Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia

Abstract

Stenotrophomonas maltophilia, an environmental Gram-negative bacterium, is an emerging nosocomial opportunistic pathogen that causes life-threatening infections in immunocompromised patients and chronic pulmonary infections in cystic fibrosis patients. Due to increasing resistance to multiple classes of antibiotics, S. maltophilia infections are difficult to treat successfully. This makes the search for new antimicrobial strategies mandatory. In this study, the antibacterial activity of the heterocyclic corticosteroid deflazacort and several of its synthetic precursors was tested against S. maltophilia. All compounds were not active against standard strain S. maltophilia K279a. The compound PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) showed a weak effect against some S. maltophilia clinical isolates, but exhibited a synergistic effect with aminoglycosides. PYED-1 at sub-inhibitory concentrations decreased S. maltophilia biofilm formation. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis demonstrated that the expression of biofilm- and virulence- associated genes (StmPr1, StmPr3, sphB, smeZ, bfmA, fsnR) was significantly suppressed after PYED-1 treatment. Interestingly, PYED-1 also repressed the expression of the genes aph (3′)-IIc, aac (6′)-Iz, and smeZ, involved in the resistance to aminoglycosides.

Steroid Derivatives as Potential Antimicrobial Agents against Staphylococcus aureus Planktonic Cells

“…The time-kill curve analysis against S. aureus demonstrated a concentration-dependent rapid bactericidal activity of PYED-1 (Figure 4). In line with this, we have previously shown that PYED-1 exhibited bactericidal activity against S. maltophilia, and that the permeabilization of the bacterial membrane might contribute to the effect [7]. Our study demonstrated additivity of PYED-1/gentamicin and PYED-1/oxacillin combinations by checkerboard assay.…”

“…PYED-1 exerted a good inhibitory activity against E. faecalis, S. aureus, and A. baumannii, low to moderate activity against E. coli and P. aeruginosa, while it did not exert any appreciable inhibition against K. pneumoniae and E. aerogenes ( Tables 2 and 3). A weak effect was also observed in a previous report against S. maltophilia [7].…”

“…In the frame of a study devoted to the development of a novel and convenient synthetic strategy for the preparation of DFZ, we recently found that a DFZ synthetic precursor called PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1), exhibited a good antibacterial activity against Staphylococcus aureus ATCC 29213 and Acinetobacter baumannii ATCC 17978 without showing cytotoxicity [6]. In addition, we demonstrated that PYED-1 has a weak effect against Stenotrophomonas maltophilia clinical isolates but at sub-inhibitory concentrations it inhibits biofilm formation of the reference S. maltophilia K279a strain [7].…”

PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of Staphylococcus aureus

“…Furthermore, PYED-1 at concentrations of up to 8 µg/mL did not impair planktonic growth at concentrations of up to 8 µg/mL (data not shown), thus suggesting that the reduction of biofilm formation caused by PYED-1 was due to its antibiofilm activity, and not to its antimicrobial activity. Similar results were obtained in previous studies on S. maltophilia [12], in which treatment with PYED-1 at 1/4× MIC, 1/8× MIC, and 1/16× MIC was able to inhibit biofilm formation by 97%, 90%, and 57%, respectively, compared with the untreated control. Biofilm formation was also assessed qualitatively using confocal laser scanning microscopy (CLSM).…”

“…In previous studies, we showed that pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1 (PYED-1) exhibits effective antibacterial activity against S. aureus ATCC 29213 and A. baumannii ATCC 17978, without cytotoxic effects [10,11]. Additionally, we demonstrated that PYED-1 at sub-inhibitory concentrations hinders the biofilm formation of the Stenotrophomonas maltophilia K279a strain [12].…”