Antimicrobial peptides (AMPs) are important components of the innate immune system and considered as potential therapeutic molecules for drug-resistant bacteria. AMPs have a rapid bactericidal mode of action and can interact with a range of targets. Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen associated with various clinical syndromes, including respiratory infections in immunocompromised patients and people with a history of diseases such as cystic fibrosis (CF) or cancer. A broad spectrum of antibiotics has limited sensitivity to this bacterium. Therapeutic options for treating S. maltophilia are limited due to the bacterium's low resistance to antibiotics, mainly based on genes encoding antibiotic-inactivating enzymes and MDR efflux pumps on the chromosome. Peptide-based antimicrobial drugs could be viable to combat antibiotic resistance as they have many advantages, including rapid microbicidal activity against S. maltophilia. A total of 235 peptide sequences from UniProtKB predicted to have activity against Gram-negative bacteria using DBAASP were screened for toxicity and hemolytic activity. Eighty-one peptides that are non-toxic and non-hemolytic were selected considering their physiochemical properties such as aliphatic index, pI value, and GRAVY. The peptides were docked to the L1 beta-lactamase present in S. maltophilia. After successful docking, the complex with the highest binding affinity for molecular dynamics GROMACS was taken to investigate the stability of the complex. The results showed that the AMPs were bound to the active site with good affinity. The active site containing zinc atoms was masked so that the zinc atoms were no longer available for the catalytic role of the enzyme.
Antibiotic resistance is threatening the medical industry in treating microbial infections. Many organisms are acquiring antibiotic resistance because of the continuous use of the same drug. Gram-negative organisms are developing multi-drug resistance properties (MDR) due to chromosomal level changes that occurred as a part of evolution or some intrinsic factors already present in the organism. Stenotrophomonas maltophilia falls under the category of multidrug-resistant organism. WHO has also urged to evaluate the scenario and develop new strategies for making this organism susceptible to otherwise resistant antibiotics. Using novel compounds as drugs can ameliorate the issue to some extent. The β-lactamase enzyme in the bacteria is responsible for inhibiting several drugs currently being used for treatment. This enzyme can be targeted to find an inhibitor that can inhibit the enzyme activity and make the organism susceptible to β-lactam antibiotics. Plants produce several secondary metabolites for their survival in adverse environments. Several phytoconstituents have antimicrobial properties and have been used in traditional medicine for a long time. The computational technologies can be exploited to find the best compound from many compounds. Virtual screening, molecular docking, and dynamic simulation methods are followed to get the best inhibitor for L1 β-lactamase. IMPPAT database is screened, and the top hit compounds are studied for ADMET properties. Finally, four compounds are selected to set for molecular dynamics simulation. After all the computational calculations, withanolide R is found to have a better binding and forms a stable complex with the protein. This compound can act as a potent natural inhibitor for L1 β-lactamase.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.