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Decomposing virulence to understand bacterial clearance in persistent infections

Beatriz Acuña Hidalgo, View ORCID ProfileLuís M. Silva, View ORCID ProfileRoland R. Regoes, View ORCID ProfileMathias Franz, View ORCID ProfileSophie A. O. Armitage
doi: https://doi.org/10.1101/2021.03.29.437521
Beatriz Acuña Hidalgo
1Institute of Biology, Freie Universität Berlin, Königin-Luise-Str. 1-3, 14195 Berlin, Germany
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Luís M. Silva
1Institute of Biology, Freie Universität Berlin, Königin-Luise-Str. 1-3, 14195 Berlin, Germany
2Institute of Biology, University of Neuchâtel, Rue Emilie-Argand 11, 2000 Neuchâtel, Switzerland
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Roland R. Regoes
3Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland
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Mathias Franz
1Institute of Biology, Freie Universität Berlin, Königin-Luise-Str. 1-3, 14195 Berlin, Germany
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Sophie A. O. Armitage
1Institute of Biology, Freie Universität Berlin, Königin-Luise-Str. 1-3, 14195 Berlin, Germany
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  • For correspondence: sophie.armitage@fu-berlin.de
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Abstract

Hosts are not always successful at controlling and eliminating a pathogen. Insects can sustain persistent bacterial infections, but the conditions under which clearance occurs are not well understood. Here we asked what role pathogen virulence and infection dose play in bacterial persistence and clearance in both live and dead flies. We also sought to understand the basis of variation in virulence, by asking if it is due to differences in exploitation, i.e., how well bacteria can replicate inside the host, or due to differences in the amount of damage per parasite inflicted on the host, i.e., per parasite pathogenicity (PPP), and how exploitation and PPP relate to clearance probability. We injected Drosophila melanogaster with one of four bacterial species, which we hypothesised should cover a spectrum of virulence: Enterobacter cloacae, Providencia burhodogranariea, Lactococcus lactis and Pseudomonas entomophila. The injection doses spanned four orders of magnitude, and survival was followed to estimate virulence. Bacterial load was quantified in live flies during the acute (1-4 days) and chronic (7-35 days) phases of infection, and we assayed infection status of flies that had died up to ten weeks post infection. We show that sustained persistent infection and clearance are both possible outcomes for bacterial species across a range of virulence. Bacteria of all species could persist inside the host for at least 75 days, and injection dose partly predicts within species variation in clearance. Our decomposition of virulence showed that species differences in bacterial virulence could be explained by a combination of variation in both exploitation and PPP, and that higher exploitation leads to lower bacterial clearance. These results indicate that bacterial infections in insects persist for considerably longer than previously thought, and that decomposing virulence into exploitation and PPP will help us to understand more about the factors affecting infection clearance.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 30, 2021.
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Decomposing virulence to understand bacterial clearance in persistent infections
Beatriz Acuña Hidalgo, Luís M. Silva, Roland R. Regoes, Mathias Franz, Sophie A. O. Armitage
bioRxiv 2021.03.29.437521; doi: https://doi.org/10.1101/2021.03.29.437521
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Decomposing virulence to understand bacterial clearance in persistent infections
Beatriz Acuña Hidalgo, Luís M. Silva, Roland R. Regoes, Mathias Franz, Sophie A. O. Armitage
bioRxiv 2021.03.29.437521; doi: https://doi.org/10.1101/2021.03.29.437521

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