Amino acid requirements of Legionella pneumophila

George, J R; Pine, Leo; Reeves, Michael W.; Harrell, William K.

doi:10.1128/jcm.11.3.286-291.1980

Cited by 115 publications

(65 citation statements)

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“…The nature of the energy and carbon sources utilized by intracellular L. pneumophila is only partially known. Based on studies of broth cultures, the bacterium is thought to utilize only amino acids, mainly serine (Pine et al, 1979;George et al, 1980). Indeed, during the RP in amoebae, genes corresponding to many of its amino acid degradation pathways are upregulated (Table S3A).…”

Section: The Diet Of Intracellular L Pneumophila: Robbery Of Host Ammentioning

confidence: 99%

Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila

et al. 2006

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SummaryAdaptation to the host environment and exploitation of host cell functions are critical to the success of intracellular pathogens. Here, insight to these virulence mechanisms was obtained for the first time from the transcriptional program of the human pathogen Legionella pneumophila during infection of its natural host, Acanthamoeba castellanii . The biphasic life cycle of L. pneumophila was reflected by a major shift in gene expression from replicative to transmissive phase, concerning nearly half of the genes predicted in the genome. However, three different L. pneumophila strains showed similar in vivo gene expression patterns, indicating that common regulatory mechanisms govern the Legionella life cycle, despite the plasticity of its genome. During the replicative phase, in addition to components of aerobic metabolism and amino acid catabolism, the Entner-Doudoroff pathway, a NADPH producing mechanism used for sugar and/or gluconate assimilation, was expressed, suggesting for the first time that intracellular L. pneumophila may also scavenge host carbohydrates as nutrients and not only proteins. Identification of genes only upregulated in vivo but not in vitro , may explain higher virulence of in vivo grown L. pneumophila. Late in the life cycle, L. pneumophila upregulates genes predicted to promote transmission and manipulation of a new host cell, therewith priming it for the next attack. These including substrates of the Dot/Icm secretion system, other factors associated previously with invasion and virulence, the motility and the type IV pilus machineries, and > 90 proteins not characterized so far. Analysis of a fliA ( s 28 ) deletion mutant identified genes coregulated with the flagellar regulon, including GGDEF/EAL regulators and factors that promote host cell entry and survival.

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Section: The Diet Of Intracellular L Pneumophila: Robbery Of Host Ammentioning

confidence: 99%

Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila

et al. 2006

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“…Legionella pneumophila relies on amino acids as the main source of energy and carbon, although carbohydrates may be a minor substrate (George et al, 1980;Ristroph et al, 1981;Tesh and Miller, 1981;Eylert et al, 2010). 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).…”

Section: Amino Acid Requirements Of L Pneumophilamentioning

confidence: 99%

“…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).…”

Section: Amino Acid Requirements Of L Pneumophilamentioning

confidence: 99%

“…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.…”

Section: Synchronization Of Amino Acid Auxotrophymentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Price

Richards

Dwingelo

et al. 2013

Environmental Microbiology

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Summary Legionella pneumophila, the causative agent of Legionnaires’ disease, invades and proliferates within a diverse range of free-living amoeba in the environment but upon transmission to humans the bacteria hijack alveolar macrophages. Intracellular proliferation of L. pneumophila in two evolutionarily distant hosts is facilitated by bacterial exploitation of conserved host processes that are targeted by bacterial protein effectors injected into the host cell. A key aspect of microbe-host interaction is microbial extraction of nutrients from the host but understanding of this is still limited. AnkB functions as a nutritional virulence factor and promotes host proteasomal degradation of polyubiquitinated proteins generating gratuitous levels of limiting host cellular amino acids. L. pneumophila is auxotrophic for several amino acids including cysteine, which is a metabolically preferred source of carbon and energy during intracellular proliferation, but is limiting in both amoebae and humans. We propose that synchronization of bacterial amino acids auxotrophy with the host is a driving force in pathogenic evolution and nutritional adaptation of L. pneumophila and other intracellular bacteria to life within the host cell. Understanding microbial strategies of nutrient generation and acquisition in the host will provide novel antimicrobial strategies to disrupt pathogen access to essential sources of carbon and energy.

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The life stage‐specific pathometabolism of Legionella pneumophila

Eisenreich

Heuner

2016

FEBS Letters

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The genus Legionella belongs to Gram-negative bacteria found ubiquitously in aquatic habitats, where it grows in natural biofilms and replicates intracellularly in various protozoa (amoebae, ciliates). L. pneumophila is known as the causative agent of Legionnaires' disease, since it is also able to replicate in human alveolar macrophages, finally leading to inflammation of the lung and pneumonia. To withstand the degradation by its host cells, a Legionellacontaining vacuole (LCV) is established for intracellular replication, and numerous effector proteins are secreted into the host cytosol using a type four B secretion system (T4BSS). During intracellular replication, Legionella has a biphasic developmental cycle that alternates between a replicative and a transmissive form. New knowledge about the host-adapted and life stagedependent metabolism of intracellular L. pneumophila revealed a bipartite metabolic network with life stage-specific usages of amino acids (e.g. serine), carbohydrates (e.g. glucose) and glycerol as major substrates. These metabolic features are associated with the differentiation of the intracellular bacteria, and thus have an important impact on the virulence of L. pneumophila.

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Amino acid requirements of Legionella pneumophila

Cited by 115 publications

References 8 publications

Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila

Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila

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

The life stage‐specific pathometabolism of Legionella pneumophila

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