Análise proteômica e estudo do mecanismo de ação de peptídeo sintético antimicrobiano contra Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae is an opportunistic human pathogenic microorganism that in many cases is related to a wide variety of infections. Furthermore, it has been recognized, along with other microorganisms, for developing mechanisms of resistance against antibiotics. In order to deal with antibacterial resistance, potential alternative molecules are being studied, such as synthetic peptides. Mo-CBP3-PepI has shown activity against K. pneumoniae, with a 50% minimum inhibitory concentration (MIC50) of 50 µg mL-1. The present work aimed to study the mechanisms of action of the peptide Mo-CBP3-PepI against K. pneumoniae. Together, fluorescence microscopy analysis and proteomics analysis revealed alteration in cell membrane permeability and overproduction of ROS. The protein profile of cells treated with Mo-CBP3-PepI showed drastic changes in essential metabolic pathways. After treatment of K. pneumoniae cells with Mo-CBP3-PepI, a reduction in the abundance of proteins related to energy metabolism, DNA and protein metabolism, cytoskeleton and cell wall organization and pathogenesis was observed. Such a reduction leads to energy deficit, inhibition of DNA replication and inhibition of cell wall renewal leading to the cell. In addition, the high accumulation of proteins and pro-apoptosis, and proteins are involved in DNA damage. Thus, these results revealed that Mo-CBP3-PepI acts by causing membrane and cell wall damage and induces cell death in K. pneumoniae cells by increasing ROS levels, as well as proteins that induce cell death. Such a molecule presents mechanisms of action that hinder the development of resistance mechanisms, and may be a potential molecule for the development of drugs.