A Tick Antivirulence Protein Potentiates Antibiotics against Staphylococcus aureus

Abstract

New strategies are needed to combat antibiotic resistance, especially against pathogens such as methicillin-resistant <i>Staphylococcus aureus</i> A tick antifreeze glycoprotein, IAFGP, possesses potent antibiofilm properties against a variety of clinical pathogens, including <i>S. aureus</i> Synergy between IAFGP, or a peptide (P1) representative of a repeat region of the protein, with different antibiotics was assessed <i>in vitro</i> Antibiotics that synergized with either IAFPG or P1 were further evaluated <i>in vivo</i> using vertebrate and invertebrate infection models. IAFGP readily enhanced the efficacy of antibiotics against <i>S. aureus</i> Synergy with daptomycin, an antibiotic used to treat methicillin-resistant <i>S. aureus</i>, was observed <i>in vitro</i> and <i>in vivo</i> using <i>iafgp</i>-transgenic mice and flies. Furthermore, synergy with ciprofloxacin or gentamicin, antibiotics not generally used to treat <i>S. aureus</i>, was also perceived. The combined effect of the antibiotic and IAFGP was associated with improved permeation of the antibiotic into the cell. Our results highlight that synergy of IAFGP with antibiotics traditionally used to treat this pathogen, and enhancement of the potency of antibiotics not commonly used against this microbe, can provide novel alternative therapeutic strategies to combat bacterial infections.