M ycoplasma canis infects many mammalian hosts but is usually thought of as a commensal or opportunistic cofactor in respiratory or urogenital tract diseases of dogs (1). We found unexpectedly that M. canis was also detectable by culture or PCR in a majority of brain tissue specimens in a retrospective case-control study of canine granulomatous meningoencephalitis (ME) (GME) and necrotizing ME (NME) (2). The presence of M. canis in brain tissue was associated with both GME and NME (both P Ͻ 0.05, as determined by a 2 test). The clinical signs of this common idiopathic neurological disease of dogs include seizures, proprioceptive deficits, circling, and blindness. Immunosuppressive therapy may be palliative, but the syndrome is progressive and uniformly fatal (3). The extensive search for a presumed viral cause of canine GME and NME has been fruitless (4).In humans, bacterial meningitis and encephalitis are multifactorial lethal infections with often severe sequelae for survivors. New detection methods have shown that the variety of bacteria associated with human ME is much more extensive than usually appreciated (5-9). Additional animal models of bacterial ME are necessary to study this broader spectrum of pathogens (10). Since a possible association between M. canis and canine ME was discovered, our objective has been to help fill the void of basic knowledge about the organism's virulence factors, the host responses that it elicits, and its potential roles in pathogenesis. Our working hypotheses were that M. canis is capable of evoking host cell responses that favor dissemination from mucosal surfaces to secondary sites of infection, possibly in a strain-dependent fashion, and also that, regardless of how it might reach those sites, the presence of M. canis there modulates inflammation and direct injury to host cells. Understanding this potential can be expected to help evaluate the cause of canine ME and other diseases.(Portions of these data were presented in abstract form at Congresses of the International Organization for Mycoplasmology [90,91].)
MATERIALS AND METHODSMycoplasma strains and cultivation. Strain PG14 T of M. canis (ATCC 19525) was first isolated from the throat of a normal dog (11). Strains UF31, UF33, LV, 5, 26, Cal, and Mara were first isolated from vaginal swabs of dogs without ME (12). Strains UFG1, UFG2, UFG3, and UFG4 were isolated from frozen brain tissues from cases of canine NME (2). Mycoplasma cynos strain H-831 T (ATCC 27544) was first isolated from the lung of a dog with pneumonia (13). Mycoplasma arginini strain G230 T , Mycoplasma bovigenitalium strain PG11 T , Mycoplasma edwardii strain PG24 T , Mycoplasma maculosum strain Skotti B, Mycoplasma molare strain H542 T , Mycoplasma opalescens strain MH5408 T , and Mycoplasma spumans strain PG13T , representing other species that have been isolated from dogs (1), were obtained from The Mollicutes Collection. All strains were propagated under standard conditions (14) in ATCC 988 medium supplemented with fetal bovine serum (FBS) and glu...