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.
Highlights
Stenotrophomonas maltophilia is an emerging opportunistic bacterium, which represents the third Gram-negative responsible for nosocomial infections [1,2,3]
S. maltophilia is frequently found in polymicrobial infections from the respiratory tract of cystic fibrosis (CF) patients [6]
S. maltophilia K279a was assessed by broth microdilution assay (Table 1)
Summary
Stenotrophomonas maltophilia is an emerging opportunistic bacterium, which represents the third Gram-negative responsible for nosocomial infections [1,2,3]. S. maltophilia generally causes bacteremia and pneumonia, and infections are frequently associated with complications and death in immunosuppressed or immunocompromised patients [4,5]. S. maltophilia is frequently found in polymicrobial infections from the respiratory tract of cystic fibrosis (CF) patients [6]. In CF patients, S. maltophilia infections are associated with a severe lung disease and increased risk of the need for transplantation, or death [7,8]. S. maltophilia is intrinsically resistant to carbapenems, aminoglycosides, and tetracyclines [3,16] owing to its multidrug efflux pumps and overexpression of resistant determinants, such as carbapenemases and aminoglycoside-modifying
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