Synergistic antifungal activity and potential mechanism of action of a glycolipid-like compound produced by Streptomyces blastmyceticus S108 against Candida clinical isolates.

AIM: The present study aimed to investigate a novel antifungal compound produced by Streptomyces blastmyceticus S108 strain. Its effectiveness against clinical isolates of Candida species and its synergistic effect with conventional antifungal drugs were assessed, and its molecular mechanism of action was further studied against Candida albicans. METHODS AND RESULTS: A newly isolated strain from Tunisian soil, S. blastmyceticus S108, showed significant antifungal activity against Candida species by well diffusion method. The butanolic extract of S108 strain supernatant exhibited the best anti-Candida activity with a minimal inhibitory concentration (MIC) value of 250 µg ml-1, determined by the microdilution method. The bio-guided purification steps of the butanolic extract were performed by chromatographic techniques. Among the fractions obtained, F13 demonstrated the highest level of activity, displaying a MIC of 31.25 µg ml-1. Gas chromatography-mass spectrometry and electrospray ionization mass spectrometry analyses of this fraction (F13) revealed the glycolipidic nature of the active molecule with a molecular weight of 685.6 m/z. This antifungal metabolite remained stable to physicochemical changes and did not show hemolytic activity even at 4MIC corresponding to 125 µg ml-1 toward human erythrocytes. Besides, the glycolipid compound was combined with 5-flucytosine and showed a high synergistic effect with a fractional inhibitory concentration index value 0.14 against C. albicans ATCC 10231. This combination resulted in a decrease of MIC values of 5-flucytosine and the glycolipid-like compound by 8- and 64-fold, respectively. The examination of gene expression in treated C. albicans cells by quantitative polymerase chain reaction (qPCR) revealed that the active compound tested alone or in combination with 5-flucytosine blocks the ergosterol biosynthesis pathway by downregulating the expression of ERG1, ERG3, ERG5, ERG11, and ERG25 genes. CONCLUSION AND IMPACT OF THE STUDY: The new glycolipid-like compound, produced by Streptomyces S108 isolate, could be a promising drug for medical use against pathogenic Candida isolates.

[Cryptosporidium infection in patients with major histocompatibility complex class II deficiency syndrome in Tunisia: description of five cases]. / La cryptosporidiose chez les enfants atteints de déficits immunitaires primitifs par défaut d'expression de protéines du complexe majeur d'histocompatibilité classe II en Tunisie : à propos de 5 observations.

BACKGROUND: In Tunisia, Cryptosporidium is frequently identified in diarrheic stools of children and immunocompromised patients. The infection is usually self-limited in immunocompetent populations, but can be severe and life-threatening in immunocompromised individuals. Cryptosporidiosis is well-documented in patients with the human immunodeficiency virus; however, few data are available concerning children with primary immunodeficiencies (PIDs). PATIENTS AND METHODS: A retrospective study was conducted on 5 cryptosporidiosis cases diagnosed in 11 children with PIDs. Cryptosporidium was systematically investigated when patients presented chronic diarrhea. Stool samples were examined for the parasite oocysts by modified Ziehl-Neelsen staining, and DNA was systematically extracted for a nested polymerase chain reaction (PCR). The species were identified by the analysis of restriction patterns. Epidemiological and clinicobiological data were presented for each patient. RESULTS: All cryptosporidiosis cases presented a CMH class II deficiency syndrome. Chronic diarrhea was associated with failure to thrive in all cases. PCR provided the diagnosis in all patients, while Ziehl-Neelsen staining revealed Cryptosporidium oocysts in only 3 cases. Species identification yielded Cryptosporidium hominis in 2 cases, Cryptosporidium meleagridis in 1 case, and Cryptosporidium parvum in 1 case; a C. hominis/C. meleagridis co-infection was observed in the last case. C. hominis was isolated in children from rural areas, suggesting that the infection could have been contracted in the hospital and thus a probability of nosocomial transmission. One of the C. hominis carriers developed sclerosing cholangitis with a high parasite load. CONCLUSION: Cryptosporidiosis with serious clinical symptoms is observed in PID patients, particularly those with CMH class II deficiency syndrome. Early, regular, and repeated screening, improved by PCR, is recommended in this group of patients. The predominance of C. hominis, the anthropophilic species, in children from rural areas should emphasize hygiene measures in care centers where PID cases are treated.

[Microsporidia and cryptosporidia coinfection in an HIV-infected newborn]. / Co-infection par des microsporidies et des cryptosporidies chez un nouveau-né infecté par le VIH.

Microsporidiosis and cryptosporidiosis are emerging opportunistic infections responsible for intestinal manifestations that are often severe in immunocompromised patients. A case of microsporidiosis-cryptosporidiosis coinfection is reported in an HIV-infected newborn. The patient was a 17-day-old female, exclusively breastfed and with no contact with animals. Microsporidiosis and cryptosporidiosis were diagnosed after systematic screening in stool samples using both specific staining and PCR. Two species of microsporidia, Encephalitozoon intestinalis and Enterocytozoon bieneusi, and Cryptosporidium hominis were identified. The contamination of the newborn probably resulted from direct human-to-human transmission during close contact with the mother (who had diarrhea and refused stool sampling). This report highlights the usefulness of the screening of intestinal microsporidiosis and cryptosporidiosis in HIV-infected subjects for better management.

[Research on Parvovirus B19 infections and chronic articular manifestations in a Tunisian hospital]. / Recherche du Parvovirus B19 dans les manifestations articulaires chroniques en milieu hospitalier tunisien.

Parvovirus B19 infection is often associated with acute and chronic joint diseases thus suggesting an etiologic role for the virus in these pathologies. In this work, we looked for a possible correlation between Parvovirus B19 infection and certain types of chronic inflammatory rheumatisms. We therefore, screened a population of 100 patients with different chronic inflammatory rheumatismal affections for serological markers of Parvovirus B19 infection. All patients were Tunisians of both sexes, who presented at the service of Rheumatology of the Charles Nicolle Hospital, Tunis. One hundred blood donors were taken as controls. Specific Immunoenzyme Assays of the ELISA type (Biotrin International, France) were used to detect anti-Parvovirus IgG and IgM. On the other hand, viral DNA was sought by nested PCR in synovial fluid from 14 patients. The data obtained indicate that specific anti-Parvovirus B19 IgG was detectable in the sera of 80.7% of patients and 43% of controls. In contrast, none of the sera was found positive for specific IgM antibodies. Synovial fluid samples could be collected from 14 anti-Parvovirus B19 seropositive patients and were tested for the presence of viral DNA. None of the samples was found positive. The results of our serological study reinforce the hypothesis that Parvovirus B19 infection is associated with rheumatismal joint affections. However, the lack of detectable viral DNA in synovial fluid of the tested seropositive patients points to an indirect role of the virus in these joint disorders.