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Comparative analyses of Legionella species identifies genetic features of strains causing Legionnaires' disease.

Gomez-Valero L, Rusniok C, Rolando M, Neou M, Dervins-Ravault D, Demirtas J, Rouy Z, Moore RJ, Chen H, Petty NK, Jarraud S, Etienne J, Steinert M, Heuner K, Gribaldo S, Médigue C, Glöckner G, Hartland EL, Buchrieser C - Genome Biol. (2014)

Bottom Line: To identify the genetic bases underlying the different capacities to cause disease we sequenced and compared the genomes of L. micdadei, L. hackeliae and L. fallonii (LLAP10), which are all rarely isolated from humans.The Dot/Icm secretion system is conserved, although the core set of substrates is small, as only 24 out of over 300 described Dot/Icm effector genes are present in all Legionella species.Key factors such as proteins involved in oxygen binding, iron storage, host membrane transport and certain Dot/Icm substrates are specific features of disease-related strains.

View Article: PubMed Central - PubMed

ABSTRACT

Background: The genus Legionella comprises over 60 species. However, L. pneumophila and L. longbeachae alone cause over 95% of Legionnaires’ disease. To identify the genetic bases underlying the different capacities to cause disease we sequenced and compared the genomes of L. micdadei, L. hackeliae and L. fallonii (LLAP10), which are all rarely isolated from humans.

Results: We show that these Legionella species possess different virulence capacities in amoeba and macrophages, correlating with their occurrence in humans. Our comparative analysis of 11 Legionella genomes belonging to five species reveals highly heterogeneous genome content with over 60% representing species-specific genes; these comprise a complete prophage in L. micdadei, the first ever identified in a Legionella genome. Mobile elements are abundant in Legionella genomes; many encode type IV secretion systems for conjugative transfer, pointing to their importance for adaptation of the genus. The Dot/Icm secretion system is conserved, although the core set of substrates is small, as only 24 out of over 300 described Dot/Icm effector genes are present in all Legionella species. We also identified new eukaryotic motifs including thaumatin, synaptobrevin or clathrin/coatomer adaptine like domains.

Conclusions: Legionella genomes are highly dynamic due to a large mobilome mainly comprising type IV secretion systems, while a minority of core substrates is shared among the diverse species. Eukaryotic like proteins and motifs remain a hallmark of the genus Legionella. Key factors such as proteins involved in oxygen binding, iron storage, host membrane transport and certain Dot/Icm substrates are specific features of disease-related strains.

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Phylogenetic analysis shows the eukaryotic origin of the carboxypeptidase S28 family protein (Llo0042/Lfa0022). The species belonging to bacteria and eukaryotes are shown in red and green, respectively. Numbers next to tree nodes correspond to bootstrap values. The bar at the bottom represents the estimated evolutionary distance.
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Fig7: Phylogenetic analysis shows the eukaryotic origin of the carboxypeptidase S28 family protein (Llo0042/Lfa0022). The species belonging to bacteria and eukaryotes are shown in red and green, respectively. Numbers next to tree nodes correspond to bootstrap values. The bar at the bottom represents the estimated evolutionary distance.

Mentions: Among these proteins 27 had not been described before and 15 were identified in the newly sequenced species. A clear case of horizontal gene transfer from eukaryotes is GamA (Lpp0489), a glucoamylase that allows Legionella to degrade glycogen during intracellular replication in A. castellanii [66]. In addition to already characterized proteins, we identified promising candidates for host-pathogen interactions in this study - for example, a L. longbeachae protein containing a tubulin-tyrosine ligase domain (Llo2200; Figure S9A in Additional file 14), a motif involved in addition of a carboxy-terminal tyrosine to α-tubulin as part of a tyrosination-detyrosination cycle that is present in most eukaryotic cells. This tyrosination process regulates the recruitment of microtubule-interacting proteins [67]. It is thus tempting to assume that Legionella is able to interfere with or to modulate the recruitment of microtubule-interacting proteins in the host. Another example is the serine carboxypeptidase S28 family protein (Llo0042/Lfa0022; Figure 7). These proteins have been identified exclusively in eukaryotes and are active at low pH, suggesting a function in the phagosome [68].Figure 7


Comparative analyses of Legionella species identifies genetic features of strains causing Legionnaires' disease.

Gomez-Valero L, Rusniok C, Rolando M, Neou M, Dervins-Ravault D, Demirtas J, Rouy Z, Moore RJ, Chen H, Petty NK, Jarraud S, Etienne J, Steinert M, Heuner K, Gribaldo S, Médigue C, Glöckner G, Hartland EL, Buchrieser C - Genome Biol. (2014)

Phylogenetic analysis shows the eukaryotic origin of the carboxypeptidase S28 family protein (Llo0042/Lfa0022). The species belonging to bacteria and eukaryotes are shown in red and green, respectively. Numbers next to tree nodes correspond to bootstrap values. The bar at the bottom represents the estimated evolutionary distance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4256840&req=5

Fig7: Phylogenetic analysis shows the eukaryotic origin of the carboxypeptidase S28 family protein (Llo0042/Lfa0022). The species belonging to bacteria and eukaryotes are shown in red and green, respectively. Numbers next to tree nodes correspond to bootstrap values. The bar at the bottom represents the estimated evolutionary distance.
Mentions: Among these proteins 27 had not been described before and 15 were identified in the newly sequenced species. A clear case of horizontal gene transfer from eukaryotes is GamA (Lpp0489), a glucoamylase that allows Legionella to degrade glycogen during intracellular replication in A. castellanii [66]. In addition to already characterized proteins, we identified promising candidates for host-pathogen interactions in this study - for example, a L. longbeachae protein containing a tubulin-tyrosine ligase domain (Llo2200; Figure S9A in Additional file 14), a motif involved in addition of a carboxy-terminal tyrosine to α-tubulin as part of a tyrosination-detyrosination cycle that is present in most eukaryotic cells. This tyrosination process regulates the recruitment of microtubule-interacting proteins [67]. It is thus tempting to assume that Legionella is able to interfere with or to modulate the recruitment of microtubule-interacting proteins in the host. Another example is the serine carboxypeptidase S28 family protein (Llo0042/Lfa0022; Figure 7). These proteins have been identified exclusively in eukaryotes and are active at low pH, suggesting a function in the phagosome [68].Figure 7

Bottom Line: To identify the genetic bases underlying the different capacities to cause disease we sequenced and compared the genomes of L. micdadei, L. hackeliae and L. fallonii (LLAP10), which are all rarely isolated from humans.The Dot/Icm secretion system is conserved, although the core set of substrates is small, as only 24 out of over 300 described Dot/Icm effector genes are present in all Legionella species.Key factors such as proteins involved in oxygen binding, iron storage, host membrane transport and certain Dot/Icm substrates are specific features of disease-related strains.

View Article: PubMed Central - PubMed

ABSTRACT

Background: The genus Legionella comprises over 60 species. However, L. pneumophila and L. longbeachae alone cause over 95% of Legionnaires’ disease. To identify the genetic bases underlying the different capacities to cause disease we sequenced and compared the genomes of L. micdadei, L. hackeliae and L. fallonii (LLAP10), which are all rarely isolated from humans.

Results: We show that these Legionella species possess different virulence capacities in amoeba and macrophages, correlating with their occurrence in humans. Our comparative analysis of 11 Legionella genomes belonging to five species reveals highly heterogeneous genome content with over 60% representing species-specific genes; these comprise a complete prophage in L. micdadei, the first ever identified in a Legionella genome. Mobile elements are abundant in Legionella genomes; many encode type IV secretion systems for conjugative transfer, pointing to their importance for adaptation of the genus. The Dot/Icm secretion system is conserved, although the core set of substrates is small, as only 24 out of over 300 described Dot/Icm effector genes are present in all Legionella species. We also identified new eukaryotic motifs including thaumatin, synaptobrevin or clathrin/coatomer adaptine like domains.

Conclusions: Legionella genomes are highly dynamic due to a large mobilome mainly comprising type IV secretion systems, while a minority of core substrates is shared among the diverse species. Eukaryotic like proteins and motifs remain a hallmark of the genus Legionella. Key factors such as proteins involved in oxygen binding, iron storage, host membrane transport and certain Dot/Icm substrates are specific features of disease-related strains.

Show MeSH
Related in: MedlinePlus