Investigation of the potential of viral depolymerases for use in alternative treatment of infections caused by Klebsiella pneumoniae

• Grant number: 24/14407-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Henrique Ferreira
• Grantee: Ana Carolina dos Santos Mendes Lemos
• Host Institution: Instituto de Biociências (IB). Universidade Estadual Paulista (UNESP). Campus de Rio Claro. Rio Claro , SP, Brazil
• Associated research grant: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center, AP.CEPID

Abstract

The development of antibiotic resistance in microorganisms is one of the main global health problems according to the World Health Organization. Among the main bacteria responsible for opportunistic infections and acquired pneumonia is Klebsiella pneumoniae. K. pneumoniae is a Gram-negative bacterium that can be resistant to carbapenems, which are used to combat bacteria that produce ²-lactamases. In addition, K. pneumoniae produces biofilm, extracellular polymeric substances (EPS) that act as a protective layer, defending cells against phagocytosis and the action of antimicrobial compounds. Biofilm is therefore a crucial structure for bacterial virulence and represents a potential target for the development of antibacterials. Bacteriophages are viruses that infect bacteria and use the production of polysaccharide depolymerases in their tails as an infection strategy. These enzymes degrade the EPS and facilitate viral adsorption on the bacterial surface at the beginning of the invasion process of the bacterial host. Therefore, depolymerases could be promising biotechnological tools as an alternative method to combat K. pneumoniae. In this work, we will try to isolate bacteriophage genes that encode depolymerases and build expression systems for the heterologous production of these enzymes in bacteria. Subsequently, these enzymes will be purified for biochemical characterization and evaluation of their potential as EPS-degrading agents, aiming at an alternative treatment for infections caused by Klebsiella pneumoniae.