Host exposure history modulates the within-host advantage of virulence in a songbird-bacterium system

AbstractThe host immune response can exert strong selective pressure on pathogen virulence, particularly when host protection against reinfection is incomplete. Since emerging in house finch populations, the bacterial pathogen Mycoplasma gallisepticum (MG) has been increasing in virulence. Repeated exposure to low-doses of MG, a proxy for what birds likely experience while foraging, provides significant but incomplete protection against reinfection. Here we sought to determine if the within-host, pathogen load advantage of high virulence is mediated by the degree of prior pathogen exposure, and thus the extent of immune memory. We created variation in host immunity by experimentally inoculating wild-caught, MG-naïve house finches with varying doses and number of exposures of a single pathogen strain of intermediate virulence. Following recovery from priming exposures, individuals were challenged with one of three MG strains of distinct virulence. We found that the quantitative pathogen load advantage of high virulence was strongly mediated by the degree of prior exposure. The greatest within-host load advantage of virulence was seen in hosts given low-dose priming exposures, akin to what many house finches likely experience while foraging. Our results show that incomplete host immunity produced by low-level prior exposure can create a within-host environment that favors more virulent pathogens.

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

Scientific Reports ◽

10.1038/s41598-021-87464-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daisy E. Gates ◽

Molly Staley ◽

Luc Tardy ◽

Mathieu Giraudeau ◽

Geoffrey E. Hill ◽

...

Keyword(s):

Host Resistance ◽

Serum Antibody ◽

Bacterial Disease ◽

Free Living ◽

House Finches ◽

Pathogen Virulence ◽

Pathogen Load ◽

Virulent Strains ◽

Susceptible Populations ◽

Antibody Levels

AbstractQuantifying variation in the ability to fight infection among free-living hosts is challenging and often constrained to one or a few measures of immune activity. While such measures are typically taken to reflect host resistance, they can also be shaped by pathogen effects, for example, if more virulent strains trigger more robust immune responses. Here, we test the extent to which pathogen-specific antibody levels, a commonly used measure of immunocompetence, reflect variation in host resistance versus pathogen virulence, and whether these antibodies effectively clear infection. House finches (Haemorhous mexicanus) from resistant and susceptible populations were inoculated with > 50 isolates of their novel Mycoplasma gallisepticum pathogen collected over a 20-year period during which virulence increased. Serum antibody levels were higher in finches from resistant populations and increased with year of pathogen sampling. Higher antibody levels, however, did not subsequently give rise to greater reductions in pathogen load. Our results show that antibody responses can be shaped by levels of host resistance and pathogen virulence, and do not necessarily signal immune clearance ability. While the generality of this novel finding remains unclear, particularly outside of mycoplasmas, it cautions against using antibody levels as implicit proxies for immunocompetence and/or host resistance.

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Contrasting evolution of virulence and replication rate in an emerging bacterial pathogen

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901556116 ◽

2019 ◽

Vol 116 (34) ◽

pp. 16927-16932 ◽

Cited By ~ 3

Author(s):

Luc Tardy ◽

Mathieu Giraudeau ◽

Geoffrey E. Hill ◽

Kevin J. McGraw ◽

Camille Bonneaud

Keyword(s):

Host Resistance ◽

Bacterial Pathogen ◽

Mediating Effect ◽

Replication Rate ◽

House Finches ◽

Pathogen Virulence ◽

Virulence Evolution ◽

Evolution Of Virulence ◽

Immune Manipulation ◽

The Relationship

Host resistance through immune clearance is predicted to favor pathogens that are able to transmit faster and are hence more virulent. Increasing pathogen virulence is, in turn, typically assumed to be mediated by increasing replication rates. However, experiments designed to test how pathogen virulence and replication rates evolve in response to increasing host resistance, as well as the relationship between the two, are rare and lacking for naturally evolving host–pathogen interactions. We inoculated 55 isolates of Mycoplasma gallisepticum, collected over 20 y from outbreak, into house finches (Haemorhous mexicanus) from disease-unexposed populations, which have not evolved protective immunity to M. gallisepticum. We show using 3 different metrics of virulence (body mass loss, symptom severity, and putative mortality rate) that virulence has increased linearly over >150,000 bacterial generations since outbreak (1994 to 2015). By contrast, while replication rates increased from outbreak to the initial spread of resistance (1994 to 2004), no further increases have occurred subsequently (2007 to 2015). Finally, as a consequence, we found that any potential mediating effect of replication rate on virulence evolution was restricted to the period when host resistance was initially increasing in the population. Taken together, our results show that pathogen virulence and replication rates can evolve independently, particularly after the initial spread of host resistance. We hypothesize that the evolution of pathogen virulence can be driven primarily by processes such as immune manipulation after resistance spreads in host populations.

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Coxiella burnetii inhibits host immunity by a protein phosphatase adapted from glycolysis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2110877119 ◽

2021 ◽

Vol 119 (1) ◽

pp. e2110877119

Author(s):

Yong Zhang ◽

Jiaqi Fu ◽

Shuxin Liu ◽

Lidong Wang ◽

Jiazhang Qiu ◽

...

Keyword(s):

Phosphatase Activity ◽

Coxiella Burnetii ◽

Protein Phosphatase ◽

Bacterial Pathogen ◽

Sugar Metabolism ◽

Host Immunity ◽

Host Cells ◽

Functional Screening ◽

Type Iv ◽

Fructose 1,6 Bisphosphate

Coxiella burnetii is a bacterial pathogen that replicates within host cells by establishing a membrane-bound niche called the Coxiella-containing vacuole. Biogenesis of this compartment requires effectors of its Dot/Icm type IV secretion system. A large cohort of such effectors has been identified, but the function of most of them remain elusive. Here, by a cell-based functional screening, we identified the effector Cbu0513 (designated as CinF) as an inhibitor of NF-κB signaling. CinF is highly similar to a fructose-1,6-bisphosphate (FBP) aldolase/phosphatase present in diverse bacteria. Further study reveals that unlike its ortholog from Sulfolobus tokodaii, CinF does not exhibit FBP phosphatase activity. Instead, it functions as a protein phosphatase that specifically dephosphorylates and stabilizes IκBα. The IκBα phosphatase activity is essential for the role of CinF in C. burnetii virulence. Our results establish that C. burnetii utilizes a protein adapted from sugar metabolism to subvert host immunity.

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Characteristic of the bread wheat leaf rust pathogen virulence in the Saratov region conditions

The Agrarian Scientific Journal ◽

10.28983/asj.y2020i9pp40-44 ◽

2020 ◽

pp. 40-44

Author(s):

Sergey Nikolaevich Sibikeev ◽

Elmira Alexandrovna Konkova ◽

Maria Fedorovna Salmova

Keyword(s):

Bread Wheat ◽

Agricultural Research ◽

Plant Immunity ◽

Maximum Level ◽

Partial Loss ◽

Pathogen Virulence ◽

Winter Bread Wheat ◽

High Virulence ◽

Wheat Leaf ◽

Pathogen Populations

The studies were conducted in the Lababoratory of plant immunity Agricultural Research Institute for South-East Regions Russia. The samples of pathogen populations were collected from commercial and promising cultivars of spring and winter bread wheat at the end of their growing season at the maximum level of disease development in a field nursery. Then this inoculum's has been propagated on susceptible cultivars of bread wheat in the laboratory conditions. During three years of studies (2017-2019) 30 monopustules isolates has been studied. These studied isolates were avirulent to Thatcher near isogenic lines with genes Lr41, Lr42, Lr43+24, Lr53 and virulent to Lr1, Lr2a, Lr2b, Lr2c, Lr3, Lr3bg, Lr3ka, Lr10, Lr11, Lr12, Lr13, Lr14a, Lr14b, Lr15, Lr16, Lr17, Lr18, Lr21, lr22a, lr22b, lr25, lr28, LR 30, Lr32, Lr33, Lr34, Lr35, lr36, lr37, LR 38, Lr40, LR44, Lr45, LR b, LR W, LR Erph, LR Kanred, Lr57, Lr67. The significant variation for virulence was observed in lines with the Lr20, Lr23, Lr24, Lr26, Lr29, and Lr47 genes. The study of the P. triticina population structure in 2017-2019 revealed a partial loss of the effectiveness of the Lr47 gene. It was found that populations of P. triticina in 2017-2019 were characterized by high virulence.

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Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity

Food & Function ◽

10.1039/c9fo01357a ◽

2019 ◽

Vol 10 (9) ◽

pp. 5759-5767

Author(s):

Wan-Ting Lee ◽

Boon-Khai Tan ◽

Su-Anne Eng ◽

Gan Chee Yuen ◽

Kit Lam Chan ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Virulence Factors ◽

Black Sea ◽

Sea Cucumber ◽

Multidrug Resistant ◽

Host Immunity ◽

Bacterial Virulence ◽

Pathogen Virulence ◽

Multidrug Resistant Pathogens ◽

Holothuria Atra

A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity.

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Variation in Seroprevalence of Antibodies against Mycoplasma Gallisepticum and Avipoxvirus in Nine Species of Birds with Differential Access to Feeders

Avian Biology Research ◽

10.3184/175815617x15102264820747 ◽

2018 ◽

Vol 11 (1) ◽

pp. 7-11 ◽

Cited By ~ 1

Author(s):

Emily R. Vana ◽

Elizabeth R. Wrobel ◽

Travis E. Wilcoxen

Keyword(s):

Disease Transmission ◽

Mycoplasma Gallisepticum ◽

House Finches ◽

Single Location ◽

Bird Feeders ◽

Feeding Activities ◽

Avian Pox ◽

Species Specific ◽

Pathogen Exposure

Congregation of individuals at high densities is known to increase disease transmission and bird-feeding activities are specifically aimed at attracting many birds to a single location. We surveyed nine potential host species for evidence of infection by each Mycoplasma gallisepticum (MG) and Avipoxvirus, or avian pox. We also examined differences in pathogen exposure at sites with bird feeders and sites without bird feeders. Finally, we compared prevalence of birds with antibodies against MG and avian pox to those that showed physical signs of infection. To test for pathogen exposure, we used indirect enzyme-linked immunosorbent assays. We found species-specific disease dynamics, as House Finches Haemorhous mexicanus had a significantly greater likelihood of having antibodies against MG than any other species. Birds at sites with feeders were more likely to have antibodies against MG. Birds at sites with feeders were no more likely to have antibodies against avian pox, but seroprevalence of avian pox did differ significantly among species. Overall, our findings suggest differential exposure and immune responses to each pathogen among species and that feeders increase the exposure of individuals to MG but not to avian pox, offering valuable new insights into the role of bird feeding activities in disease transmission among birds.

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Feeder density enhances house finch disease transmission in experimental epidemics

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2017.0090 ◽

2018 ◽

Vol 373 (1745) ◽

pp. 20170090 ◽

Cited By ~ 12

Author(s):

Sahnzi C. Moyers ◽

James S. Adelman ◽

Damien R. Farine ◽

Courtney A. Thomason ◽

Dana M. Hawley

Keyword(s):

Radio Frequency Identification ◽

Disease Transmission ◽

Bacterial Pathogen ◽

Pathogen Transmission ◽

House Finch ◽

Resource Subsidies ◽

House Finches ◽

Bird Feeders ◽

Group Members ◽

Radio Frequency Identification Devices

Anthropogenic food provisioning of wildlife can alter the frequency of contacts among hosts and between hosts and environmental sources of pathogens. Despite the popularity of garden bird feeding, few studies have addressed how feeders influence host contact rates and disease dynamics. We experimentally manipulated feeder density in replicate aviaries containing captive, pathogen-naive, groups of house finches ( Haemorhous mexicanus ) and continuously tracked behaviours at feeders using radio-frequency identification devices. We then inoculated one bird per group with Mycoplasma gallisepticum (Mg), a common bacterial pathogen for which feeders are fomites of transmission, and assessed effects of feeder density on house finch behaviour and pathogen transmission. We found that pathogen transmission was significantly higher in groups with the highest density of bird feeders, despite a significantly lower rate of intraspecific aggressive interactions relative to the low feeder density groups. Conversely, among naive group members that never showed signs of disease, we saw significantly higher concentrations of Mg-specific antibodies in low feeder density groups, suggesting that birds in low feeder density treatments had exposure to subclinical doses of Mg. We discuss ways in which the density of garden bird feeders could play an important role in mediating the intensity of Mg epidemics. This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife'.

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Pathogen transmission from vaccinated hosts can cause dose-dependent reduction in virulence

10.1101/830570 ◽

2019 ◽

Author(s):

Richard I. Bailey ◽

Hans H. Cheng ◽

Margo Chase-Topping ◽

Jody K. Mays ◽

Osvaldo Anacleto ◽

...

Keyword(s):

Disease Transmission ◽

Infectious Virus ◽

Pathogen Transmission ◽

Transmission Dynamics ◽

Disease Spread ◽

Disease Development ◽

Disease Symptoms ◽

Pathogen Virulence ◽

Pathogen Load ◽

Dose Dependent

AbstractMany livestock and human vaccines are leaky as they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning as it increases vaccination coverage required to prevent disease spread, and can promote evolution of increased pathogen virulence. Despite leakiness, vaccination may reduce pathogen load, affecting disease transmission dynamics. However, the impacts on post-transmission disease development and infectiousness in contact individuals are unknown. Here, we use transmission experiments involving Marek’s disease virus in chickens to show that vaccination with a leaky vaccine substantially reduces viral load in both vaccinated individuals and unvaccinated contact individuals they infect. Consequently, contact birds are less likely to develop disease symptoms or die, show less severe symptoms, and shed less infectious virus themselves, when infected by vaccinated birds. These results highlight that even partial vaccination with a leaky vaccine can have unforeseen positive consequences in controlling the spread and symptoms of disease.

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Disentangling unspecific and specific transgenerational immune priming components in host-parasite interactions

10.1101/429498 ◽

2018 ◽

Cited By ~ 1

Author(s):

Frida Ben-Ami ◽

Christian Orlic ◽

Roland R. Regoes

Keyword(s):

Bacterial Pathogen ◽

Immune Memory ◽

High Dose ◽

Immune Priming ◽

Host Parasite Interactions ◽

Pasteuria Ramosa ◽

Wide Range ◽

Different Strains ◽

Host Parasite ◽

First Time

AbstractExposure to a pathogen primes many organisms to respond faster or more efficiently to subsequent exposures. Such priming can be unspecific or specific, and has been found to extend across generations. Disentangling and quantifying specific and unspecific effects is essential for understanding the genetic epidemiology of a system. By combining a large infection experiment and mathematical modeling, we disentangle different transgenerational effects in the crustacean model Daphnia magna exposed to different strains of the bacterial parasite Pasteuria ramosa. In the experiments, we exposed hosts to a high-dose of one of three parasite strains, and subsequently challenged their offspring with multiple doses of the same or a different strain, i. e. homologously or heterogously. We find that exposure to Pasteuria decreases the susceptibility of a host’s offspring by approximately 50%. This transgenerational protection is not larger for homologous than for heterologous parasite challenges. Our work represents an important contribution not only to the analysis of immune priming in ecological systems, but also to the experimental assessment of vaccines. We present for the first time an inference framework to investigate specific and unspecific effects of immune priming on the susceptibility distribution of hosts — effects that are central to understanding immunity and the effect of vaccines.Author summaryImmune memory is a feature of immune systems that forms the basis of vaccination. In opposition to textbook accounts, the ability to specifically remember previous exposures has been found to extend to invertebrates and shown to be able to be passed on from mother to off-spring, i. e. to be transgenerational. In this paper, we investigate the extent of this specificity in unprecedented detail in water fleas. We exposed water flea mothers to different strains of a bacterial pathogen and challenged their offspring with a wide range of doses of a strain that were either identical to (homologous) or different from (heterologous) the strain, to which the mother had been exposed. We find that, while exposure of the mother reduces the susceptibility of the offspring, this effect is not specific. This work outlines the limits of specific transgenerational immune memory in this invertebrate system.

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RNAi-Based Biofungicides as a Promising Next-Generation Strategy for Controlling Devastating Gray Mold Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21062072 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2072

Author(s):

Md Tabibul Islam ◽

Sherif M. Sherif

Keyword(s):

Gene Silencing ◽

Foliar Application ◽

Current Knowledge ◽

Gray Mold ◽

Host Immunity ◽

Double Stranded Rna ◽

Host Interactions ◽

Pathogen Virulence ◽

Fungal Genes ◽

Interfering Rna

Botrytis cinerea is one of the most critical agro-economic phytopathogens and has been reported to cause gray mold disease in more than 1000 plant species. Meanwhile, small interfering RNA (siRNA), which induce RNA interference (RNAi), are involved in both host immunity and pathogen virulence. B. cinerea has been reported to use both siRNA effectors and host RNAi machinery to facilitate the progression of gray mold in host species. Accordingly, RNAi-based biofungicides that use double-stranded RNA (dsRNA) to target essential fungal genes are considered an emerging approach for controlling devastating gray mold diseases. Furthermore, spray-induced gene silencing (SIGS), in which the foliar application of dsRNA is used to silence the pathogen virulence genes, holds great potential as an alternative to host-induced gene silencing (HIGS). Recently, SIGS approaches have attracted research interest, owing to their ability to mitigate both pre- and post-harvest B. cinerea infections. The RNAi-mediated regulation of host immunity and susceptibility in B. cinerea–host interactions are summarized in this review, along with the limitations of the current knowledge of RNAi-based biofungicides, especially regarding SIGS approaches for controlling gray mold diseases under field conditions.

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