scholarly journals Evolution of host resistance and damage-limiting mechanisms to an emerging bacterial pathogen

2018 ◽  
Author(s):  
Camille Bonneaud ◽  
Luc Tardy ◽  
Mathieu Giraudeau ◽  
Geoffrey Hill ◽  
Kevin McGraw ◽  
...  

Understanding how hosts minimise the cost of emerging infections has fundamental implications for epidemiological dynamics and the evolution of pathogen virulence. Despite this, few experimental studies conducted in natural populations have explicitly tested whether hosts evolve resistance, which prevents infections or reduces pathogen load through immune activation, or tolerance, which limits somatic damages without decreasing pathogen load. In addition, none have done so controlling for the virulence of the pathogen isolate used, despite critical effects on host responses to infection. Here, we conducted an experimental inoculation study to test whether eastern North American house finches (Haemorrhous mexicanus) have evolved resistance or tolerance to their emerging bacterial pathogen, Mycoplasma gallisepticum, using 55 distinct isolates of varying virulence. First, we show that peak pathogen loads, which occurred around 8 days post-inoculation, did not differ between experimentally inoculated finches from disease-exposed (eastern) versus unexposed (western) population. However, pathogen loads subsequently decreased faster and to a greater extent in finches from exposed populations, indicating that they were able to clear the infection through adaptive immune processes. Second, we found no between-population difference in the regression of clinical symptom severity on pathogen load; if tolerance had evolved then the slope of this regression is predicted to be shallower (less negative) in the exposed population. However, finches from exposed populations displayed lower symptom severity for a given pathogen load, suggesting that damage-limitation mechanisms have accompanied the evolution of immune clearance. These observations show that resistance and damage-limitation mechanisms - including, but not limited to the standard conceptualisation of tolerance - should not be seen as mutually exclusive. Nevertheless, we propose that host resistance is especially likely to evolve in response to pathogens such as M. gallisepticum that require virulence for successful infection and transmission.

Author(s):  
Stephen F Smagula ◽  
Helmet T Karim ◽  
Tamer S Ibrahim ◽  
Robert T Krafty ◽  
Sarah T Stahl ◽  
...  

Abstract Objectives A lack of “morningness” predicts greater depression symptom severity over time, including in a vulnerable group of older adults: family dementia caregivers (dCGs). Evidence regarding the neurobiological basis of these correlations is needed to guide future research towards biomarker-informed detection and prevention approaches. We therefore primarily aimed to identify simple resting-state biomarkers that correlated with a lack of “morningness” in dCGs. Method We examined 54 dCGs (mean age = 70, range: 61–84; 70% female) of whom 40% were definite “morning types” according to Composite Scale of Morningness (CSM). Using a 7 Tesla resting-state sequence, we compared the functional connectivity of nodes in networks previously implicated in depression (fronto-parietal, default mode, limbic, and salience) between caregivers who were and were not “morning types.” Results Correcting for voxel-wise comparisons, “morning-type” dCGs had less amygdala–posterior cingulate connectivity (Cohen’s d = −1.3), which statistically mediated ~32% of the association between the degree of “morningness” and lower depression severity. Post hoc analyses of CSM items found significant correlations, with both amygdala–posterior cingulate FC and depression severity, for 4/6 items pertaining to difficulty, 2/5 items pertaining to preference, and 0/2 items pertaining to typical patterns. Discussion Prior research shows that amygdala–posterior cingulate connectivity increases when allocating attention to peripheral aspects of negative emotional stimuli. As such, difficulty with morning activation may relate to the ongoing direction of focus around distressing content; in contrast, morning activity participation may serve to limit focus on distress. Replication and experimental studies are required to confirm these associations and their modifiability.


2017 ◽  
Vol 97 (1) ◽  
pp. 12-16 ◽  
Author(s):  
Ozer Calis ◽  
Cetin Cekic ◽  
Serhat Kara ◽  
Demet Celik Ertekin

Erwinia amylovora causes fire blight mainly on pear, apple and quince trees. This bacterial pathogen also infects other Rosaceous plants, such as blackberry and raspberry. A race structure was established between an isolate of E. amylovora and berries using 40 wild blackberry and 7 wild raspberry genotypes. In pathogenicity tests, wild blackberry and raspberry genotypes had three phenotypic reactions: enhanced susceptibility, moderate susceptibility and resistance. We noted a higher bacterial growth of over 300 × 109 cfu mL-1 in plants with enhanced susceptibility, with resistant genotypes showing a bacterial growth of around 150 × 109 cfu mL-1. These results are also associated with symptoms observed at 29 days post-inoculation. This resistance is being evaluated to control fire blight.


1999 ◽  
Vol 79 (4) ◽  
pp. 533-538 ◽  
Author(s):  
M. A. Miller

This paper discusses the new animal drug approval process regulated by the Center for Veterinary Medicine (CVM), Food and Drug Administration (FDA) of the United States. The Center for Veterinary Medicine of FDA considers two criteria in ensuring the human food safety of edible animal products: i) safety of the chemical residues and ii) for antimicrobial products, microbiological safety including changes in bacterial pathogen load and resistance pattern. The hazard associated with animal drug products of non-carcinogenic compounds is assessed by conducting a standard battery of toxicology test, whereas the hazard from the carcinogenic potential of compounds is evaluated based on structure, results of genetic toxicity tests, and toxicology studies. Post approval monitoring is carried out to ensure that the animal drugs are being used properly after their approval. Particular concern is given to those eliciting an "acute" toxic reaction at relatively low levels. The other aspect of food safety regulated by CVM of FDA is microbiological safety, especially to antimicrobial drugs used at subtherapeutic levels in feeds. The studies are designed by FDA to ensure that antibiotic treatment of food-producing animals does not alter pathogen load or resistance pattern of pathogens. Two studies are generally performed: i) the salmonella shedding study, which addresses the effect of drug treatment on the excretion of salmonella in the feces of animals artificially infected with salmonella; and ii) the coliform resistance study, which monitors the effect of the drug on the resistance pattern of E. coli present in the endogenous fecal flora. After a retrospective study of the microbiological safety over past 20 yr, CVM of FDA is planning to revise some microbiological safety studies with focuses on: i) pathogen load, pathogen excretion and microorganism resistance pattern at the time of slaughter; and ii) susceptibility studies on products that have utility in human medicine. Key words: Animal drug, food safety, antibiotic


1963 ◽  
Vol 117 (3) ◽  
pp. 497-508 ◽  
Author(s):  
Irving Gray

1. Lysine deficiency has been produced in rats by placing the weanling animals on an experimental diet in which gluten replaced the casein of the control diet. Both diets were complete in all other known requirements. 2. The resistance of the deficient animals to a subcutaneous challenge of several concentrations of B. anthracis spores, was decreased. Deaths occurred within 2 days post inoculation. 3. When lysine was added to the gluten diet to bring the total concentration to that of the control diet, the growth rate of the animals was maintained but a decrease in resistance remained, although not as great as on the gluten diet. 4. Changes in the tissues associated with lysine deficiency are reported. 5. It is not unreasonable to state that within the time frame of our experiments, the decreased ability of the RES of the host to clear the invading organism from the tissues and subsequently to break down the organism is a major factor of the decreased resistance of the lysine-deficient rats to anthrax.


1988 ◽  
Vol 25 (3) ◽  
pp. 183-192 ◽  
Author(s):  
D. H. Percy ◽  
M. A. Hayes ◽  
T. E. Kocal ◽  
Z. W. Wojcinski

Male and female Wistar rats 2 to 15 months of age were inoculated intranasally with sialodacryoadenitis (SDA) virus and killed at 8 to 21 days post-inoculation (PI). Submandibular glands were evaluated by light and electron microscopy, and levels of salivary gland epidermal growth factor (EGF) were quantitated by cytochemistry and competitive radioreceptor assay. Apical granules in the epithelial cells of the granular convoluted tubules (GCT) were selectively depleted during the acute and convalescent stages of the disease. In addition, levels of immunoreactive EGF were reduced in affected submandibular glands, especially at 8 to 14 days PI with SDA virus, but some evidence of EGF depletion was seen at up to 3 weeks PI. A corresponding transient depletion of EGF receptor reactive salivary EGF was seen between 1 and 3 weeks after experimental SDA infection. These studies suggest that a clinical (or subclinical) infection with SDA virus could have significant effects on experimental studies on EGF-dependent functions, including reproductive physiology and carcinogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daisy E. Gates ◽  
Molly Staley ◽  
Luc Tardy ◽  
Mathieu Giraudeau ◽  
Geoffrey E. Hill ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mônica Neli Alves ◽  
Juan Camilo Cifuentes-Arenas ◽  
Laudecir Lemos Raiol-Junior ◽  
Jesus Aparecido Ferro ◽  
Leandro Peña

Huanglongbing is a highly destructive citrus disease associated with “Candidatus Liberibacter asiaticus” (Las), a phloem−limited and non-culturable bacterium, naturally transmitted by the psyllid Diaphorina citri. Although diverse approaches have been used to understand the molecular mechanisms involved in the pathogen–host interaction, such approaches have focused on already infected and/or symptomatic plants, missing early events in the initial days post-inoculation. This study aimed to identify the time course of Las multiplication and whole-plant colonization immediately following inoculation by infected psyllids feeding for 2 days. Thus, the experimental approach was to track Las titers after psyllid inoculation in new shoots (NS) of Citrus × sinensis (susceptible), Murraya paniculata (partially resistant), and Bergera koenigii (fully resistant). Soon after psyllid removal, Las titers dropped until the 10–12th days in all three species. Following this, Las titers increased exponentially only in C. × sinensis and M. paniculata, indicating active bacterial multiplication. In C. × sinensis, Las reached a stationary phase at ∼5 log Las cells/g of tissue from the 40th day onward, while in M. paniculata, Las increased at a lower rate of up to ∼3 log Las cells/g of tissue between the 40th and 60th days, decreasing gradually thereafter and becoming undetectable from the 160th day onward. In B. koenigii, Las titers decreased from the start and remained undetectable. In C. × sinensis, an average of 2.6 log of Las cells/g of tissue was necessary for Las to move out of 50% of the NS in 23.6 days and to colonize the rest of the plant, causing a successful infection. Conversely, the probability of Las moving out of the NS remained below 50% in M. paniculata and zero in B. koenigii. To our knowledge, this is the first study on Las dynamics and whole-plant colonization during the earliest stages of infection. Identification of critical time-points for either successful multiplication or Las resistance may help to elucidate initial events of Las–host interactions that may be missed due to longer sampling intervals and at later stages of infection.


Author(s):  
A.J. Brownwright ◽  
S.R. Palli ◽  
G.F. Caputo ◽  
S.S. Sohi

Apoptosis is an active cellular self-destruction regulated by expression or repression of certain genes. Apoptosis can be caused by a variety of both external and internal stimuli. Whether these different stimuli that can cause apoptosis converge into a final pathway that leads to self-destruction is not known. This paper compares apoptosis caused by a baculovirus, an RNA-synthesis inhibitor and a protein-synthesis inhibitor.Inoculation of IPLB-SF-21 (SF-21) and FPMI-CF-203 (CF-203, Fig. 1, ) cells with Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV) and Choristoneura fumiferana multicapsid nuclear polyhedrosis virus (CfMNPV), respectively, results in successful infection as visualized by formation of occlusion bodies (OBs). However, inoculation of CF-203 cells with AcMNPV, or SF-21 cells with CFMNPV, is unsuccessful and no OBs are seen. Inoculation of CF-203 cells with AcMNPV results in premature lysis of cells beginning at 12 hr post-inoculation (pi) and most of the cells are lysed by 48 hr pi.


Agriculture ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 573
Author(s):  
Nkulu Kabange Rolly ◽  
Qari Muhammad Imran ◽  
Hyun-Ho Kim ◽  
Nay Chi Aye ◽  
Adil Hussain ◽  
...  

Bacterial leaf blight (BLB), a vascular disease caused by Xanthomonasoryzae pv. oryzae (Xoo), induces a significant reduction in rice yield in severe epidemics. This study investigated the transcriptional regulation of the OsDHODH1 gene in rice cultivars exposed to the Xoo K3 isolate. The symptoms were monitored on a daily basis, and the lesion length of inoculated rice plants was scored 21 days post inoculation (dpi). The most resistant and the highly susceptible cultivars were used for gene expression analysis. The dihydroorotate dehydrogenase (DHODH) domain is shared by many proteins in different plant species, and in Arabidopsis, this protein is encoded by the AtPYD1 gene. To investigate the functional role of the OsDHODH1 gene under bacterial infection, we inoculated the Arabidopsispyd1-2 knockout (atpyd1-2) plants, lacking the AtPYD1 gene (orthologous gene of the rice OsDHODH1), with Pseudomonassyringae pv. tomato (Pst) DC3000 vir, and the phenotypic response was scored 9 dpi. Results show that OsDHODH1 was upregulated in Tunnae, the most resistant rice cultivar but downregulated in IRAT112, the highly susceptible rice cultivar. In addition, Tunnae, Sipi and NERICA-L14 exhibited a durable resistance phenotype towards Xoo K3 isolate 21 dpi. Moreover, the expression of OsPR1a and OsPR10b (the rice pathogenesis inducible genes) was significantly upregulated in Tunnae, while being suppressed in IRAT112. Furthermore, the atpyd1-2 plants exhibited a high susceptibility towards Pst DC3000 vir. AtPR1 and AtPR2 (the Arabidopsis pathogenesis inducible genes) transcripts decreased in the atpyd1-2 plants compared to Col-0 (wild type) plants. Due to the above, OsDHODH1 and AtPYD1 are suggested to be involved in the basal adaptive response mechanisms towards bacterial pathogen resistance in plants.


2021 ◽  
Author(s):  
Anita Talbot ◽  
Laura Gargan ◽  
Grainne Moran ◽  
Louis Prudent ◽  
Ian O'Connor ◽  
...  

Abstract Amoebic Gill Disease (AGD), caused by the protozoan extracellular parasite Paramoeba perurans, is a disease affecting Atlantic salmon (Salmo salar) aquaculture. Many studies to date have investigated the pathogenesis of ADG focusing on the host immune response in the gill after the appearance of clinical symptoms. This study investigated the gill transcriptomic profile of pre-clinical AGD using RNA-sequencing (RNA-seq) technology. RNA-seq libraries generated at 4, 7, 14 and 16 days post inoculation (dpi) identified 29,357 Differentially Expressed Genes (DEGs). RNA-seq data was validated using real-time, quantitative PCR (qPCR) analysis of 10 selected immune genes. DEGs mapped to 224 Gene Ontology (GO) terms, 27 reference pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and 15 Reactome Gene Sets. Immune suppression was evident at 7 dpi, prior to there being any evidence of ADG on the gill, involving signalling pathways for interleukins, Nod-like receptors, B-cell and T-cell receptors, and the differentiation of Th1/Th2 and Th17 cells. The results of this study suggest a mechanism for how N. perurans circumvents the host immune response to establish a successful infection, and could potentially lead to the development of novel strategies for AGD mitigation or prevention in aquaculture.


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