Project description:BACKGROUND:MDR-TB is a major threat to global TB control. In 2015, 580,000 were treated for MDR-TB worldwide. The worldwide roll-out of GeneXpert MTB/RIF® has improved diagnosis of MDR-TB; however, in many countries laboratories are unable to assess drug resistance and clinical predictors of MDR-TB could help target suspected patients. In this study, we aimed to determine the clinical factors associated with MDR-TB in Bamako, Mali. METHODS:We performed a cross-sectional study of 214 patients with presumed MDR-TB admitted to University of Bamako Teaching Hospital, Point-G between 2007 and 2016. We calculated crude and adjusted odds ratios for MDR-TB disease diagnosis using SPSS. RESULTS:We found that age ?40years (OR=2.56. 95% CI: 1.44-4.55), two courses of prior TB treatment (OR=3.25, 95% CI: 1.44-7.30), TB treatment failure (OR=3.82, 95% CI 1.82-7.79), sputum microscopy with 3+ bacilli load (OR=1.98, 95% CI: 1.13-3.48) and a history of contact with a TB patient (OR=2.48, 95% CI: 1.11-5.50) were significantly associated with confirmation of MDR-TB disease. HIV was not a risk factor for MDR-TB (aOR=0.88, 95% CI: 0.34-1.94). CONCLUSION:We identified several risk factors that could be used to identify MDR-TB suspects and prioritize them for laboratory confirmation. Prospective studies are needed to understand factors associated with TB incidence and clinical outcomes of TB treatment and disease.
Project description:MicroRNAs (miRNAs) play important roles by regulating the expression of target genes in plant and animal. However, little known about mechanism of fungal miRNA-like RNAs (milRNAs) regulating target gene restricts their functional exploration. In this study, multiple omics were used to identify the milRNAs and their target genes in a phytopathogenic fungus Valsa mali. Many candidate pathogenic factors were found to be regulated by milRNA-directed cleavage way. Absence or downregulated expression of Vm-milRNAs promote expression of candidate pathogenic factors during V. mali infection. Vm-milR16 is a significantly downregulated milRNA during V. mali infection, resulting in significantly upregulated expression of three target genes: VmSNF1, VmDODA, and VmHy1. Overexpression of Vm-milR16 significantly reduces the pathogenicity of V. mali. And all the three target genes of Vm-milR16 are required for the full pathogenicity of V. mali. Further analysis revealed that VmSNF1 regulates the pathogenicity by affecting the expression of pectinase genes during V. mali infection. And all the three target genes are essential for oxidative stress response during V. mali-host interaction. Vm-milRNAs may help V. mali to intelligently use limited resources and adaptively regulate pathogenicity by enhancing expression of pathogenic factors and fitness during infection.
Project description:In order to explore the role of LaeA in secondary metabolite biosynthetic gene clusters’ regulation, toxin production, and virulence of Valsa mali, TMT-based proteomic analysis of wildtype, LaeA deletion mutant and overexpression mutant were performed. Totally, 4,299 proteins (FDR < 0.01) were identified by searching against the Valsa mali protein sequence database.