Antivirulence properties of an antifreeze protein.
As microbial drug-resistance increases, there is a critical need for new classes of compounds to combat infectious diseases. The Ixodes scapularis tick antifreeze glycoprotein, IAFGP, functions as an antivirulence agent against diverse bacteria, including methicillin-resistant Staphylococcus aureus. Recombinant IAFGP and a peptide, P1, derived from this protein bind to microbes and alter biofilm formation. Transgenic iafgp-expressing flies and mice challenged with bacteria, as well as wild-type animals administered P1, were resistant to infection, septic shock, or biofilm development on implanted catheter tubing. These data show that an antifreeze protein facilitates host control of bacterial infections and suggest therapeutic strategies for countering pathogens.
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: martin.heisig@yale.edu.
Martin
M
Heisig
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Nabil M
NM
Abraham
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Lei
L
Liu
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Girish
G
Neelakanta
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Sarah
S
Mattessich
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Hameeda
H
Sultana
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Zhengling
Z
Shang
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Juliana M
JM
Ansari
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Charlotte
C
Killiam
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Wendy
W
Walker
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Lynn
L
Cooley
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Richard A
RA
Flavell
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520, USA.
Herve
H
Agaisse
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: erol.fikrig@yale.edu.
Erol
E
Fikrig
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D021301:Antifreeze Proteins / Q000235:genetics / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D060467:Disease Resistance / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000382:microbiology; D019476:Insect Proteins / Q000235:genetics / Q000494:pharmacology*; D018884:Ixodes / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology
D000900:Anti-Bacterial Agents; D021301:Antifreeze Proteins; D019476:Insect Proteins; D011994:Recombinant Proteins