High diversity of yeast species and strains responsible for vulvovaginal candidiasis in South-East Gabon.

OBJECTIVES: Candida albicans generally remains the principal pathogenic yeast responsible for vulvovaginal candidiasis (VVC), although with variable prevalence. In this study, we evaluated the evolution of the prevalence of the non-Candida albicans Candida (NCAC) species and investigated the genotypic diversity and the population genetic structure of the circulating C. albicans strains associated with VVC in the vicinity of Franceville (Gabon). METHODS: A total of 110 independent isolates were identified using both MALDI-TOF MS and conventional techniques. The population genetic structure of the C. albicans strains was determined by multiple locus variable-number tandem repeat analysis using 4 microsatellite markers. RESULTS: The mean and median age of the patients was 31 years. Seven patients had a mixed infection. C. albicans accounted for 62 % (n=68) of the total isolates. NCAC were dominated by C. glabrata, followed by P. kudriavzevii, C. parapsilosis, C. tropicalis, M. guilliermondii, and C. nivariensis. The cluster analysis revealed a high diversity, with a total of 50 different genotypes. The most represented genotype was shared by only four strains, while the vast majority (39 strains) had a unique MLVA pattern. Geographic clusters were not detected. CONCLUSION: The study provides information on species distribution and possible changing epidemiology while reporting for the first time C. nivariensis in VVC in Africa. This study is also the first to investigate the genotypic diversity of the circulating C. albicans strains associated with VVC in Central Africa. Such analyses would help understand the molecular epidemiology of C. albicans.

Vulvovaginal candidiasis among symptomatic women of childbearing age attended at a Medical Analysis Laboratory in Franceville, Gabon.

BACKGROUND: Vulvovaginal candidiasis (VVC) is one of the most common lower genital tract infections in women; this unpleasant and extremely embarrassing pathology is one of the main reasons for gynaecological consultation. In Gabon, the prevalence of VVC remains poorly described even though VVC is known to be the leading gynaecological condition in several countries. This retrospective cross-sectional study sought to assess the prevalence of VVC among symptomatic women in southeastern Gabon. METHODS: Clinical samples were collected from patients suspected to have VVC during a 2-year period (from January 2016 to December 2017). Gram staining of vaginal smears provided indications of vaginal flora and confirmed the presence of yeast. Sabouraud-chloramphenicol and chromID Candida media were used to isolate yeast, and species identification was performed using morphological tests and the Vitek 2 Compact automated system. RESULTS: For the 873 patients included in this study, the prevalence of VVC was 28.52%. Eleven Candida species were identified, with greater representation of Candidaalbicans (82.73%) than of Non C. albicanscandida (NCAC) (17.27%), which were distributed as follows: Candidafamata (4.02%), Candida spp. (3.61%), Candidarugosa (3.21%), Candidalipolytica (1.61%), Candidaparapsilosis (1.61%), Candidaglabrata (1.21%), Candidatropicalis (0.80%), Candidakrusei (0.40%), Candidadubliniensis (0.40%), and Candidasphaerica (0.40%). CONCLUSION: This study offers the first estimation of VVC among Gabonese women in childbearing age with the symptoms. It showed that VVC is very common in Gabon. C. albicans as the most commonly represented species.

Diagnostic and therapeutic potential of tetanus toxin-derivatives in neurological diseases.

We assessed the ex vivo reactivity of peptidic constructs of Tet1 (analog of tetanus toxin non-virulent C fragment) with sequence homology to the cysteine-active site of thioredoxin (Tet1THO) or tetralysine (Tet1PLYS) with oxidative species or axonopathic sodium cyanate (NaOCN), respectively. We then assessed their neuronal uptake in vivo in laboratory animals. The reactivity of Tet1PLYS with NaOCN (1:2.5 to 1:37.5 molar ratios) or Tet1THO with hydrogen peroxide (1:0.4 to 1:6.2 molar ratios) was assessed by mass spectrometry. Green fluorescence protein (GFP)-tagged Tet1-derivatives (3 mg/ml in artificial cerebrospinal fluid) were administered daily to rats by intramuscular injection in latissimus dorsi at lumborum at the dose of 1 µl/g of body weight, for 3 days. Motor neuron uptake was assessed after double immunolabeling for GFP and choline acetyltransferase. Mass spectrometry analysis successfully demonstrated the ex vivo reactivity of Tet1-derivatives in a concentration-dependent manner. Confocal microscopy revealed the localization of Tet1-derivatives in axons and motor neuron cell bodies. Intramuscular delivery of Tet1-derivatives appears to be a practical approach to circumvent the blood nerve barrier and selectively deliver small molecules to the nervous system, for diagnostic and/or treatment purposes.

Proximal giant neurofilamentous axonopathy in mice genetically engineered to resist calpain and caspase cleavage of α-II spectrin.

We use 1,2-diacetylbenzene (1,2-DAB) to probe molecular mechanisms of proximal giant neurofilamentous axonopathy (PGNA), a pathological hallmark of amyotrophic lateral sclerosis. The spinal cord proteome of rodents displaying 1,2-DAB PGNA suggests a reduction in the abundance of α-II spectrin (Spna2), a key protein in the maintenance of axonal integrity. Protein immunoblotting indicates that this reduction is due to Spna2 degradation. We investigated the importance of such degradation in 1,2-DAB PGNA. Spna2 mutant mice lacking a calpain- and/or caspase-sensitive domain (CSD), thus hypothetically resistant to 1,2-DAB, and wild-type littermates, were treated with 1,2-DAB, 35 mg/kg/day, or saline control, for 3 weeks. 1,2-DAB induced motor weakness and PGNA, irrespective of the genotype. Spna2-calpain breakdown products were not detected in mutant mice, which displayed a normal structure of the nervous system under saline treatment. Intriguingly, treatment with 1,2-DAB reduced the abundance of the caspase-specific 120-kDa Spna2 breakdown products. Our findings indicate that degradation of Spna2 by calpain- and/or caspase is not central to the pathogenesis of 1,2-DAB axonopathy. In addition, the Spna2-CSD seems to be not required for the maintenance of the cytoskeleton integrity. Our conceptual framework offers opportunities to study the role of calpain-caspase cross talk, including that of the protease degradomics, in models of axonal degeneration.