In vivo and in vitro studies of the adhesion and invasion of host cells by a fimbriae-deficient mutant strain of Klebsiella pneumoniae

Abstract

Iron is an essential nutrient for most microorganisms and it has an important role in cellular metabolism and in the regulation of virulence genes expression in pathogenic bacteria. This regulation is mediated by the transcriptional regulator Fur. Fur forms a complex with ferrous ion and this complex binds to specific sequences, called Fur boxes, located on the promoter region of target genes leading to the transcriptional induction or repression of these genes. Klebsiella pneumoniae is a gram-negative opportunistic pathogen whose main infection sites are the gastrointestinal tracts, respiratory and genitourinary systems. Among gram-negative pathogens K. pneumoniae is the second most common agent in septicemia and is the second leading cause of urinary tract infections. Cell-surface components are the main virulence factors of K. pneumoniae, specially the expression of type 1 fimbriae adhesive. These fimbriae play a crucial role in the genitourinary tract infection, since they promote adhesion of the bacteria and invasion of bladder cells. The synthesis of fimbriae in K. pneumoniae is regulated by fimK and fimZ genes. Unlike fimK gene, whose role in the regulation of fimbrial expression and biofilm formation is well characterized, little is known about the role of fimZ gene. Preliminary results indicated a Fur box on the promoter region of fimZ gene, thus revealing that the fimbrial expression may be regulated by Fur regulator. In this sense, this project aims to investigate the role of fimZ gene on the expression regulation of type 1 fimbriae in Klebsiella pneumoniae and the effects of iron, through the Fur repressor, in the process of adhesion and invasion of host cells. (AU)