The antimicrobial peptide LL-37
A potential future antibiotic for the treatment of infections with pathogenic Neisseria
Miriam Geörg
Antibiotics used to be a universal remedy for the treatment of bacterial infections. In recent years, however, there has been an alarming increase in infections with pathogens that do not respond to conventional antibiotics anymore. Antimicrobial peptides such as the human LL-37 are promising candidates for the development of new antibacterial compounds against these multi-drug resistant bacteria. As natural effector molecules of the immune system, they play an important role in defending both animals and plants from invading germs. The aim of this study was to analyse the capacity of LL-37 to kill bacteria, in particular pathogenic Neisseria meningitidis (meningococci) and N. gonorrhoeae (gonococci), under conditions that exist in the human host organism. Neisseria causes severe diseases including meningitis, sepsis and the sexually transmitted disease gonorrhoea. The availability of new drugs against resistant strains is therefore essential. It could be shown that LL-37 can kill meningococci effectively at a concentration of only 10 M. At this concentration, LL-37 did not show any toxic effects on human cells, which would be an important prerequisite if LL-37 were to be considered for the medical treatment of Neisseria infections. Furthermore, LL-37 could prevent the attachment of both meningococci and gonococci to human cells of throat or genital tract, a process that would normally be the first step during an infection.
Lipooligosaccharide (LOS) is a surface structure of pathogenic Neisseria and the major component that triggers lethal sepsis in meningococcal infections due to an overstimulation of the immune system. Different meningococcal mutants, with LOS molecules that were shorter than those of the wild-type strain or missing completely, were compared in respect to their susceptibility to LL-37. It could be shown that LOS structure had an influence on bacterial resistance against LL-37. This might be an additional reason for the devastating role of LOS in meningococcal pathogenesis.
Degree project in biology, spring 2006
Examensarbete i biologi, 10p, Uppsala universitet, vår 2006
Biology Education Centre and Department of Medical Biochemistry and Microbiology, Uppsala University
Supervisors: Ann-Beth Jonsson and Allison Jones