Abstract
A new approach to diabetic foot infections (DFIs) has been investigated, using a nisin-biogel combining the antimicrobial peptide (AMP) nisin with the natural polysaccharide guar-gum. Since in in vivo conditions bacteria may be exposed to decreased antimicrobial concentrations, known as subinhibitory concentrations (sub-MICs), effects of nisin-biogel sub-MIC values corresponding to 1/2, 1/4 and 1/8 of nisin’s minimum inhibitory concentration (MIC) on virulence expression by six Staphylococcus aureus DFI isolates was evaluated by determining bacteria growth rate; expression of genes encoding for staphylococcal protein A (spA), coagulase (coa), clumping factor A (clfA), autolysin (atl), intracellular adhesin A (icaA), intracellular adhesin D (icaD), and the accessory gene regulator I (agrI); biofilm formation; Coa production; and SpA release. Nisin-biogel sub-MICs decreased bacterial growth in a strain- and dose-dependent manner, decreased agrI, atl and clfA expression, and increased spA, coa, icaA and icaD expression. Biofilm formation increased in the presence of nisin-biogel at 1/4 and 1/8 MIC, whereas 1/2 MIC had no effect. Finally, nisin-biogel at sub-MICs did not affect coagulase production, but decreased SpA production in a dose-dependent manner. Results highlight the importance of optimizing nisin-biogel doses before proceeding to in vivo trials, to reduce the risk of virulence factor’s up-regulation due to the presence of inappropriate antimicrobial concentrations.
Highlights
Diabetes mellitus (DM) is a lifelong metabolic disorder that affects approximately 537 million people worldwide [1]
The present study evaluated the effects of nisin-biogel sub-minimum inhibitory concentration (MIC) on S. aureus Diabetic foot infections (DFIs) isolates groawnttihmriacrtoeb, viailrsuclaenncme-ordeulalatetedtgheenveisruelxepnrcesosfioSn. ,anuraemuse,lbyyoifnaflgureI,nscpinAg, cglefAne, ceoxap,raetsls, iiocanA, and icaDbi,oafiblmiliptyrotdoucfotiromn abnidoftihlme Q, SCsoyastpemro,dwuhcitcihonmaayndimSppaAct trheeleoaustec,oamime oinf sgtaapthcyoloncfoircmcailng its suiitnafbeicltiitoynfso[r31in,33v–i3v6o].aAdsmsiuncihs,trthateiopnre.sent study evaluated the effects of nisin-biogel sub
This study focused on S. aureus, S. epidermidis produces biofilm in an icaADBC-dependent manner, allowing to suggest that the time frame required for the expression of intracellular adhesin A (icaA) and intracellular adhesin D (icaD) may be identical in both species
Summary
Diabetes mellitus (DM) is a lifelong metabolic disorder that affects approximately 537 million people worldwide [1]. The effect of nisin-biogel and clindamycin at sub-MICs on virulence genes expression by S. aureus DFI isolates was investigated using RT-qPCR assays. AgrI expression levels by the S. aureus isolates tested only started to be relevant after 4 h, a period during which bacterial adherence to the host tissues already occurred in vivo At this time point, the cell-surface proteins start to be down-regulated, whereas the virulence genes associated with bacterial dissemination and biofilm formation start to be up-regulated [4,42,43]. One of the antibiotics currently applied as a DFIs alternative treatment is clindamycin, used in this study as a control to compare the effects of nisin-biogel at sub-MICs on S. aureus gene expression [21,55]. In the presence of nisin-biogel at sub-MICs levels, S. aureus DFI isolates increased SpA mRNA levels, which seems to suggest that the inhibition of virulence expression by nisin-biogel is primarily due to the blockage of protein translation at the ribosome, rather than the inhibition of virulence genes transcription
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