RT Journal Article SR Electronic T1 Decomposing virulence to understand bacterial clearance in persistent infections JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.29.437521 DO 10.1101/2021.03.29.437521 A1 Beatriz Acuña Hidalgo A1 Luís M. Silva A1 Roland R. Regoes A1 Mathias Franz A1 Sophie A. O. Armitage YR 2021 UL http://biorxiv.org/content/early/2021/03/30/2021.03.29.437521.abstract AB 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 StatementThe authors have declared no competing interest.