Metal requirements of Legionella pneumophila

Abstract

Serial passage of six strains of Legionella pneumophila and one strain of Pseudomonas aeruginosa in a liquid chemically defined medium deficient in trace metals resulted in the death of five L. pneumophila strains and very limited growth in the remaining strain and the P. aeruginosa strain. Addition of either iron or magnesium restored growth to almost normal levels in ail of the strains when early-passage inocula were used. A low concentration of magnesium stimulated growth with cobalt, copper, iron, manganese, molybdenum, vanadium, or zinc. When a complete defined medium containing trace metals was used, growth was inhibited by adding the chelators ethylenediaminetetraacetic acid, citrate, or 2,2'-bipyridyl. Chelator inhibition was partly or fully relieved with either calcium, cobalt, copper, iron, magnesium, manganese, molybdenum, nickel, vanadium, or zinc. P. aeruginosa differed from L. pneumophila in that it required higher concentrations of each chelator to inhibit growth and that its growth was stimulated by only four metals: calcium, iron, magnesium, and zinc. A trace-metal supplement for L. pneumophila was designed which included all metals stimulating growth in these experiments and which proved to be sufficient for optimal growth of all the strains.

Amoeba host‐Legionella synchronization of amino acid auxotrophy and its role in bacterial adaptation and pathogenic evolution

“…Even though L. pneumophila preferentially utilizes amino acids for carbon and energy, in silico analysis of the L. pneumophila genome sequence revealed that this organism is auxotrophic for the seven amino acids Arg, Cys, Ile, Leu, Met, Thr and Val (Cazalet et al, 2004;Chien et al, 2004). Furthermore, it has been shown that the amino acids Arg, Cys, Ile, Leu, Met, Ser, Thr and Val are essential for growth of L. pneumophila in vitro (Pine et al, 1979;George et al, 1980;Reeves et al, 1981;Ristroph et al, 1981;Tesh and Miller, 1981;Tesh et al, 1983;Molofsky and Swanson, 2004;Wieland et al, 2005;Eylert et al, 2010). The four amino acids, Arg, Cys, Gln and Ser, are needed to support growth in vivo (Wieland et al, 2005).…”

“…Even though L. pneumophila absolutely requires amino acids to power intracellular growth, it is auxotrophic for Arg, Cys, Ile, Leu, Met, Thr and Val (Fig. 3) (Pine et al, 1979;George et al, 1980;Reeves et al, 1981;Ristroph et al, 1981;Tesh and Miller, 1981;Tesh et al, 1983;Molofsky and Swanson, 2004;Wieland et al, 2005;Eylert et al, 2010). Surprisingly, Acanthamoebae, a primary host amoeba of L. pneumophila in the aquatic environment, is auxotrophic for Arg, Ile, Leu, Met and Val (Fig.…”

“…Recent evidence indicates idiosyncrasies in novel microbial strategies to trigger generation of essential nutrients from the host to power bacterial proliferation (Alkhuder et al, 2009;Price et al, 2011;Niu et al, 2012;Winter et al, 2013). Legionella pneumophila, although auxotrophic for several amino acids including cysteine, preferentially metabolizes amino acids as the main sources of energy and carbon to power intracellular replication in amoeba and human cells (Pine et al, 1979;George et al, 1980;Reeves et al, 1981;Ristroph et al, 1981;Tesh and Miller, 1981;Tesh et al, 1983;Molofsky and Swanson, 2004;Wieland et al, 2005;Eylert et al, 2010). This organism has evolved an exquisite mechanism to promote host degradation of proteins to generate a plentiful supply of amino acids to power its intracellular replication in a diverse range of amoebal hosts and the evolutionarily distant human host (Al-Khodor et al, 2008;Price et al, 2009;2010b;2011).…”

IroT/mavN, a new iron‐regulated gene involved in Legionella pneumophila virulence against amoebae and macrophages

“…Legionella pneumophila infects humans via inhalation of contaminated aerosols (Steinert et al, 2002). Iron is a key nutrient for most bacteria in particular for many pathogens (Leong et al, 1974;Weinberg, 1978;Reeves et al, 1981;Ratledge and Dover, 2000;Schaible and Kaufmann, 2004). It is essential as a cofactor in various enzymatic reactions like respiration, oxidative stress response or DNA replication, but can also be a toxic element at elevated intracellular concentrations by catalysing the Fenton reaction.…”

Structure of the GTPase and GDI domains of FeoB, the ferrous iron transporter of Legionella pneumophila

“…Iron is essential for Legionella growth [5] and the pathogen has developed strategies for the efficient uptake of ferric (Fe 3+ ) iron using siderophores such as legiobactin [6]. Ferrous iron (Fe 2+ ) is critical for L. pneumophila growth under low-oxygen conditions in host cells, and in the mammalian lung [7].…”