Human Ribonucleases and Derived peptides to Tackle Antimicrobial Resistance

Emergence of bacterial resistance to most common antibiotics
urges the design of novel antimicrobial drugs. Antimicrobial
proteins andpeptides (AMPPs) are key players of the host innate
immunity and exert a rapid and multifaceted action that reduces
the development of bacterial adaptation mechanisms. Our research
group has been long-time exploring the mechanism of action
of human ribonucleases involved in host defence. Human host
defence RNases is members of the vertebrate specific RNase A
superfamily. They are expressed by a diversity of innate immune
cells and are endowed with antimicrobial properties. Secreted
upon infection, they contribute to protect our body fluids from
invading pathogens. We have identified the structural determinants
that determine the protein antimicrobial activity. A combined
multifaceted action ensures an efficient eradication of bacterial
resistant forms such as biofilm communities and macrophage
intracellular resident mycobacteria. Based on structure- functional
studies and by applying a positional scanning library we have
identified the minimal pharmacophore entity and designed derived
peptides that encompasses most of the parental protein properties.
The results underline the potentiality of RNases and derivatives as
alternative antibiotics to combat bacterial resistance.