In silico analysis on binding action of beta-lactam drugs against TEM and SHV class A beta-lactamases from Klebsiella pneumoniae

• Published in: Discover applied sciences 2024-04, Vol.6 (4), p.196, Article 196
• Main Authors: Akinola, Omowumi Temitayo, Oyebamiji, Abel Kolawole, Oke, David Gbenga, Adekunle, David O., Olanrewaju, Adesoji Alani, Akintelu, Sunday Adewale
• Format: Article
• Language: English
• Subjects: Affinity; Amides; Amino acids; Amoxicillin; Annotations; Antibiotic resistance; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; Binding; Binding sites; Cefepime; Ceftazidime; Clavulanic acid; Deoxyribonucleic acid; DNA; Docking; Drug resistance; Enzyme inhibitors; Enzymes; Gene sequencing; Genomes; Gram-negative bacteria; Hospital wastes; Hydrogen bonds; Inhibitors; Klebsiella; Klebsiella pneumoniae; Medical wastes; Meningitis; Meropenem; Nosocomial infection; Penicillin; Pneumonia; Urinary tract; Whole genome sequencing; β Lactamase; β-Lactam antibiotics
• ISSN: 3004-9261; 2523-3963; 3004-9261; 2523-3971
• DOI: 10.1007/s42452-024-05783-8

One of the leading Gram-negative bacteria that causes nosocomial illnesses such as pneumonia, urinary tract infections, meningitis, etc. is Klebsiella pneumoniae . Conventionally, K. pneumoniae infections are treated with beta-lactam (β-lactam) based antibiotics like penicillin; however, these treatments are becoming less and less successful as the bacterium generates various kinds of beta-lactamases (β-lactamases) to inactivate the medicines. In the present study, whole genome sequencing was used to obtain class A β-lactamase from an isolate that showed antibiotic resistance using the disk diffusion method. Class A β-lactamase, TEM and SHV obtained from the isolate were used for docking. We downloaded the structure of two enzymes (amino acids) (TEM and SHV background) from Protein DataBank (PDB) with PDB IDs: 1n9b and 2zd8. The structures of the β-lactams antibiotics (ceftazidime, cefepime, Amoxicillin clavulanic acid, and meropenem) were drawn using Chemsketch. The interactions of the inhibitors with several β-lactams antibiotics were studied after docking using Autodock software. The docking results showed that of all the five drugs docked with the enzymes (inhibitors), cefepime excelled in terms of ability to bind well against both the TEM and SHV enzymes. This was shown with the binding affinity against 1n9b and 2zd8 being − 8.23996162 and − 8.5358305 respectively, as such making it the best β-lactam antibiotic against TEM and SHV of all the five drugs.