Aim: To evaluate the activity of (-)-camphene-based thiosemicarbazide (TSC) and 4-hydroxy-thiosemicarbazone (4-OH-TSZ), alone and in combination against Gram-positive. Material & methods: MIC were determined for Staphylococcus aureus, Enterococcus spp. reference strains and clinical isolates. Drug combination, time–kill and cytotoxicity assays were also performed. Results: TSC and 4-OH-TSZ demonstrated potent inhibitory activity against S. aureus and Enterococcus spp., including multidrug-resistant isolates (MIC ranging from 1.9 to 31.2 μg/ml), and were bactericidal for the reference strains of both Gram-positive tested. The derivatives proved to be selective for the bacteria and synergistic with oxacillin and vancomycin. Conclusion: (-)-Camphene-based derivatives can represent promising drug candidates against critical pathogens, such as S. aureus and Enterococcus spp., including MRSA and vancomycin resistance Enterococcus spp. isolates.
Yeasts of the genera Candida and Saccharomyces are opportunist pathogens and cause oral lesions, especially in immunocompromised patients. This study assessed yeasts isolated from chronic kidney patients undergoing haemodialysis for their adhesion capacity, biofilm formation and susceptibility to antifungal agents. Ten isolates of Candida spp. and one isolate of Saccharomyces cerevisiae were tested for adhesion to buccal epithelial cells (BECs), adhesion and formation of biofilm in artificial saliva and their susceptibility profile to antifungal agents. Adhesion and biofilm formation were undertaken in polystyrene plates with artificial saliva, whilst susceptibility to antifungal agents was evaluated by broth microdilution. Candida parapsilosis had the highest adhesion index in BECs (154.55 ± 22.13) and Candida rugosa was the species with the highest adhesion capacity (18 398 Abs cm(-2)) in abiotic surface with artificial saliva. Candida albicans provided the greatest biofilm formation (2035 Abs cm(-2) ± 0.09) but was revealed to be susceptible to the five antifungal agents under analysis. However, some non-albicans Candida isolates showed a lower susceptibility for the antifungal agents itraconazole, fluconazole and voriconazole. All of the species were sensitive to amphotericin B and nystatin. The current analysis showed that yeasts isolated from the mouth of chronic kidney patients undergoing haemodialysis varied significantly with regard to their capacity for adherence, biofilm formation and susceptibility to antifungal agents, underscoring the high virulence of non-albicans Candida species.
Aim: To elucidate the changes in protein expression associated with polymyxin resistance in Klebsiella pneumoniae, we profiled a comparative proteomic analysis of polymyxin B-resistant mutants KPC-2-producing K. pneumoniae, and of its susceptible counterparts. Material & methods: Two-dimensional reversed phase nano ultra-performance liquid chromatography mass spectrometry was used for proteomic analysis. Results: Our results showed that the proteomic profile involved several biological processes, and we highlight the downregulation of outer membrane protein A (OmpA) and the upregulation of SlyB outer membrane lipoprotein (conserved protein member of the PhoPQ regulon) and AcrA multidrug efflux pump in polymyxin B-resistant strains. Conclusion: Our results highlight the possible participation of the SlyB, AcrA and OmpA proteins in the determination of polymyxin B heteroresistance in KPC-2-producing K. pneumoniae.
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