No abstract

Helicobacter hepaticus causes hepatitis in selected strains of mice and in A/JCr mice is linked to liver cancer. To analyze whether H. hepaticus persists in specified ecological niches, to determine whether biomarkers of infection exist, and to analyze the influence of H. hepaticus on hepatocyte proliferation, a longitudinal study of H. hepaticus-infected A/JCr mice was undertaken. A/JCr mice were serially euthanatized from 3 through 18 months and surveyed by enzyme-linked immunosorbent assay; bacterial culture of liver, colon, and cecum; histology; electron microscopy; hepatocyte proliferation indices determined by using 5-bromo-2-deoxyuridine; and measurement of the liver enzyme alanine aminotransferase. In infected animals throughout the 18-month study, H. hepaticus was consistently isolated from the lower bowel but only sporadically from the liver. By electron microscopy, H. hepaticus was noted infrequently and only in bile canaliculi. Infected mice, particularly males, showed chronic inflammation; oval cell, Kupffer cell, and Ito cell hyperplasia; hepatocytomegaly; and bile duct proliferation. The inflammatory and necrotizing lesion was progressive and involved the hepatic parenchyma, portal triads, and intralobular venules. Hepatic adenomas were noted only in male mice, whereas 5-bromo-2-deoxyuridine proliferation indices were markedly increased in both sexes, but especially in males, compared with control A/J mice. Infected mice also developed sustained anti-H. hepaticus serum immunoglobulin G antibody responses and elevated alanine aminotransferase levels. H. hepaticus, which persists in the lower bowels and livers of A/JCr mice, is associated with a chronic proliferative hepatitis, and hepatomas in selected male mice indicate that this novel bacterium may cause an increased risk of hepatic cancer induction in susceptible strains of mice. This murine model should prove useful in dissecting the molecular events operable in the development of neoplasms induced by bacteria belonging to this expanding genera of pathogenic Helicobacter species.

The gene encoding the general stress transcription factor ςB in the gram-positive bacterium Listeria monocytogenes was isolated with degenerate PCR primers followed by inverse PCR amplification. Evidence for gene identification includes the following: (i) phylogenetic analyses of reported amino acid sequences for ςB and the closely related ςFproteins grouped L. monocytogenes ςB in the same cluster with the ςB proteins from Bacillus subtilis and Staphylococcus aureus, (ii) the gene order in the 2,668-bp portion of the L. monocytogenes sigBoperon is rsbU-rsbV-rsbW-sigB-rsbX and is therefore identical to the order of the last five genes of the B. subtilis sigB operon, and (iii) an L. monocytogenesςB mutant had reduced resistance to acid stress in comparison with its isogenic parent strain. The sigB mutant was further characterized in mouse models of listeriosis by determining recovery rates of the wild-type and mutant strains from livers and spleens following intragastric or intraperitoneal infection. Our results suggest that ςB-directed genes do not appear to be essential for the spread of L. monocytogenes to mouse liver or spleen at 2 and 4 days following intragastric or intraperitoneal infection.