alternative external treatment option, e.g., for wound infections. Moreover, low concentrations (0.5–1.3 mg/L) of <bold>F105</bold> reduced the MICs of these antimicrobials twofold. By using confocal laser scanning microscopy and CFU counting, we show explicitly that <bold>F105</bold> also restores the antimicrobial activity of gentamicin and ampicillin against <italic>S. aureus</italic> biofilms by several orders of magnitude. Biofilm structures were not destroyed but sterilized, with embedded cells being almost completely killed at twofold MBC. While <bold>F105</bold> is quite toxic (CC<sub>50</sub>/MBC ratio 0.2), our data suggest that the <bold>F105</bold> chemotype might be a promising starting point for the development of complex topical agents for combined anti-staphylococcal biofilm-therapies restoring the efficacy of some antibiotics against difficult to treat <italic>S. aureus</italic> biofilm.</p>