Vulvovaginal candidiasis (VVC) is one of the most common types of vaginal infections in women around the world and is often underestimated by both patients and doctors. Research on the pathogenesis of fungal vaginal infections over the last 20 years has resulted in a closer understanding of the virulence factors involved in Candida epithelial invasion and their mechanisms of action. Recently, attention was drawn to the enormous complexity of the interaction between yeast-like fungi and host cells, as well as the level of complexity of the host’s response to infection and their impact on the course and treatment of VVC. Our work provides a broad description of already known and some new reports on Candida virulence factors (such as phenotypic switching or biofilm formation capacity) and their importance for tissue invasion in VVC. At the same time, we also focus on interactions with host cells and local innate immune mechanisms involved in the response to vaginal fungal invasion that are now considered equally important in this case. The presented review describes the most important aspects of the still unknown pathogenicity of Candida associated with vaginal infections.
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 confirmed previous premises that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity compared to their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed a 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.
The constantly growing number of multidrug-resistant bacterial strains prompts the search for alternative treatments. Synthetic peptides based on natural antimicrobial peptides, also known as antimicrobial lipopeptides, can become a promising group of "drugs" to fight multi-resistant bacteria. The present paper discusses the origins of synthetic lipopeptides, their classification and antimicrobial properties.
Background. Down syndrome (DS) is the most frequent cause of intellectual disability. In 95% of cases, it is caused by simple trisomy of chromosome 21 resulting from nondisjunction of chromosomes in meiotic division. Currently, the molecular and cellular mechanisms responsible for the phenomenon of nondisjunction are unknown. Objectives. To investigate the incidence of 5 single-nucleotide polymorphisms (SNPs) of the MTHFR gene in a population of Polish mothers who had given birth to children with trisomy 21 in comparison with a control group of women with healthy offspring. Material and methods. The test material comprised venous blood collected from mothers who had given birth to a child with DS (study group, n = 130) as well as from women who had given birth to children without trisomy 21 (control group, n = 88). DNA was isolated using a kit manufactured by Qiagen. Amplification was carried out using a Qiagen Multiplex PCR Kit (Qiagen); genotyping was performed using SNaPshot Genotyping MasterMix (Applied Biosystems). Results. No statistically significant differences were observed in the frequency of genotypes between the examined groups in terms of the polymorphisms of the MTHFR gene. Conclusions. In the Polish population studied, no relationship was found between the occurrence of particular genotypes of the MTHFR gene, i.e., 677CT, 1298AC, rs3737964, rs4846048, and rs1994798, in women and the birth of children with trisomy 21. The results contradict the validity of research on polymorphisms of the MTHFR gene as potential predisposing factors for the occurrence of trisomy 21 in children.
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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