Abstract:
Widespread use of antibiotics has increased antibiotic resistance among pathogenic bacteria. Approximately 70% of infection-causing bacteria in hospitals are now resistant to at least one common antibiotic. Mortality rates from infectious diseases are on the rise, by almost 58% just in the course of 12 years. Anticipating a future of untreatable epidemics, the World Health Organization has called for concentrated efforts to address antimicrobial resistance and to develop new antibiotics. Resorting to stronger antibiotics, however, only seems to speed up the evolutionary response in pathogenic bacteria. Novel strategies are needed to address antimicrobial resistance. We will investigate the utility of antimicrobial peptides as a potential new approach.
The ability of human beta-defensins hBD-1, hBD-2 and hBD-3 to exert direct in vitro antimicrobial effects was evaluated using Francisella tularensis Live Vaccine Strain (LVS) and Francisella novicida. While hBD-2 showed some antimicrobial activity in these assays, only hBD-3 demonstrated significant potency against Francisella. Francisella tularensis LVS infection induced elevated levels of hBD-2 mRNA in human airway epithelial (A549) cells, while having no significant impact on the levels of hBD-3 and only a moderate effect on the level of hBD-1 mRNA. Francisella infection avoided stimulating the production of the most potent anti-Francisella host peptide, hBD-3, in A549 cells, although hBD-3 is stimulated by other treatments. The differential induction of beta-defensins in Francisella infected lung epithelial cells suggests a complex dynamic in the expression of antimicrobial peptides and the innate immune response.