Acute kidney injury (AKI) following snakebite is common in developing countries and Bothrops genus is the main group of snakes in Latin America. To evaluate the pathogenic mechanisms associated with Bothrops venom nephrotoxicity, we assessed urinary and blood samples of patients after hospital admission resulting from Bothrops snakebite in a prospective cohort study in Northeast Brazil. Urinary and blood samples were evaluated during hospital stay in 63 consenting patients, divided into AKI and No-AKI groups according to the KDIGO criteria. The AKI group showed higher levels of urinary MCP-1 (Urinary monocyte chemotactic protein-1) (median 547.5 vs. 274.1 pg/mgCr; p = 0.02) and urinary NGAL (Neutrophil gelatinase-associated lipocalin) (median 21.28 vs. 12.73 ng/mgCr; p = 0.03). Risk factors for AKI included lower serum sodium and hemoglobin levels, proteinuria and aPTT (Activated Partial Thromboplastin Time) on admission and disclosed lower serum sodium (p = 0.01, OR = 0.73, 95% CI: 0.57–0.94) and aPTT (p = 0.031, OR = 26.27, 95% CI: 1.34–512.11) levels as independent factors associated with AKI. Proteinuria showed a positive correlation with uMCP-1 (r = 0.70, p < 0.0001) and uNGAL (r = 0.47, p = 0.001). FENa (Fractional Excretion of sodium) correlated with uMCP-1 (r = 0.47, P = 0.001) and uNGAL (r = 0.56, p < 0.0001). sCr (serum Creatinine) showed a better performance to predict AKI (AUC = 0.85) in comparison with new biomarkers. FEK showed fair accuracy in predicting AKI (AUC = 0.92). Coagulation abnormality was strongly associated with Bothrops venom-related AKI. Urinary NGAL and MCP-1 were good biomarkers in predicting AKI; however, sCr remained the best biomarker. FEK (Fractional Excretion of potassium) emerged as another diagnostic tool to predict early AKI. Positive correlations between uNGAL and uMCP-1 with proteinuria and FENa may signal glomerular and tubular injury. Defects in urinary concentrations highlighted asymptomatic abnormalities, which deserve further study.
Aims Dinoponera quadriceps venom (DqV) was examined to evaluate the antibacterial activity and its bactericidal action mechanism against Staphylococcus aureus. Methods and Results DqV was tested against a standard strain of methicillin‐sensitive Staphylococcus aureus (MSSA), Staph. aureus ATCC 6538P and two standard strains of methicillin‐resistant Staphylococcus aureus (MRSA), Staph. aureus ATCC 33591 and Staph. aureus CCBH 5330. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the rate of kill and pH sensitivity of the DqV were determined by microdilution tests. Bactericidal and inhibitory concentrations of DqV were tested to check its action on Staph. aureus membrane permeability and cell morphology. The MIC and MBC of DqV were 6·25 and 12·5 μg ml−1 for Staph. aureus ATCC 6538P, 12·5 and 50 μg ml−1 for Staph. aureus CCBH 5330 and 100 and 100 μg ml−1 for Staph. aureus ATCC 33591, respectively. Complete bacterial growth inhibition was observed after 4 h of incubation with the MBC of DqV. A lowest MIC was observed in alkaline pH. Alteration in membrane permeability was observed through the increase in crystal violet uptake, genetic material release and morphology in atomic force microscopy. Conclusions The results suggest antibacterial activity of DqV against Staph. aureus and that the venom acts in the cell membrane. Significance and Impact of the Study Alteration in membrane permeability may be associated with the antimicrobial activity of hymenopteran venoms.
1 November 2019 in Diagnostic Microbiology and Infectious Disease
Aims Violacein (VIO), a bacterial pigment produced by Chromobacterium violaceum, was examined to evaluate the antichagasic activity and its action mechanism against Trypanosoma cruzi Y strain. Methods and Results Violacein was tested against the epimastigote, trypomastigote and amastigote forms of T. cruzi Y strain (benznidazole‐resistant strain). VIO inhibited all T. cruzi developmental forms, including amastigotes, which is implicated in the burden of infection in the chronic phase of Chagas disease (CD). VIO induced cell death in T. cruzi through apoptosis, as determined by flow cytometry analyses with specific molecular probes and morphological alterations, such as involvement of reactive oxygen species and changes in mitochondrial membrane potential and cell shrinkage. Conclusion The results suggest antichagasic activity of VIO against T. cruzi Y strain with apoptotic involvement. Significance and Impact of the Study The treatment of CD has limited efficacy and side effects that restrict patient tolerability and compliance. The VIO molecule could be used as a model for therapeutic alternatives for this disease.