Influence of the polysaccharide capsule on biofilm formation and virulence in Klebsiella pneumoniae

• Grant number: 24/02517-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Thiago Rojas Converso
• Grantee: Maria Eduarda Souza Guerra
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Klebsiella pneumoniae is a bacterium commonly associated with infections acquired in a hospital environment, such as urinary infections, pneumonias, bacteremia, and septicemia. Among the various virulence factors that the pathogen presents, the polysaccharide capsule stands out, which favors immune evasion and is associated with the hypervirulence phenotype. Another important virulence mechanism in K. pneumoniae is its ability to form biofilms, a process regulated by quorum sensing-a complex communication network between bacteria through signaling molecules called self-inducers, which favor colonization and survival in stressful environments. The presence of the capsule and the formation of biofilms are associated with greater resistance to the action of antibiotics and host defense molecules, such as antimicrobial peptides (AMPs). In addition, the capsule seems to influence the formation of biofilms, but the mechanisms involved in this effect are not fully elucidated. Thus, the present project aims to investigate the role of the polysaccharide capsule in the formation of biofilms, in communication via quorum sensing and in the resistance of K. pneumoniae to MPAs, as well as its correlation with the pathogenicity of the bacterium in a murine model. For this, biofilm formation assays will be carried out in vitro and in situ and in vivo, comparing wild bacteria and their isogenic mutant that does not produce capsules. The bacteria will also be compared for their ability to adhere and invade respiratory and urinary epithelium cells, which represent two important sites of infection. The production of type 2 self-inducing molecules (related to quorum sensing) will be measured, and the expression of genes related to the formation of biofilms will be measured. Finally, the resistance of wild and mutant bacteria to death by peptides of the catelicidin family, which correspond to an important defense mechanism against infections, will be investigated. The results of this study should contribute to the elucidation of the role of the capsule for the pathogenicity of the bacterium, favoring the development of future therapeutic or prophylactic strategies against this pathogen.