Antimicrobial Activity of Lipopeptides

Czechowicz, Paulina; Nowicka, J

doi:10.21307/pm-2018.57.3.213

Cited by 4 publications

(15 citation statements)

References 71 publications

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“…causing VVC clinically refractory to first-line therapy often show sensitivity to fluconazole under laboratory conditions [ 57 , 58 ]. It has been suggested that the key factor of the virulence responsible for the lack of therapeutic effects may be the ability to create biofilms [ 46 , 51 , 59 ]. For this reason, it is necessary to search for alternative methods of treating fungal infections based on antimicotics that effectively eradicate this structure.…”

Section: Discussionmentioning

confidence: 99%

The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections

et al. 2021

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Fungi from the Candida genus are widespread commensals and, at the same time, are the leading cause of fungal infections worldwide. For instance, vulvovaginal candidiasis (VVC) affects approximately 75% of women at least once in their lifetime, remaining the second most common gynecological infection. On the contrary, hospital-acquired fungal bloodstream infections (BSIs), although less frequent, are characterized by a high mortality rate. Undoubtedly, the main reason for this situation are virulence factors that these yeast-like fungi can produce, and the ability to form a biofilm is one of the most important of them. Due to the low effectiveness of classic antimycotics against Candida biofilms, an intense search for new drugs capable of eradicating this structure is highly demanded. One of the most promising groups of compounds exhibiting such properties are antimicrobial peptides (AMPs). This study focuses on a comparison of the efficacy of Omiganan and fluconazole alone and in combination against Candida strains isolated from BSIs. The obtained results are consistent with our previous reports on the effectiveness of Omiganan against clinical strains isolated from VVC. This is also the first report on the combinatory application of Omiganan in the context of fungal BSI. The majority of combinations with fluconazole showed an additive effect, as well as a synergistic effect in the range of certain concentrations. Importantly, such effects are visible at concentrations much lower than for those compounds used individually. Potentially, this entails the possibility of limiting the adverse effects (e.g., toxicity) of Omiganan and fluconazole applied in vivo, thus improving the safety profile of this particular antifungal therapy.

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Section: Discussionmentioning

confidence: 99%

The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections

et al. 2021

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“…AMPs (including lipopeptides) are among antimicrobial compounds that are of great interest for researchers, especially in recent years. These are compounds with a broad spectrum of activity and a different mechanism of action compared to traditional antibiotics, which makes it much more di cult for microorganisms to acquire resistance to them [13][14][15]18 . The compounds used in this study were ultrashort cationic lipopeptides (USCLs).…”

Section: Discussionmentioning

confidence: 99%

“…Usually, USCLs are rich in arginine or lysine, which makes them cationic (net positive charge). Owing to this structure, USCLs interact with the membrane bilayers of various microorganisms, permeabilize them and cause cell death [13][14][15]18 . Based on our previous study, compounds with the most potent antifungal and antibio lm activities were selected.…”

Section: Discussionmentioning

confidence: 99%

“…One of the promising classes of compounds are lipopeptides [12][13][14][15] . In general, lipopeptides consist of a peptide fragment and conjugated lipid residue(s).…”

Section: Introductionmentioning

confidence: 99%

“…In the case of fungi, lipopeptides interact with negatively charged residues of sialic acid and phosphatidylinositol found in the cell membrane of these microorganisms 16,17 . Their mode of action is based on the permeabilization of the membrane bilayers, what leads to cell death [13][14][15]18 . They can exhibit plenty of biological properties, such as antibacterial, antifungal, antibio lm, antiadhesive, anticancer and surface activities 19 .…”

Section: Introductionmentioning

confidence: 99%

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Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole Against Vulvovaginal Candida spp.

Czechowicz

Neubauer

Nowicka

et al. 2021

Preprint

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Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results showed that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity than their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed the synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis.

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Activity of Novel Ultrashort Cyclic Lipopeptides against Biofilm of Candida albicans Isolated from VVC in the Ex Vivo Animal Vaginal Model and BioFlux Biofilm Model—A Pilot Study

Czechowicz

Nowicka

Neubauer

et al. 2022

IJMS

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In recent years, clinicians and doctors have become increasingly interested in fungal infections, including those affecting the mucous membranes. Vulvovaginal candidiasis (VVC) is no exception. The etiology of this infection remains unexplained to this day, as well as the role and significance of asymptomatic vaginal Candida colonization. There are also indications that in the case of VVC, standard methods of determining drug susceptibility to antifungal drugs may not have a real impact on their clinical effectiveness—which would explain, among other things, treatment failures and relapse rates. The aim of the study was to verify the promising results obtained previously in vitro using standard methods, in a newly developed ex vivo model, using tissue fragments of the mouse vagina. The main goal of the study was to determine whether the selected ultrashort cyclic lipopeptides (USCLs) and their combinations with fluconazole at specific concentrations are equally effective against Candida forming a biofilm directly on the surface of the vaginal epithelium. In addition, the verification was also performed with the use of another model for the study of microorganisms (biofilms) in vitro—the BioFlux system, under microfluidic conditions. The obtained results indicate the ineffectiveness of the tested substances ex vivo at concentrations eradicating biofilm in vitro. Nevertheless, the relatively most favorable and promising results were still obtained in the case of combination therapy—a combination of low concentrations of lipopeptides (mainly linear analogs) with mycostatic fluconazole. Additionally, using BioFlux, it was not possible to confirm the previously obtained results. However, an inhibiting effect of the tested lipopeptides on the development of biofilm under microfluidic conditions was demonstrated. There is an incompatibility between the classic in vitro methods, the newer BioFlux method of biofilm testing, offering many advantages postulated elsewhere, and the ex vivo method. This incompatibility is another argument for the need, on the one hand, to intensify research on the pathomechanism of VVC, and, on the other hand, to verify and maybe modify the standard methods used in the determination of Candida susceptibility.

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Antimicrobial Activity of Lipopeptides

Cited by 4 publications

References 71 publications

The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections

The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections

Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole Against Vulvovaginal Candida spp.

Activity of Novel Ultrashort Cyclic Lipopeptides against Biofilm of Candida albicans Isolated from VVC in the Ex Vivo Animal Vaginal Model and BioFlux Biofilm Model—A Pilot Study

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