Nutrient availability modulating physiology and pathogenicity of Legionella pneumophila

James, Brian William (1997). Nutrient availability modulating physiology and pathogenicity of Legionella pneumophila. PhD thesis The Open University.



A virulent strain of Legionella pneumophila serogroup 1 was established in continuous culture under defined iron-replete conditions at pH 6.9. Iron-limitation and extremes of pH (6.0 and 7.8) influenced the growth and metabolism of L. pneumophila, as manifested by increased metabolic activity, impaired energy coupling, and altered metabolic fluxes. In particular, the physiological versatility of L. pneumophila was demonstrated by a significant decrease in the iron content of biomass (6-fold increase in Yiron), coupled with reduced metabolic efficiency (Ycarbon), in response to iron-limited growth. Iron limitation promoted the accumulation of significant intracellular reserves of poly- ß-hydroxybutyrate (16 % cell dry wt.), which supported long-term survival of L. pneumophila under starvation conditions.

Expression of the important pathogenicity factor, the zinc metalloprotease, was regulated by iron availability. Common iron acquisition mechanisms, such as siderophores and transferrin receptors, were not elaborated by iron-limited cells. However, human transferrin was identified as a potential iron source for L. pneumophila, with the zinc metalloprotease mediating transferrin digestion and possibly iron acquisition. Iron-limitation and extremes of pH also influenced cellular morphology and the surface properties of L. pneumophila, promoting the formation of uniform cultures of short rod-shaped bacteria, with altered fatty acid, phospholipid and protein composition.

In addition to morphological and physiological adaptation, iron limitation had a significant effect on the virulence of L. pneumophila. Iron-replete cells grown at pH 6.9 and 6.0 were highly virulent in a guinea pig model. However, the virulence of L. pneumophila was significantly attenuated (P < 0.05) in response to iron-limited growth. This phenomenon was reversible, and correlated with reduced phagocytosis and / or reduced intracellular survival following infection. Decreasing the pH of iron-limited cultures to 6.0 did not stimulate recovery of culture virulence. Therefore, this study clearly demonstrates that environmental stresses, including iron limitation and extremes of pH, play an important role in modulating the physiology and virulence of L. pneumophila, inducing the expression of distinct phenotypes differing in their ability to persist in nature and cause infection.

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