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. 2020 Mar 25;8(4):468.
doi: 10.3390/microorganisms8040468.

Steroid Derivatives as Potential Antimicrobial Agents Against Staphylococcus aureus Planktonic Cells

Adriana Vollaro  1 , Anna Esposito  2 , Eleni Antonaki  1 , Vita Dora Iula  3 , Daniele D'Alonzo  2 , Annalisa Guaragna  2 , Eliana De Gregorio  1
Affiliations

Steroid Derivatives as Potential Antimicrobial Agents Against Staphylococcus aureus Planktonic Cells

Adriana Vollaro et al. Microorganisms. .

Abstract

In this work, the antibacterial activity of deflazacort and several of its synthetic precursors was tested against a panel of bacterial pathogens responsible for most drug-resistant infections including Staphylococcus aureus, Enterococcus spp., Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. The derivative of deflazacort, PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) showed the best antibacterial activity in a dose-dependent way. We focused on the action of PYED-1 against S. aureus cells. PYED-1 exhibited an additive antimicrobial effect with gentamicin and oxacillin against the methicillin-resistant S. aureus isolate 00717. In addition to its antimicrobial effect, PYED-1 was found to repress the expression of several virulence factors of S. aureus, including toxins encoded by the hla (alpha-haemolysin), hlb (beta-haemolysin), lukE-D (leucotoxins E-D), and sea (staphylococcal enterotoxin A) genes, and cell surface factors (fnbB (fibronectin-binding protein B) and capC (capsule biosynthesis protein C)). The expression levels of autolysin isaA (immunodominant staphylococcal antigen) were also increased.

Keywords: Staphylococcus aureus; anti-virulence agent; antimicrobial activity; checkerboard assay; deflazacort (DFZ); multidrug pathogens; quantitative real-time PCR; steroids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Deflazacort and its synthetic precursor PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1).
Figure 2
Figure 2
Synthetic transformations from brominated compound 9 to epoxide PYED-1.
Figure 3
Figure 3
Deflazacort (DFZ) glucocorticoid precursors and analogues.
Figure 4
Figure 4
Killing kinetics for S. aureus following treatment with the PYED-1. Growth kinetics were monitored following exposure to PYED-1 at 1 x MIC, 2 x MIC, and 4 x MIC.
See this image and copyright information in PMC

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