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- Gerner, Erik, 1986, et al.
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Sodium Salicylate Influences the Pseudomonas aeruginosa Biofilm Structure and Susceptibility Towards Silver
- 2021
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:3
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Journal article (peer-reviewed)abstract
- Hard-to-heal wounds are typically infected with biofilm-producing microorganisms, such as Pseudomonas aeruginosa, which strongly contribute to delayed healing. Due to the global challenge of antimicrobial resistance, alternative treatment strategies are needed. Here, we investigated whether inhibition of quorum sensing (QS) by sodium salicylate in different P. aeruginosa strains (QS-competent, QS-mutant, and chronic wound strains) influences biofilm formation and tolerance to silver. Biofilm formation was evaluated in simulated serum-containing wound fluid in the presence or absence of sodium salicylate (NaSa). Biofilms were established using a 3D collagen-based biofilm model, collagen coated glass, and the Calgary biofilm device. Furthermore, the susceptibility of 48-h-old biofilms formed by laboratory and clinical strains in the presence or absence of NaSa towards silver was evaluated by assessing cell viability. Biofilms formed in the presence of NaSa were more susceptible to silver and contained reduced levels of virulence factors associated with biofilm development than those formed in the absence of NaSa. Biofilm aggregates formed by the wild-type but not the QS mutant strain, were smaller and less heterogenous in size when grown in cultures with NaSa compared to control. These data suggest that NaSa, via a reduction of cell aggregation in biofilms, allows the antiseptic to become more readily available to cells.
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- Gerner, Erik, 1986, et al.
(author)
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Sodium salicylate interferes with quorum-sensing-regulatedvirulence in chronic wound isolates of Pseudomonas aeruginosa in simulated wound fluid
- 2020
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In: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 69:5, s. 767-780
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Journal article (peer-reviewed)abstract
- Introduction. An important factor for delayed healing of chronic wounds is the presence of bacteria. Quorum sensing (QS), a cell density-dependent signalling system, controls the production of many virulence factors and biofilm formation in Pseudomonas aeruginosa.Aim. Inhibition by sodium salicylate (NaSa) of QS-regulated virulence expression was evaluated in QS-characterized clinical wound isolates of P. aeruginosa, cultured in serum-containing medium.Methodology. Fourteen clinical P. aeruginosa strains from chronic wounds were evaluated for the production of QS signals and virulence factors. Inhibition of QS by NaSa in P. aeruginosa clinical strains, wild-type PAO1 and QS reporter strains was evaluated using in vitro assays for the production of biofilm, pyocyanin, siderophores, alkaline protease, elastase and stapholytic protease.Results. Six clinical strains secreted several QS-associated virulence factors and signal molecules and two were negative for all factors. Sub-inhibitory concentrations of NaSa downregulated the expression of the QS-related genes lasB, rhlA and pqsA and reduced the secretion of several virulence factors in PAO1 and clinical strains cultured in serum. Compared to serum-free media, the presence of serum increased the expression of QS genes and production of siderophores and pyocyanin but decreased biofilm formation.Conclusions.Pseudomonas aeruginosa from chronic wound infections showed different virulence properties. While very few strains showed no QS activity, approximately half were highly virulent and produced QS signals, suggesting that the targeting of QS is a viable and relevant strategy for infection control. NaSa showed activity as a QS-inhibitor by lowering the virulence phenotypes and QS signals at both transcriptional and extracellular levels.
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- Gerner, Erik, 1986, et al.
(author)
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Targeting Pseudomonas aeruginosa quorum sensing with sodium salicylate modulates immune responses in vitro and in vivo.
- 2023
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In: Frontiers in cellular and infection microbiology. - 2235-2988. ; 13
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Journal article (peer-reviewed)abstract
- Chronic infections are a major clinical challenge in hard-to-heal wounds and implanted devices. Pseudomonas aeruginosa is a common causative pathogen that produces numerous virulence factors. Due to the increasing problem of antibiotic resistance, new alternative treatment strategies are needed. Quorum sensing (QS) is a bacterial communication system that regulates virulence and dampens inflammation, promoting bacterial survival. QS inhibition is a potent strategy to reduce bacterial virulence and alleviate the negative impact on host immune response.This study investigates how secreted factors from P. aeruginosa PAO1, cultured in the presence or absence of the QS inhibitor sodium salicylate (NaSa), influence host immune response.In vitro, THP-1 macrophages and neutrophil-like HL-60 cells were used. In vivo, discs of titanium were implanted in a subcutaneous rat model with local administration of P. aeruginosa culture supernatants. The host immune response to virulence factors contained in culture supernatants (+/-NaSa) was characterized through cell viability, migration, phagocytosis, gene expression, cytokine secretion, and histology.In vitro, P. aeruginosa supernatants from NaSa-containing cultures significantly increased THP-1 phagocytosis and HL-60 cell migration compared with untreated supernatants (-NaSa). Stimulation with NaSa-treated supernatants in vivo resulted in: (i) significantly increased immune cell infiltration and cell attachment to titanium discs; (ii) increased gene expression of IL-8, IL-10, ARG1, and iNOS, and (iii) increased GRO-α protein secretion and decreased IL-1β, IL-6, and IL-1α secretion, as compared with untreated supernatants.In conclusion, treating P. aeruginosa with NaSa reduces the production of virulence factors and modulates major immune events, such as promoting phagocytosis and cell migration, and decreasing the secretion of several pro-inflammatory cytokines.
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- Gerner, Erik, 1986
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The role of sodium salicylate as a virulence inhibitor for soft tissue infections
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Approximately 2% of the total population will suffer from chronic wounds during their lifetime. These wounds can last for years and are associated with considerable patient suffering and large socioeconomic costs. Infection is considered an important factor for delayed healing. Due to the continued development of antibiotic resistance, novel alternative treatment strategies are urgently needed. Quorum sensing (QS), a signalling system used by important wound pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, regulates the production of virulence factors and is thus an attractive target. The aim of this thesis was to evaluate the effect of sodium salicylate (NaSa) on P. aeruginosa and S. aureus QS activity and the production of virulence factors and how this influences the host immune response both in vitro and in vivo. Furthermore, a collection of P. aeruginosa chronic wound isolates was characterized in terms of QS signalling and virulence factor production. The results showed that approximately 50% of the clinical P. aeruginosa strains produced the majority of the investigated virulence factors and QS signals. In P. aeruginosa, NaSa reduced QS activity and the production of virulence factors, such as pyocyanin, pyoverdine, proteases and biofilm. In the presence of NaSa, P. aeruginosa formed smaller biofilm aggregates, which were more easily eradicated by silver. In S. aureus, the effect of NaSa on QS and virulence factor production was concentration dependent. Specifically, high levels of NaSa reduced QS and virulence production, whereas the opposite was observed for lower NaSa concentrations. In some instances, biofilm formation was induced by NaSa but without increasing its tolerance towards silver or antibiotics. In vitro, immune cells stimulated with supernatants from NaSa-treated P. aeruginosa cultures demonstrated increased migration and phagocytic capacity compared to untreated supernatants. In vivo, rats stimulated with NaSa-treated supernatants showed increased immune cell infiltration and reduced secretion of proinflammatory cytokines. In conclusion, NaSa influences QS and virulence factor production in P. aeruginosa and S. aureus, resulting in the stimulation of important immune functions in vitro and in vivo.
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