Silicone Foley catheters impregnated with microbial indole derivatives inhibit crystalline biofilm formation by Proteus mirabilis
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Date
2022-09-02
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Frontiers Media S.A.
Series Info
frontiers Frontiers in Cellular and Infection Microbiology;
Scientific Journal Rankings
Abstract
Proteus mirabilis is a common causative agent for catheter-associated urinary
tract infections (CAUTI). The crystalline biofilm formation by P. mirabilis causes
catheter encrustation and blockage leading to antibiotic treatment resistance.
Thus, biofilm formation inhibition on catheters becomes a promising
alternative for conventional antimicrobial-based treatment that is associated
with rapid resistance development. Our previous work has demonstrated the in
vitro antibiofilm activity of microbial indole derivatives against clinical isolates of
P. mirabilis. Accordingly, we aim to evaluate the capacity of silicone Foley
catheters (SFC) impregnated with these indole derivatives to resist biofilm
formation by P. mirabilis both phenotypically and on the gene expression
level. Silicon Foley catheter was impregnated with indole extract recovered
from the supernatant of the rhizobacterium Enterobacter sp. Zch127 and the
antibiofilm activity was determined against P. mirabilis (ATCC 12435) and
clinical isolate P8 cultured in artificial urine. The indole extract at sub-
minimum inhibitory concentration (sub-MIC=0.5X MIC) caused a reduction
in biofilm formation as exhibited by a 60-70% reduction in biomass and three
log10 in adhered bacteria. Results were confirmed by visualization by scanning
electron microscope. Moreover, changes in the relative gene expression of the
virulence genes confirmed the antibiofilm activity of the indole extract against
P. mirabilis. Differential gene expression analysis showed that extract Zch127 at
its sub-MIC concentration significantly down-regulated genes associated with
swarming activity: umoC, flhC, flhD, flhDC, and mrpA (p< 0.001). In addition,
Zch127 extract significantly down-regulated genes associated with polyamine
synthesis: speB and glnA (p< 0.001), as well as the luxS gene associated with
quorum sensing. Regulatory genes for capsular polysaccharide formation; rcsB
and rcsD were not significantly affected by the presence of the indole
derivatives. Furthermore, the impregnated catheters and the indole extract
showed minimal or no cytotoxic effect against human fibroblast cell lines
indicating the safety of this intervention. Thus, the indole-impregnated catheter is proposed to act as a suitable and safe strategy for reducing
P. mirabilis CAUTIs.
Description
Keywords
Proteus mirabilis, urinary catheters, indole derivatives, crystalline biofilm, antibiofilm, gene expression