MIB-MIP is a mycoplasma system that captures and cleaves immunoglobulin G.
Mycoplasmas are "minimal" bacteria able to infect humans, wildlife, and a large number of economically important livestock species. Mycoplasma infections include a spectrum of clinical manifestations ranging from simple fever to fulminant inflammatory diseases with high mortality rates. These infections are mostly chronic, suggesting that mycoplasmas have developed means to evade the host immune response. Here we present and functionally characterize a two-protein system from Mycoplasma mycoides subspecies capri that is involved in the capture and cleavage of IgG. The first component, Mycoplasma Ig binding protein (MIB), is an 83-kDa protein that is able to tightly bind to the Fv region of a wide range of IgG. The second component, Mycoplasma Ig protease (MIP), is a 97-kDa serine protease that is able to cleave off the VH domain of IgG. We demonstrate that MIB is necessary for the proteolytic activity of MIP. Cleavage of IgG requires a sequential interaction of the different partners of the system: first MIB captures the IgG, and then MIP is recruited to the MIB-IgG complex, enabling protease activity. MIB and MIP are encoded by two genes organized in tandem, with homologs found in the majority of pathogenic mycoplasmas and often in multiple copies. Phylogenetic studies suggest that genes encoding the MIB-MIP system are specific to mycoplasmas and have been disseminated by horizontal gene transfer. These results highlight an original and complex system targeting the host immunoglobulins, playing a potentially key role in the immunity evasion by mycoplasmas.
INRA (Institut National de la Recherche Agronomique), UMR 1332 Biologie du Fruit et Pathologie, F-33882 Villenave d'Ornon, France; University of Bordeaux, UMR 1332 Biologie du Fruit et Pathologie, F-33882 Villenave d'Ornon, France; yonathan.arfi@u-bordeaux.fr.
Yonathan
Y
Arfi
Institut Européen de Chimie et Biologie, UMS 3033, University of Bordeaux, 33607 Pessac, France; Institut Bergonié, SIRIC BRIO, 33076 Bordeaux, France;
Laetitia
L
Minder
INSERM U1212, ARN Regulation Naturelle et Artificielle, 33607 Pessac, France; CNRS UMR 5320, ARN Regulation Naturelle et Artificielle, 33607 Pessac, France; Institut Européen de Chimie et Biologie, University of Bordeaux, 33607 Pessac, France;
Carmelo
C
Di Primo
Institut de Biologie Structurale, University of Grenoble Alpes, F-38044 Grenoble, France; CNRS, Institut de Biologie Structurale, F-38044 Grenoble, France; CEA, Institut de Biologie Structurale, F-38044 Grenoble, France;
Aline
A
Le Roy
Institut de Biologie Structurale, University of Grenoble Alpes, F-38044 Grenoble, France; CNRS, Institut de Biologie Structurale, F-38044 Grenoble, France; CEA, Institut de Biologie Structurale, F-38044 Grenoble, France;
Christine
C
Ebel
CNRS UMR 6270, Plateforme PISSARO, Institute for Research and Innovation in Biomedicine - Normandie Rouen, Normandie Université, F-76821 Mont-Saint-Aignan, France;
Laurent
L
Coquet
Proteome Platform, Functional Genomic Center of Bordeaux, University of Bordeaux, F-33076 Bordeaux Cedex, France;
Stephane
S
Claverol
J. Craig Venter Institute, Rockville, MD 20850;
Sanjay
S
Vashee
International Livestock Research Institute, 00100 Nairobi, Kenya; Institute of Veterinary Bacteriology, University of Bern, CH-3001 Bern, Switzerland.
Joerg
J
Jores
INRA (Institut National de la Recherche Agronomique), UMR 1332 Biologie du Fruit et Pathologie, F-33882 Villenave d'Ornon, France; University of Bordeaux, UMR 1332 Biologie du Fruit et Pathologie, F-33882 Villenave d'Ornon, France;
Alain
A
Blanchard
INRA (Institut National de la Recherche Agronomique), UMR 1332 Biologie du Fruit et Pathologie, F-33882 Villenave d'Ornon, France; University of Bordeaux, UMR 1332 Biologie du Fruit et Pathologie, F-33882 Villenave d'Ornon, France;
Pascal
P
Sirand-Pugnet
D001426:Bacterial Proteins / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009176:Mycoplasma mycoides / Q000378:metabolism*; D011485:Protein Binding
D001426:Bacterial Proteins; D007074:Immunoglobulin G; D046912:Multiprotein Complexes
immunoglobulin; mycoplasmas; protease