Antibacterial Activity of Terpene Natural Compounds against Klebsiella pneumoniae: in silico study

Abstract

Klebsiella pneumoniae, a Gram-negative, nonmotile, encapsulated rod-shaped bacterium has become an emerging nosocomial pathogen that can cause clinical infectious diseases. Through the years, frequent use and contact with antibiotics in hospitals have created antibiotic-resistant K. pneumoniae strains, limiting available treatment options for medical intervention against infections. Many proteins support the property of antibiotic resistance and one of these proteins found in Klebsiella bacteria is beta-lactamase SHV-1. Many terpenes are known to be active against a wide variety of microorganisms, including gram-positive and gram-negative bacteria and fungi. Toxic effects on membrane structure and function have been generally used to explain the antimicrobial action of essential oils and their monoterpenoid components. Monoterpene indole alkaloids (MIAs) are compounds that are identified from six genera of the Apocynaceae family. The following genera are Alstonia, Rauvolfia, Kopsia, Ervatamia, Tabernaemontana, and Rhazya. Traditionally, plant species of this family have been used for the treatment of fever, malaria, gastrointestinal ailments, diabetes, and pain. There are many terpenes natural compounds (>400 compounds). Thus, finding the terpene compounds that strongly interact with the targeted protein in K. pneumoniae would serve as a potential strategy to find the most potent compounds. The recent study examined the potential interactions between beta-lactamase (bla SHV-1), a protein that supports antibiotic resistance in Klebsiella, and MIAs from six genera of plants in the Apocynaceae family. The MIAs were used as ligands in this study. The PyRx program for molecular docking and other computer programs were used to assess the effectiveness of MIAs as inhibitors (PyMOL, LigPlot+, Discovery Studio, Notepad, Gimp 2.10). In this study, the initial molecular docking investigation identified several MIAs with potential as inhibitors. Paucidisine, (-)-19-Oxoisoeburnamine, and paucidactine A demonstrated the most promise. Ligand-protein interactions, such as hydrogen bonds and hydrophobic interactions, were also analyzed to determine the best terpenes. The most effective terpenes showed a higher percentage of similarity when compared to native ligands. It is important to note that these findings are based on an in silico study and require in vitro confirmation before being considered for future drug design. Overall, this study takes a significant step toward discovering alternative treatment options for antibiotic-resistant Klebsiella infections. By exploring the potential of MIAs as inhibitors, this research offers a promising avenue for combating antibiotic resistance and improving patient outcomes.