Search Results (7)

Diabetic foot infections (DFIs) are frequently linked to diabetic-related morbidity and death because of the ineffectiveness of conventional antibiotics against multidrug-resistant bacteria. Pexiganan and nisin A are antimicrobial peptides (AMPs), and their application may complement conventional antibiotics in DFI treatment. A collagen 3D model, previously established to mimic a soft-tissue collagen matrix, was used to evaluate the antibacterial efficacy of a guar gum gel containing pexiganan and nisin alone and combined with three antimicrobials toward the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa isolated from infected foot ulcers. Antimicrobials and bacterial diffusion were confirmed by spot-on-lawn and bacterial growth by bacterial count (cfu/mL). Our main conclusion was that the dual-AMP biogel combined with gentamicin, clindamycin, or vancomycin was not able to significantly reduce bacterial growth or eradicate S. aureus and P. aeruginosa DFI isolates. We further reported an antagonism between dual-AMP and dual-AMP combined with antibiotics against S. aureus. Full article

Periodontal disease is a relevant oral disease in dogs and nisin–biogel has been previously proposed to be used in its control. Enterococci, as inhabitants of the oral cavity with a high genetic versatility, are a reliable bacterial model for antimicrobial studies. Our goal was to evaluate the in vivo influence of the long-term dental application of the nisin–biogel on the virulence and antimicrobial signatures of canine oral enterococci. Twenty dogs were randomly allocated to one of two groups (treatment group—TG with nisin–biogel dental application, or control group—CG without treatment) and submitted to dental plaque sampling at day 0 and after 90 days (T90). Samples were processed for Enterococcus spp. isolation, quantification, identification, molecular typing and antimicrobial and virulence characterization. From a total of 140 enterococci, molecular typing allowed us to obtain 70 representative isolates, mostly identified as E. faecalis and E. faecium. No significant differences (p > 0.05) were observed in the virulence index of the isolates obtained from samples collected from the TG and CG at T90. At T90, a statistically significant difference (p = 0.0008) was observed in the antimicrobial resistance index between the isolates from the TC and CG. Oral enterococci were revealed to be reservoirs of high resistant and virulent phenotypes. Full article

Periodontal disease (PD) is a common oral disease in dogs. Recent in vitro research revealed that nisin–biogel is a promising compound for canine PD control. In this work, a clinical trial was developed to assess the in vivo efficacy of nisin–biogel in dogs by determining the dental plaque index (DPI), gingivitis index (GI), and periodontal pocket depth (PPD) after dental administration. The biogel’s influence on aerobic bacteria counts was also evaluated, as well as its acceptance/adverse effects in dogs. Twenty animals were allocated to one of two groups: a treatment group (TG) subjected to a dental topical application of nisin–biogel for 90 days and a control group (CG) with no treatment. Besides daily monitoring, on day 1 (T0) and at the end of the assay (T90), animals were subjected to blood analysis, periodontal evaluation, dental plaque sampling, scaling, and polishing. Statistical analysis with mixed models showed a significant reduction in mean PPD (estimate = −0.371, p-value < 0.001) and DPI (estimate = −0.146, p-value < 0.05) in the TG animals at T90. A reduction in the GI (estimate = −0.056, p-value > 0.05) was also observed but with no statistical significance. No influence on total bacterial counts was observed, and no adverse effects were detected. The nisin–biogel was revealed to be a promising compound for canine PD control. Full article

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. Full article

Staphylococcus aureus is the most prevalent pathogen in diabetic foot infections (DFIs). In addition to its ability to express several virulence factors, including the formation of recalcitrant biofilms, S. aureus is also becoming increasingly resistant to most antibiotics used in clinical practice. The search for alternative treatment strategies for DFI is urgently needed. Antimicrobial peptides (AMPs), namely, nisin, are emerging as potential new therapeutics for managing DFIs. Our team has developed a nisin-guar gum biogel to be applied to DFIs. In this study, to confirm its future in vivo applicability, we evaluated the influence of four storage temperatures (−20 °C, 4 °C, 22 °C, and 37 °C) during a 24 months storage period on its antimicrobial activity towards DFI S. aureus, and its cytotoxicity, to a human keratinocyte cell line. When stored at temperatures below 22 °C, the biogel antimicrobial activity was not significantly influenced by storage duration or temperature. Moreover, nisin incorporated within the guar gum biogel exhibited no significant levels of cytotoxicity on human keratinocyte cells, confirming its potential for DFIs therapeutics. In conclusion, results confirm that the nisin-biogel is a potential candidate to be used as an alternative or complement compound for conventional DFI therapeutics. Full article

Background: Periodontal disease (PD) is a highly prevalent inflammatory disease in dogs. This disease is initiated by a polymicrobial biofilm on the teeth surface, whose control includes its prevention and removal. Recently, it was shown that nisin displays antimicrobial activity against canine PD-related bacteria. Moreover, guar gum biogel has shown to be a promising topical delivery system for nisin. Methods: In this study we aimed to evaluate the antimicrobial activity of the nisin-biogel in the presence of canine saliva and after a 24-month storage, at different conditions, using a canine oral enterococci collection. We also studied the nisin-biogel cytotoxicity using a Vero cell line and canine primary intestinal fibroblasts. Results: The presence of saliva hampers nisin-biogel antimicrobial activity, and higher nisin concentrations were required for an effective activity. A significant reduction (p ≤ 0.05) in inhibitory activity was observed for nisin-biogel solutions stored at 37 °C, over a 24-month period, which was not observed with the other conditions. The nisin-biogel showed no cytotoxicity against the cells tested at concentrations up to 200 µg/mL. Conclusions: Our results confirmed the potential of the nisin-biogel for canine PD control, supporting the development of an in vivo clinical trial. Full article

Diabetic foot ulcers (DFUs) are major complications of Diabetes mellitus being responsible for significant morbidity and mortality. DFUs frequently become chronically infected by a complex community of bacteria, including multidrug-resistant and biofilm-producing strains of Staphylococcus aureus and Pseudomonas aeruginosa. Diabetic foot infections (DFI) are often recalcitrant to conventional antibiotics and alternative treatment strategies are urgently needed. Antimicrobial Peptides (AMPs), such as pexiganan and nisin, have been increasingly investigated and reported as effective antimicrobial agents. Here, we evaluated the antibacterial potential of pexiganan and nisin used in combination (dual-AMP) to control the growth of planktonic and biofilm co-cultures of S. aureus and P. aeruginosa clinical strains, co-isolated from a DFU. A DFU collagen three-dimensional (3D) model was used to evaluate the distribution and efficacy of AMPs locally delivered into the model. The concentration of pexiganan required to inhibit and eradicate both planktonic and biofilm-based bacterial cells was substantially reduced when used in combination with nisin. Moreover, incorporation of both AMPs in a guar gum delivery system (dual-AMP biogel) did not affect the dual-AMP antimicrobial activity. Importantly, the application of the dual-AMP biogel resulted in the eradication of the S. aureus strain from the model. In conclusion, data suggest that the local application of the dual-AMPs biogel constitutes a potential complementary therapy for the treatment of infected DFU. Full article