Candidiasis is one of the most common fungal diseases that can pose a threat to life in immunodeficient individuals, particularly in its disseminated form. Not only fungal invasion but also fatal infection-related inflammation are common causes of systemic candidiasis. In this study, we investigated in vitro immunomodulatory properties of the antifungal pea defensin Psd1 upon Candida albicans infection. Using the real-time PCR, we showed that Psd1 inhibited the antimicrobial peptide HBD-2 and pro-inflammatory cytokines IL-1 and IL-8 downregulation at mRNA level in epithelium cells caused by C. albicans infection. By using the Caco-2/immune cells co-culture upon C. albicans infection and the multiplex xMAP assay, we demonstrated that this pathogenic fungus induced a pronounced host defense response; however, the cytokine responses were different in the presence of dendritic cells or monocytes. We revealed that Psd1 at a low concentration (2 µM) had a pronounced immunomodulatory effect on the Caco-2/immune cells co-culture upon fungal infection. Thus, we hypothesized that the pea defensin Psd1 might be an effective agent in the treatment of candidiasis not only due to its antifungal activity, but also owing to its ability to modulate a protective immune response upon infection.
An increase in the frequency of mycoses and spreading of multidrug-resistant fungal pathogens necessitates the search for new antifungal agents. Earlier, we isolated the novel defensin from lentil Lens culinaris seeds, designated as Lc-def, which inhibited the growth of phytopathogenic fungi. Here, we studied an antifungal activity of Lc-def against human pathogenic Candida species, structural stability of the defensin, and its immunomodulatory effects that may help to prevent fungal infection. We showed that Lc-def caused 50% growth inhibition of clinical isolates of Candida albicans, C. krusei, and C. glabrata at concentrations of 25–50 μM, but was not toxic to different human cells. The lentil defensin was resistant to proteolysis by C. albicans and was not cleaved during simulated gastroduodenal digestion. By using the multiplex xMAP assay, we showed for the first time for plant defensins that Lc-def increased the production of such essential for immunity to candidiasis pro-inflammatory cytokines as IL-12 and IL-17 at the concentration of 2 μM. Thus, we hypothesized that the lentil Lc-def and plant defensins in general may be effective in suppressing of mucocutaneous candidiasis due to their antifungal activity, high structural stability, and ability to activate a protective immune response.
According to the World Health Organization, every year about 1 million cases of purulent bacterial meningitis (PBM) are registered in the world, of which 200 thousand cases end in death. Bacterial meningitis is polyethiologic, which makes the task of determining the pathogen the main in the organization of epidemiological surveillance, treatment regimens, planning of preventive and anti-epidemic measures. The quality of laboratory diagnostics has a key influence on this. The true incidence of meningitis of different etiology can be altered at low-efficiency laboratory diagnostics. This work was carried out to assess the effectiveness of existing laboratory methods for the detection of PBM pathogens: Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis; as a part of the programme on sentinel surveillance of invasive bacterial diseases (IBD) carried out by the WHO regional office for Europe in a number of countries in Europe (Ukraine, Belarus), Transcaucasia (Azerbaijan, Armenia, Georgia), Asia (Uzbekistan, Kyrgyzstan, Kazakhstan) in the period 2010-2017. 2893 samples of clinical material (CSF and blood) obtained from patients with the meningeal syndrome were studied by four diagnostic methods: cultural method, latex-agglutination test, immunochromatographic test (BinaxNOW), PCR (conventional and real-time), used to identify the following pathogens: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae. When identifying the causative agents of BM, PCR more effective than culture method is 5 times in detecting N. meningitidis; 3 times in the detection of S. pneumoniae; 4 times the detection of H. influenzae b. Latex-agglutination test and immunochromatographic test allow to increase the identification of pathogens of BM for N. meningitidis - by 35.6%; S. pneumoniae - by 67%; H. influenzae b - by 19.2%, it is possible to set them in the field and at the epidpoint if necessary. When working with clinical material from patients diagnosed with GBM, it is advisable for bacteriological laboratories to complement the culture method of microbiological diagnosis of latex-agglutination test, immunochromatographic test or PCR.
Objective. To investigate a candidemia outbreak caused by C. parapsilosis in a clinical unit of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (NMRC PHOI). Materials and Methods. A total of 35 isolates of C. parapsilosis obtained from clinically significant specimens and swabs, including hands of nursing staff of the NMRS PHOI, over the 2018-2020 were genotyped in this retrospective study. Identification of C. parapsilosis isolates was performed by microbiological methods. The clonal structure of C. parapsilosis isolates was investigated by polymerase chain reaction followed by fragment analysis of microsatellite repeats (short tandem repeats, STR markers). Results. The results of the study showed genetic diversity of the population of C. parapsilosis isolates over the 2018–2020 in the NMRC PHOI. A total of 27 genotypes were identified, one of which caused candidemia in 6 patients. Conclusions. The study results confirmed the nosocomial candidemia outbreak and showed the fragment analysis of STR-markers may be used for epidemiological investigations of outbreaks in hospital settings.
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