Abstract
Peptoids (oligo N-substituted glycines) are peptide analogues, which can be designed to mimic host antimicrobial peptides, with the advantage that they are resistant to proteolytic degradation. Few studies on the antimicrobial efficacy of peptoids have focused on Gram negative anaerobic microbes associated with clinical infections, which are commonly recalcitrant to antibiotic treatment. We therefore studied the cytotoxicity and antibiofilm activity of a family of peptoids against the Gram negative obligate anaerobe Fusobacterium nucleatum, which is associated with infections in the oral cavity. Two peptoids, peptoid 4 (NaeNpheNphe)4 and peptoid 9 (NahNspeNspe)3 were shown to be efficacious against F. nucleatum biofilms at a concentration of 1 μM. At this concentration, peptoids 4 and 9 were not cytotoxic to human erythrocytes or primary human gingival fibroblast cells. Peptoids 4 and 9 therefore have merit as future therapeutics for the treatment of oral infections.
Highlights
A plethora of different management strategies exists for the treatment ofGram negative anaerobic infections in the oral cavity, including the administration of systemic antibiotics
Fusobacterium nucelatum is a Gram negative obligate anaerobe that plays an important role in the developing oral plaque biofilm, in the transition from the commensal Gram positive aerobes found in healthy mouths to the pathological Gram negative anaerobes associated with the pathogenesis of infections such as periodontal disease and peri-implantitis in the oral cavity [21]
The family of peptoids studied had previously been examined for their cytotoxicity against HepG2 epithelial and HaCaT keratinocyte cell lines [10], but had not been tested for their cytocoxicity against human erythrocytes or primary cells
Summary
A plethora of different management strategies exists for the treatment ofGram negative anaerobic infections in the oral cavity, including the administration of systemic antibiotics. Short cationic host defence peptides have been investigated as alternatives to antibiotics, having both antimicrobial and immunomodulatory functions [1,2,3]. Viewed as nature’s antibiotics, these peptides generally target bacterial cell membranes [1] rather than the specific metabolic pathways targeted by conventional antibiotics. This mechanism of action has the advantage that bacteria are less likely to develop resistance [1]. The therapeutic translation of peptide treatments has been limited by their cost [4], potential toxicity [1] and their susceptibility to proteolytic degradation [1,5,6]
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