Bacterial Ortholog of Mammalian Translocator Protein (TSPO) with Virulence Regulating Activity Export

@article{citeulike:5027795, abstract = {<p>The translocator protein (TSPO), previously designated as peripheral-type benzodiazepine receptor, is a protein mainly located in the outer mitochondrial membrane of eukaryotic cells. TSPO is implicated in major physiological functions and functionally associated with other proteins such as the voltage-dependent anionic channel, also designated as mitochondrial porin. Surprisingly, a TSPO-related protein was identified in the photosynthetic bacterium <italic>Rhodobacter sphaeroides</italic> but it was initially considered as a relict of evolution. In the present study we cloned a <italic>tspO</italic> gene in <italic>Pseudomonas fluorescens</italic> MF37, a non-photosynthetic eubacterium and we used bioinformatics tools to identify TSPO in the genome of 97 other bacteria. <italic>P. fluorescens</italic> TSPO was recognized by antibodies against mouse protein and by PK 11195, an artificial ligand of mitochondrial TSPO. As in eukaryotes, bacterial TSPO appears functionally organized as a dimer and the apparent Kd for PK 11195 is in the same range than for its eukaryotic counterpart. When <italic>P. fluorescens</italic> MF37 was treated with PK 11195 (10⁻⁵ M) adhesion to living or artificial surfaces and biofilm formation activity were increased. Conversely, the apoptotic potential of bacteria on eukaryotic cells was significantly reduced. This effect of PK11195 was abolished in a mutant of <italic>P. fluorescens</italic> MF37 deficient for its major outer membrane porin, OprF. The present results demonstrate the existence of a bacterial TSPO that shares common structural and functional characteristics with its mammalian counterpart. This protein, apparently involved in adhesion and virulence, reveals the existence of a possible new inter kingdom signalling system and suggests that the human microbiome should be involuntarily exposed to the evolutionary pressure of benzodiazepines and related molecules. This discovery also represents a promising opportunity for the development of alternative antibacterial strategies.</p>}, author = {Chapalain, Annelise and Chevalier, Sylvie and Orange, Nicole and Murillo, Laurence and Papadopoulos, Vassilios and Feuilloley, Marc G.}, citeulike-article-id = {5027795}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0006096}, doi = {10.1371/journal.pone.0006096}, journal = {PLoS ONE}, keywords = {bacteria, eukarya, membrane, orthology, protein, pseudomonas, virulence}, month = {June}, number = {6}, pages = {e6096+}, posted-at = {2009-07-01 00:22:53}, priority = {2}, publisher = {Public Library of Science}, title = {Bacterial Ortholog of Mammalian Translocator Protein (TSPO) with Virulence Regulating Activity}, url = {http://dx.doi.org/10.1371/journal.pone.0006096}, volume = {4}, year = {2009} }

TY - JOUR ID - citeulike:5027795 L3 - citeulike-article-id:5027795 N2 - <p>The translocator protein (TSPO), previously designated as peripheral-type benzodiazepine receptor, is a protein mainly located in the outer mitochondrial membrane of eukaryotic cells. TSPO is implicated in major physiological functions and functionally associated with other proteins such as the voltage-dependent anionic channel, also designated as mitochondrial porin. Surprisingly, a TSPO-related protein was identified in the photosynthetic bacterium <italic>Rhodobacter sphaeroides</italic> but it was initially considered as a relict of evolution. In the present study we cloned a <italic>tspO</italic> gene in <italic>Pseudomonas fluorescens</italic> MF37, a non-photosynthetic eubacterium and we used bioinformatics tools to identify TSPO in the genome of 97 other bacteria. <italic>P. fluorescens</italic> TSPO was recognized by antibodies against mouse protein and by PK 11195, an artificial ligand of mitochondrial TSPO. As in eukaryotes, bacterial TSPO appears functionally organized as a dimer and the apparent Kd for PK 11195 is in the same range than for its eukaryotic counterpart. When <italic>P. fluorescens</italic> MF37 was treated with PK 11195 (10⁻⁵ M) adhesion to living or artificial surfaces and biofilm formation activity were increased. Conversely, the apoptotic potential of bacteria on eukaryotic cells was significantly reduced. This effect of PK11195 was abolished in a mutant of <italic>P. fluorescens</italic> MF37 deficient for its major outer membrane porin, OprF. The present results demonstrate the existence of a bacterial TSPO that shares common structural and functional characteristics with its mammalian counterpart. This protein, apparently involved in adhesion and virulence, reveals the existence of a possible new inter kingdom signalling system and suggests that the human microbiome should be involuntarily exposed to the evolutionary pressure of benzodiazepines and related molecules. This discovery also represents a promising opportunity for the development of alternative antibacterial strategies.</p> IS - 6 JF - PLoS ONE TI - Bacterial Ortholog of Mammalian Translocator Protein (TSPO) with Virulence Regulating Activity PB - Public Library of Science VL - 4 SP - e6096 KW - bacteria KW - eukarya KW - membrane KW - orthology KW - protein KW - pseudomonas KW - virulence AU - Chapalain, Annelise AU - Chevalier, Sylvie AU - Orange, Nicole AU - Murillo, Laurence AU - Papadopoulos, Vassilios AU - Feuilloley, Marc PY - 2009/06/30/ UR - http://dx.doi.org/10.1371/journal.pone.0006096 ER -