Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates
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ABSTRACT:
SUBMITTER: Shah M
PROVIDER: S-EPMC10556700 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:The Prevotella genus is a normal constituent of the oral microbiota, and is commonly isolated from mechanically treated polymicrobial infections. However, antibiotic treatment is necessary for some patients. This study compared the antibiotic susceptibility and the presence of resistance genes in clinical oral isolates of P. intermedia, P. nigrescens, and P. melaninogenica. Antibiotic susceptibility was assessed using the agar dilution method. PCR confirmed the species and resistance gene frequency in the Prevotella species. The frequencies of species P. intermedia, P. nigrescens, and P. melaninogenica were 30.2%, 45.7%, and 24.1%, respectively. No isolates of P. intermedia were resistant to amoxicillin/clavulanic acid, tetracycline, or clindamycin. P. nigrescens and P. melaninogenica were resistant to amoxicillin/clavulanic acid and tetracycline at frequencies of 40% and 20%, respectively. P. intermedia was resistant to metronidazole at a frequency of 30%, P. nigrescens at 20%, and P. melaninogenica at 40%. P. nigrescens and P. melaninogenica were resistant to 50% and 10% clindamycin, respectively. The gene most frequently detected was tetQ, at 43.3%, followed by tetM at 36.6%, blaTEM at 26.6%, ermF at 20%, cfxA, cfxA2, and nimAB at 16.6%, and nimAEFI at 3.3%. P. nigrescens was the species with the highest resistance to antibiotics such as amoxicillin/clavulanic acid, amoxicillin, and clindamycin, in addition to being the species with the largest number of genes compared to P. intermedia and P. melaninogenica.
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Project description:Oral lichen planus (OLP) is a common oral mucosal disease, of which the etiology and pathogenesis are still unclear. Microorganisms may play an essential role in the pathogenesis of OLP. Previous studies of our group found that the composition ratio of Prevotella melaninogenica (Pm) on the buccal mucosa surface of OLP patients increased significantly. In addition, Pm could invade the epithelium of OLP. As the first physical defense of the oral mucosa, oral keratinocytes may interact directly with Pm in OLP. Therefore, this study aimed to explore the impact of Pm on primary human oral keratinocytes' transcriptome.
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Project description:BackgroundKlebsiella pneumoniae, a gram-negative bacterium in the Enterobacteriaceae family, is non-motile, encapsulated, and a major cause of nosocomial infections, particularly in intensive care units. The bacterium possesses a thick polysaccharide capsule and fimbriae, which contribute to its virulence, resistance to phagocytosis, and attachment to host cells. The bacterium has developed serious resistance to most antibiotics currently in use.ObjectiveThis study aims to investigate the structural properties of MurI (glutamate racemase) from Klebsiella pneumoniae and to identify potential candidate inhibitors against the protein, which will help in the development of new strategies to combat the infections related to MDR strains of Klebsiella pneumoniae.MethodsThe 3D structure of the protein was modelled using SWISS-MODEL, which utilizes the homology modelling technique. After refinement, the structure was subjected to virtual high throughput screening on the TACC server using Enamine AC collection. The obtained molecules were then put through various screening parameters to obtain promising lead candidates, and the selected molecules were then subjected to MD simulations. The data obtained from MD simulations was then assessed with the help of different global dynamics analyses. The protein-ligand complexes were also subjected to MM/PBSA-based binding free energy calculation using the g_mmpbsa program.ResultsThe screening parameters employed on the molecules obtained via virtual screening from the TACC server revealed that Z1542321346 and Z2356864560 out of four molecules have better potential to act as potential inhibitors for MurI protein. The binding free energy values, which came out to be -27.26±3.06 kcal/mol and -29.53±4.29 kcal/mol for Z1542321346 and Z2356864560 molecules, respectively, favoured these molecules in terms of inhibition potential towards targeted protein.ConclusionThe investigation of MurI via computational approach and the subsequent analysis of potential inhibitors can pave the way for developing new therapeutic strategies to combat the infections and antibiotic resistance of Klebsiella pneumoniae. This study could significantly help the medical fraternity in the treatment of infections caused by this multidrug-resistant pathogen.
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