An in-silico approach to identify novel antimicrobial peptides against multi-drug resistant Stenotrophomonas maltophilia

Abstract 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.