The protective efficacies of bacille Calmette-Guérin (BCG) and Mycobacterium avium-intracellulare (MAI) were examined in guinea pigs that were infected by the respiratory route with one of three strains of Mycobacterium tuberculosis: two strains obtained as recent sputum isolates from an ongoing BCG trial in south India and laboratory strain H37Rv. Groups of animals were given all combinations of two treatments with BCG, MAI, or placebo and than challenged. The numbers of tubercle bacilli recovered from the primary lung lesions, primary lesion-free lung lobes, and spleens were used to estimate the relative protective effects of the various treatments. In general, BCG and MAI protected equally well against the low-virulence strain of M. tuberculosis. For the two more virulent strains the results were less clear; however, a substantial protective effect of MAI compared with BCG was noted. Infection with MAI did not significantly alter the capacity of BCG to protect against tuberculous infection.
SummaryHarmful and beneficial bacterium-host interactions induce similar host-tissue changes that lead to contrasting outcomes of association. A life-long association between Vibrio fischeri and the light organ of its host Euprymna scolopes begins when the squid collects bacteria from the surrounding seawater using mucus secreted from ciliated epithelial appendages. Following colonization, the bacterium causes changes in host tissue including cessation of mucus shedding, and apoptosis and regression of the appendages that may limit additional bacterial interactions. We evaluated whether delivery of morphogenic signals is influenced by GacA, a virulence regulator in pathogens, which also influences squidcolonization by V. fischeri. Low-level colonization by a GacA mutant led to regression of the ciliated appendages. However, the GacA mutant did not induce cessation of mucus shedding, nor did it trigger apoptosis in the appendages, a phenotype that normally correlates with their regression. Because apoptosis is triggered by lipopolysaccharide, we examined the GacA mutant and determined that it had an altered lipopolysaccharide profile as well as an increased sensitivity to detergents. GacAmutant-colonized animals were highly susceptible to invasion by secondary colonizers, suggesting that the GacA mutant's inability to signal the full programme of light-organ responses permitted the prolonged recruitment of additional symbionts.
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