realized in has disposition at some time agent_in_compromised_process Brucella intracellular replication in macrophage artificially mutated Brucella macrophage - Brucella interaction attenuated disposition mouse - Brucella interaction Brucella intracellular survival B. abortus virb4 mutant MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6541:Watarai et al., 2002]. intracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518). The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898). Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6542:Kim et al., 2005]. The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. See PMID:11988518, 15869716, 15135535