Intracellular Legionella Pneumophila Research Articles

Bactericidal effects of amoxyciffin/clavulanic acid against a Legionella pneumophila pneumonia in the weanling rat

Amoxycillin/clavulanic acid and clavulanic acid have been previously reported to demonstrate bactericidal activity in tissue culture studies against intracellular Legionella pneumophila. A rat model of legionellosis was therefore developed for the purpose of assessing the efficacy of these agents against L. pneumophila in vivo. Therapy by the subcutaneous route was started 12 h after infection when the majority of the bacteria observed in lavage fluid were residing in alveolar macrophages. Treatment with amoxycillin was ineffective in reducing the bacterial counts of L. pneumophila in lung homogenates whereas amoxycillin/clavulanic acid displayed bactericidal effects of the same order as the control antibiotic, erythromycin. Further in-vivo studies are planned to assess the clinical relevance of these findings.

Genetic control of natural resistance in mouse macrophages regulating intracellular Legionella pneumophila multiplication in vitro

It is known that Legionella pneumophila proliferates in peritoneal macrophage cultures derived from A/J mice but not in macrophage cultures derived from many other strains, including C57BL/6 mice. To analyze the genetic control of this trait and the location of the Legionella resistance-susceptibility gene, we prepared segregating progeny of A/J and C57BL/6 mice and determined the levels of susceptibility of individual mice. Peritoneal macrophages were collected by injecting thioglycolate medium, and macrophage monolayers were infected in vitro with L. pneumophila Philadelphia-1. Counting of colonies on buffered charcoal yeast extract agar plates and Gimenez staining of macrophage monolayers were carried out daily. There was a 10-fold increase in bacterial burden 1 day after infection and a 100-fold increase after 2 days in A/J (susceptible) macrophages. The increase in bacterial burden was always less than 10-fold in macrophages from C57BL/6 (resistant) progenitors, A/J x C57BL/6 F1 hybrids, and C57BL/6 x F1 backcross progeny. The ratios of resistant individuals to susceptible individuals were 22:6 for F2 progeny and 20:22 for A/J x F1 backcross progeny. The fact that the organism did not proliferate in macrophages from B10.A mice demonstrated that major histocompatibility antigens did not regulate the macrophage resistance of C57BL/6-derived mice. The sex and coat color genes of mice were not linked to the resistance-susceptibility gene. We suggest that resistance and susceptibility are controlled by a single gene or closely linked genes which are autosomal and that the resistance allele is dominant. The results of a comparison of the strain distribution pattern of this trait with the distribution pattern of 185 allelic markers in A/J x C57BL/6 and C57BL/6 x A/J recombinant inbred strains suggest that this susceptibility-resistance gene is located in the proximal part of chromosome 15.