Following an infection, hosts cannot always clear the pathogen, instead either dying or surviving with a persistent infection. Such variation is ecologically and evolutionarily important because it can affect infection prevalence and transmission, and virulence evolution. However, the factors causing variation in infection outcomes, and the relationship between clearance and virulence are not well understood. Here we show that sustained persistent infection and clearance are both possible outcomes across bacterial species showing a range of virulence in Drosophila melanogaster. Variation in virulence arises because of differences in the two components of virulence: bacterial infection intensity inside the host (exploitation), and the amount of damage caused per bacterium (per parasite pathogenicity). As early-phase exploitation increased, clearance rates later in the infection decreased, whereas there was no apparent effect of per parasite pathogenicity on clearance rates. Variation in infection outcomes is thereby determined by how virulence – and its components – relate to the rate of pathogen clearance. Taken together we demonstrate that the virulence decomposition framework is broadly applicable and can provide valuable insights into host-pathogen interactions.

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.

ATP-diphosphohydrolases (EC 3.6.1.5), also known as ATPDases, NTPases, NTPDases, EATPases or apyrases, are enzymes that hydrolyze a variety of nucleoside tri- and diphosphates to their respective nucleosides, being their activities dependent on the presence of divalent cations, such as calcium and magnesium. Recently, ATP-diphosphohydrolases were identified on the surface of several parasites, such as Trypanosoma sp, Leishmania sp and Schistosoma sp. In parasites, the activity of ATPdiphosphohydrolases has been associated with the purine recuperation and/or as a protective mechanism against the host organism under conditions that involve ATP or ADP, such as immune responses and platelet activation. These proteins have been suggested as possible targets for the development of new antiparasitic drugs. In this review, we will comprehensively address the main aspects of the location and function of ATP-diphosphohydrolase in parasites. Also, we performed a detailed research in scientific database of recent developments in new natural and synthetic inhibitors of the ATPdiphosphohydrolases in parasites.