Multiple differences in pathogen-host cell interactions following a bacterial host shift

Abstract

Novel disease emergence is often associated with changes in pathogen traits that enable pathogen colonisation, persistence and transmission in the novel host environment. While understanding the mechanisms underlying disease emergence is likely to have critical implications for preventing infectious outbreaks, such knowledge is often based on studies of viral pathogens, despite the fact that bacterial pathogens may exhibit very different life histories. Here, we investigate the ability of epizootic outbreak strains of the bacterial pathogen, Mycoplasma gallisepticum, which jumped from poultry into North American house finches (Haemorhous mexicanus), to interact with model avian cells. We found that house finch epizootic outbreak strains of M. gallisepticum displayed a greater ability to adhere to, invade, persist within and exit from cultured chicken embryonic fibroblasts, than the reference virulent (R_low) and attenuated (R_high) poultry strains. Furthermore, unlike the poultry strains, the house finch epizootic outbreak strain HF_1994 displayed a striking lack of cytotoxicity, even exerting a cytoprotective effect on avian cells. Our results suggest that, at epizootic outbreak in house finches, M. gallisepticum was particularly adept at using the intra-cellular environment, which may have facilitated colonisation, dissemination and immune evasion within the novel finch host. Whether this high-invasion phenotype is similarly displayed in interactions with house finch cells, and whether it contributed to the success of the host shift, remains to be determined.Stop Solution provided with the kit. Absorbance readings were made at 490 nm (Molecular Devices SpectraMax). Background was subtracted from the experimental samples using the control medium containing M. gallisepticum sample values. Percentage cytotoxicity was calculated as follows: % cytotoxicity = (Infected cells − Untreated cells)/(Total Maximum LDH − Untreated cells) × 100. Statistical analysis.All statistical analyses were conducted in R 75 . We tested for differences in the ability of the M. gallisepticum strains HF_1994, R_low and R_high to: associate with, invade, adhere to and exit DF-1 cells by running one way ANOVA with percentage cell association, invasion, adherence or avian cell exit (as appropriate) as the response variable and M. gallisepticum isolate (i.e. HF_1994, R_low or R_high) as the explanatory term. Post hoc comparisons were carried out using the Tukey HSD test. Differences in cytotoxicity were modelled using a one-way ANOVA, with percent cytotoxicity (relative to untreated cells) as the response variable, and with cell treatment (i.e. infection with HF_1994, R_low, R_high or untreated control) as the explanatory term. All figures were made using ggplot2 76 .

Levels of pathogen virulence and host resistance both shape the antibody response to an emerging bacterial disease

“…Antibodies are thought to have limited protective benefits against intracellular pathogens, with infections by such pathogens thought to be better controlled through cell-mediated immune responses 34 . In accordance, M. gallisepticum has been shown capable of invading avian cells and persisting in the intracellular environment 35 , and the jump from poultry into house finches was associated with an increased ability to do both 36 . Third, M. gallisepticum may be able to prevent antibody binding.…”

Evolution of the CRISPR-Cas9 defence system inMycoplasma gallisepticumfollowing colonization of a novel bird host

“…One major selective event faced by M. gallisepticum after the jump into house finches was the evolution of host resistance to infection (50–52). The jump gave rise to an epidemic that spread quickly and is thought to have killed millions (13,53), with high mortality rates arising because, in house finches, M. gallisepticum colonises the mucosal surfaces of the conjunctiva and upper respiratory tract, causing a severe conjunctivitis that can lead to death in the wild through blindness-induced starvation or predation (54,55).…”

“…One major selective event faced by M. gallisepticum after the jump into house finches was the evolution of host resistance to infection (Bonneaud et al 2011;Dowling et al 2020). The jump gave rise to an epidemic that spread quickly and is thought to have killed millions of house finches (Dhondt et al, 1998;Nolan et al, 1998).…”

The dynamics of evolutionary rescue from a novel pathogen threat in a host metapopulation

“…Infectious pathogens have the potential to drive the rapid extinction of entire populations [20][21][22] . Further, increased human transportation, land use changes, and global climate change have led to more frequent cases of the introduction or establishment of pathogens into new host species globally [23][24][25] . It is becoming clear that conservation biology must explicitly consider the potential for disease to impact species persistence 26,27 .…”