INABILITY OF AN ISOGENIC UREASE-NEGATIVE MUTANT STRAIN OF HELICOBACTER-MUSTELAE TO COLONIZE THE FERRET STOMACH

Eight ferrets specific-pathogen-free for Helicobacter mustelae were gi ven, per dose, approximately 3.0 x 10(7) CFU of either the wild-type p arent strain of H. mustelae (NCTC 12032) (two ferrets), the isogenic u rease-negative mutant strain of H. mustelae (10::Tn3Km) (four ferrets) , or sterile culture broth (two ferrets). Infection status was monitor ed by endoscopic gastric biopsy for urease activity, histopatlhology, and culture and by serology at 3, 6, 10, and 21 weeks. All ferrets wer e necropsied at 25 weeks. Both negative control ferrets remained uninf ected, both ferrets receiving the H. mustelae wild-type parent strain became infected after two doses of the organism, and all four ferrets given two doses of the isogenic urease-negative mutant strain of H. mu stelae remained uninfected throughout the 6-month study. Histopatholog y correlated with infection status. H. mustelae-infected ferrets exhib ited diffuse mononuclear inflammation in the subglandular region and t he lamina propria of the gastric mucosa, while uninfected ferrets show ed no or minimal inflammation. These results suggest that urease activ ity is essential for colonization of the ferret stomach by H. mustelae .