Amrita Lama, Samuel L. Drennan, Rudd C. Johnson, Grace L. Rubenstein, Eric D. Cambronne
Abstract
It is established that the human pathogen Legionella pneumophila becomes significantly augmented for infection of macrophages after intracellular growth in amoebae when compared to like-strains cultivated in laboratory media. Based on this observation, we reasoned that the most critical virulence determinants of L.p. are expressed by responding to stimuli generated by the protozoan host specifically; a process we term "protozoan-priming." We sought to identify L.p. virulence factors that were required for replication in amoebae in order to highlight the genes necessary for production of the most infectious form of the bacterium. Using a transposon mutagenesis screen, we successfully identified 12 insertions that produced bacteria severely attenuated for growth in amoebae, while retaining a functional Dot/Icm type IVb secretion system. Seven of these insertion mutants were found dispensable for growth in macrophages, revealing attractive therapeutic targets that reside upstream of the pathogen-human interface. Two candidates identified, lpg0730 and lpg0122 were required for survival and replication in amoebae and macrophage host cells. Both genes are conserved among numerous important human pathogenic bacteria that can persist or replicate in amoebae. Each gene encodes a component of an ATP binding cassette (ABC) transport complex of unknown function. We demonstrate the lpg0730 ortholog in Francisella tularensis subsp. novicida to be essential for colonization of both protozoan and mammalian host cells, highlighting conserved survival mechanisms employed by bacteria that utilize protozoa as an environmental reservoir for replication.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 August 2018.
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#13,574,541
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Outputs from Frontiers in Cellular and Infection Microbiology
#2,258
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#215,782
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Outputs of similar age from Frontiers in Cellular and Infection Microbiology
#48
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Altmetric has tracked 23,009,818 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,499 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one has gotten more attention than average, scoring higher than 62% of its peers.
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We're also able to compare this research output to 111 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
