Multidrug resistant pathogens represent one of the greatest threats to human health of the new millennium. ESKAPE
bacterial pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter
baumannii, Pseudomonas aeruginosa and other Enterobacteriaceae species) are the leading group among these socalled
superbugs, which rapidly acquire resistances to several (and sometimes all) available antibiotics and cause a
variety of nosocomial infections (e.g. bacteraemia and wound infections).
Our research has been leading an innovative approach based on bacteriophage-derived enzymes (called capsular
depolymerases) against A. baumannii (see video at ref 1). Previously, we found that some bacteriophages (i.e.
viruses that specifically infect bacteria) acquired the ability to infect different Acinetobacter hosts through acquisition
of different capsular depolymerases (2). These enzymes located at the bacteriophage tails bind and degrade specific
bacterial capsules types (2). Recently, recombinantly expressed capsular depolymerases showed to be active in
several environment conditions, non-nontoxic to mammalian cells and able to make A. baumannii fully susceptible to
host complement effect, namely in i) Galleria mellonella caterpillar, ii) murine and iii) human serum models (3, 4). A
single intraperitoneal injection of depolymerase protect 60% of mice from dead, with significant reduction of proinflammatory
cytokine profile (4). We show that capsular depolymerases fit the new trend of antimicrobials needed,
as they are highly specific, stable and refractory to resistance as they do not kill bacteria per se, instead they remove
bacterial surface polysaccharides, diminishing bacterial virulence and exposing them to the host immune system.
This innovative antimicrobial approach can be applied to other pathogenic bacteria.info:eu-repo/semantics/publishedVersio
