Evaluation of the role of polyamine transporters in biofilm formation by Streptococcus pneumoniae and Klebsiella pneumoniae

Abstract

Streptococcus pneumoniae and Klebsiella pneumoniae are human pathogens of great importance, causing more than one million deaths worldwide every year. Both microbes can colonize the human mucosa asymptomatically and may, under certain circumstances, invade sterile niches and cause an array of diseases, including pneumonia, meningitis, liver abscesses and urinary tract infections. S. pneumoniae and K. pneumoniae are also able to form biofilms - an ability that favors colonization and bacterial dispersion, and contributes to the appearance of multi-resistant strains, contributing to increase bacterial virulence during infections. Biofilm formation is intimately associated with quorum sensing and with the production of type 2 auto-inducers (AI-2) molecules. Recent data correlates the presence of polyamines and their transporters with biofilm formation by diverse bacterial species; a reduction in the levels of intracellular polyamines, as well as deletion of genes responsible for polyamine transport has led to an inhibition in biofilm formation by Escherichia coli, Yersinia pestis and Bacillus subtilis. Thus, the present work aims at investigating the role of polyamines and their transporters in biofilm formation and quorum sensing in S. pneumoniae and K. pneumoniae. Mutant strains negative for polyamine transporters will be constructed using CRIPR/Cas9 - a technology that will be standardized in our laboratory - and compared with wild type strains in their ability to communicate through quorum sensing and to form biofilms in vitro and in vivo. Our main goal is to characterize the mechanisms that could inhibit biofilm formation by these pathogens. (AU)