A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastase-like serine proteases.
Serpins form a large class of protease inhibitors involved in regulation of a wide spectrum of physiological processes. Recently identified prokaryotic members of this protein family may provide a key to the evolutionary origins of the unique serpin fold and the associated inhibitory mechanism. We performed a biochemical characterization of a serpin from Bifidobacterium longum, an anaerobic Gram-positive bacterium that naturally colonizes human gastrointestinal tract. The B. longum serpin was shown to efficiently inhibit eukaryotic elastase-like proteases with a stoichiometry of inhibition close to 1. Porcine pancreatic elastase and human neutrophil elastase were inhibited with the second order association constants of 4.7 x 10(4) m(-1) s(-1) and 2.1 x 10(4) m(-1) s(-1), respectively. The B. longum serpin is expected to be active in the gastrointestinal tract, because incubation of the purified recombinant serpin with mouse feces produces a stable covalent serpin-protease adduct readily detectable by SDS-PAGE. Bifidobacteria may encounter both pancreatic elastase and neutrophil elastase in their natural habitat and protection against exogenous proteolysis may play an important role in the interaction between these commensal bacteria and their host.
Ivanov
Dmitri
D
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland. Electronic address: dmitri_ivanov@hms.harvard.edu.
Emonet
Celine
C
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
Foata
Francis
F
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
Affolter
Michael
M
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
Delley
Michelle
M
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
Fisseha
Makda
M
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
Blum-Sperisen
Stephanie
S
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
Kochhar
Sunil
S
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
Arigoni
Fabrizio
F
Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland. Electronic address: fabrizio.arigoni@rdls.nestle.com.
D000595:Amino Acid Sequence; D000818:Animals; D001644:Bifidobacterium / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D005243:Feces; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D015843:Serpins / Q000737:chemistry*; D013552:Swine
D015842:Serine Proteinase Inhibitors; D015843:Serpins; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase