Influence of iron-limited continuous culture on physiology and virulence of Legionella pneumophila.

A virulent strain of Legionella pneumophila serogroup 1, subgroup Pontiac, was grown in continuous culture at a constant growth rate under iron-replete and iron-limited conditions. Iron limitation was achieved by the removal of ferrous sulfate and hemin from the chemically defined medium. Residual contaminating iron, 0.

Experimental Legionnaires' disease in SCID-Beige mice reconstituted with human leucocytes.

A new small animal model of experimental Legionnaires' disease is described in which the reconstitution of SCID-Beige mice with human peripheral blood leucocytes permits the in-vivo growth of Legionella pneumophila in the lungs of aerosol-challenged mice. Following infection, viable bacterial counts within the lungs of mice increased from 10(5) cfu/lung at the time of inoculation to a maximum of 10(10) cfu/lung by 48 h post-inoculation. Two types of disease were detected in the lungs of infected SCID-Beige mice.

Growth temperature reversibly modulates the virulence of Legionella pneumophila.

In chemostat culture, the virulence of two strains of Legionella pneumophila was shown to be significantly (P < 0.05) reduced when the culture temperature was lowered from 37 to 24 degrees C. This modulation was reversed by returning the temperature to 37 degrees C, which resulted in a statistically significant (P < 0.

A comparison of aerosol and intragastric routes of infection with Listeria spp.

Aerosol infection (AI) of Porton outbred mice with Listeria species, exhibiting varying degrees of virulence, was compared with gastric intubation (GI) on the basis of numbers of deaths, 50% lethal dose (LD50) and pattern of listerial infection. The AI route appeared to be more sensitive, efficient and consistent than GI in that it required 10(5) fewer micro-organisms to obtain infection and death then ensued within 4 days, with GI deaths usually occurring on day 7. All the virulent strains tested caused 100% mortality by AI, while virulent and avirulent strains were indistinguishable by GI.

A comparison of the efficacy of azithromycin and clarithromycin in oral therapy of experimental airborne Legionnaires' disease.

The activities of two new macrolides, azithromycin and clarithromycin, were compared in an aerosol-infected guinea-pig model of legionnaires' disease. The results of this study indicate that a low oral dose of azithromycin (3.6 mg/kg) administered once daily gives 100% survival in Legionella pneumophila-infected animals.

Demonstration of the intracellular production of tissue-destructive protease by Legionella pneumophila multiplying within guinea-pig and human alveolar macrophages.

The major extracellular enzyme of Legionella pneumophila, a metalloprotease, has been proposed as a pathogenic factor in Legionnaires' disease due to its cytotoxic, tissue-destructive, and phagocyte-inhibitory properties. The relevance of these activities depends on the production of the protease during infection, i.e.

Transposon mutagenesis in Legionella pneumophila. II.--Mutants exhibiting impaired intracellular growth within cultured macrophages and reduced virulence in vivo.

Transposon Tn5 mutants of L. pneumophila were isolated and screened for loss of virulence-associated characteristics. Three mutants were found with normal ability to produce putative pathogenicity determinants and to be endocytosed by guinea pig alveolar macrophages in vitro but with a greatly reduced ability to multiply within them.

Airborne infection of laying hens with Salmonella enteritidis phage type 4.

Hens were exposed to small-particle aerosols containing different concentrations of Salmonella enteritidis phage type 4. They developed a systemic infection and some birds were still excreting the organism in the faeces when killed 28 days after infection. S enteritidis was present for a similar period in a wide range of alimentary tract issues and in the ovary and oviduct.

Viability and distribution of bacteria after passage through a circle anaesthetic system.

We have assessed in vitro the viability of eight species of micro-organism suspended as aerosols and passed through a soda-lime absorber rebreathing system. As had been predicted, the soda-lime exerted a potent cidal effect on non-sporing organisms, all of which were rendered non-viable. One percent of the spore bearing organism, Bacillus subtilis, was still viable after 30 min contact.

Efficacy of azithromycin in the treatment of guinea pigs infected with Legionella pneumophila by aerosol.

Azithromycin and erythromycin were compared for efficacy in guinea pigs infected with an aerosol containing Legionella pneumophila. When administered intraperitoneally, azithromycin was very effective in the treatment of experimental Legionnaires' disease. Even at the low dose of 3.

Bacterial infection (Legionella pneumophila) stimulates fever, metabolic rate and brown adipose tissue activity in the guinea pig.

The objective of this study was to assess whether bacterial infection stimulates oxygen consumption and brown adipose tissue (BAT) activity. Guinea pigs infected with Legionella pneumophila showed marked fever and a significant (33%) increase in resting oxygen consumption (VO2), 24h after infection. At this time, food intake and body weight were normal and the in vitro thermogenic activity of BAT taken from infected animals was elevated by 64% above that of control guinea pigs.

Effects of inhaled titanium dioxide dust on the lung and on the course of experimental Legionnaires' disease.

Guinea-pigs were exposed for 14 days to an aerosol of titanium dioxide (TiO2) dust to produce macrophage blockade. Groups of the animals were later infected by aerosol with Legionella pneumophila. Histological and ultrastructural studies showed that TiO2 dust alone was inert and non-fibrogenic and even at 6 weeks induced no pathological lesions in the lungs, apart from accumulation of macrophages in interalveolar septa.

The effect of ofloxacin on the intracellular growth of Legionella pneumophila in guinea pig alveolar phagocytes.

Ofloxacin was evaluated as an antibiotic for possible use in the therapy of Legionnaires' disease in relation to its ability to penetrate alveolar phagocytes and inhibit Legionella pneumophila intracellular replication. A comparison with two other antibiotics used in the treatment of Legionnaires' disease, ciprofloxacin and erythromycin, was also made. Ofloxacin was found to be the most effective antibiotic, eliminating viable L.

Effects of polymorphonuclear leucocyte depletion on the pathogenesis of experimental Legionnaires' disease.

Guinea-pigs were depleted of circulating polymorphonuclear leucocytes (PMN) by administration of anti-polymorph serum. Groups of animals were then infected by aerosols containing different doses of Legionella pneumophila and the effects compared with those in intact infected controls. Elimination of PMN lowered the dose of L.

Experimental infection of monkeys with Leptospira interrogans serovar hardjo.

Grivet monkeys experimentally infected with two different strains of Leptospira interrogans serovar hardjo showed no signs of severe clinical disease. There were no significant macroscopic lesions in any of the tissues examined, but the organisms were demonstrated in various tissues by immunofluorescent technique and were isolated from the blood and urine of two monkeys and the kidney of one. Abraded skin was shown to be a viable route of infection in non-human primates.

The effect of oxygen-dependent antimicrobial systems on strains of Legionella pneumophila of different virulence.

Four strains of Legionella pneumophila of different virulence as identified by ability to produce pneumonia and death in guinea-pigs infected by a fine-particle aerosol were examined for factors which may intracellularly influence virulence. Possible bactericidal mechanisms possessed by alveolar phagocytes were examined. A relationship could be established between resistance to H2O2, catalase activity and virulence amongst the strains.

A comparison of virulence of two strains of Legionella pneumophila based on experimental aerosol infection of guinea-pigs.

Two strains of Legionella pneumophila (LP) serogroup I, of differing virulence, were examined in terms of numbers of viable organisms in tissues, pyrexia and mortality following aerosol infection. The Corby strain was the more virulent, with pyrexia and deaths of guinea-pigs 3 to 6 days after infection. This strain multiplied very rapidly in the lungs to reach a peak of 5 X 10(11) viable organisms/lung.

Non-specific protection against pulmonary Legionella pneumophila infection in guinea-pigs immunized and challenged with mycobacteria.

Experiments were designed to test the ability of the non-specific efferent limb of cell mediated immunity (CMI) to protect guinea-pigs against a lethal L. pneumophila challenge. A secondary CMI response was generated in the lungs of guinea-pigs using an established protocol which consisted of intraperitoneal infection with Mycobacterium bovis BCG followed by intravenous infection with Mycobacterium tuberculosis H37Ra.

Studies on ciprofloxacin therapy of experimental Legionnaires' disease.

The concentration of ciprofloxacin in the serum and tissues of normal guinea-pigs was monitored after intramuscular and oral administration. Significant concentrations were attained in the kidneys, but higher doses were required before serum and lung concentrations became measurable. Ciprofloxacin, given parenterally, prevented pyrexia and death of guinea-pigs infected by aerosols of Legionella pneumophila.