scholarly journals Mutation, selection, and quantitative genetic architecture of susceptibility to bacterial pathogens in C. elegans

2021 ◽  
Author(s):  
Lindsay M. Johnson ◽  
Sayran Saber ◽  
Md. Monjurul Islam Rifat ◽  
Sydney Rouse ◽  
Charles F. Baer
Keyword(s):  
Genetic Architecture ◽  
Balancing Selection ◽  
Bacterial Pathogens ◽  
Complex Trait ◽  
Competitive Fitness ◽  
E Coli ◽  
C Elegans ◽  
Quantitative Genetic ◽  
Fitness Tradeoffs ◽  
Selection Of

AbstractUnderstanding the evolutionary and genetic underpinnings of susceptibility to pathogens is of fundamental importance across a wide swathe of biology. Much theoretical and empirical effort has focused on genetic variants of large effect, but pathogen susceptibility often appears to be a polygenic complex trait. Here we investigate the quantitative genetics of survival over 120 hours of exposure (“susceptibility”) of C. elegans to three bacterial pathogens of varying virulence, along with the non-pathogenic OP50 strain of E. coli. We compare the genetic (co)variance input by spontaneous mutations accumulated under minimal selection to the standing genetic (co)variance in a set of ∼50 wild isolates. Three conclusions emerge. First, with one exception, mutations increase susceptibility to pathogens, and susceptibility is uncorrelated with fitness in the absence of pathogens. Second, the orientation in trait space of the heritable (co)variance of wild isolates is sufficiently explained by mutation. However, pathogen susceptibility is clearly under purifying, apparently directional, selection of magnitude similar to that of competitive fitness in the MA conditions. The results provide no evidence for fitness tradeoffs between pathogen susceptibility and fitness in the absence of pathogens, nor that balancing selection is important in maintaining genetic variation for susceptibility to these bacterial pathogens.

scholarly journals Balancing selection of the Intracellular Pathogen Response in natural Caenorhabditis elegans populations

2019 ◽  
Author(s):  
Lisa van Sluijs ◽  
Kobus J. Bosman ◽  
Frederik Pankok ◽  
Tatiana Blokhina ◽  
Joost A. G. Riksen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Balancing Selection ◽  
Model Organism ◽  
Evolutionary Strategies ◽  
Intracellular Pathogen ◽  
C Elegans ◽  
Pathogen Response ◽  
Orsay Virus ◽  
Selection Of

AbstractBackgroundGenetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation present for an antiviral pathway, the Intracellular Pathogen Response (IPR), underlying susceptibility to Orsay virus in the model organism Caenorhabditis elegans. The IPR involves transcriptional activity of 80 genes including the pals-genes. The pals-genes form an expanded gene family which hints they could be shaped by an evolutionary selective pressure. Here we examine the genetic variation in the pals-family for traces of selection and explore the molecular and phenotypic effects of having distinct pals-gene alleles.ResultsGenetic analysis of 330 world-wide C. elegans strains reveals that genetic diversity within the IPR-related pals-genes can be categorized in a few haplotypes worldwide. Importantly, two key-IPR regulators, pals-22 and pals-25, are in a genomic region carrying signatures of balancing selection. Therefore, distinct pals-22/pals-25 alleles have been maintained in C. elegans populations over time, which suggests different evolutionary strategies exist in IPR regulation. We investigated the IPR by infecting two C. elegans strains that represent distinct pals-22/pals-25 haplotypes, N2 and CB4856, with Orsay virus to determine their susceptibility and transcriptional response to infection. Our data suggests that regulatory genetic variation underlies constant high activity of IPR genes in CB4856 which could determine the host transcriptional defense. We found that CB4856 shows initially lower viral susceptibility than N2. High basal IPR expression levels might help counteract viral infection directly, whereas N2-like strains that need to activate the IPR genes first may have a slower response. Nevertheless, most wild strains harbor N2-like alleles for the pals-genes.ConclusionsOur work provides evidence for balancing genetic selection of immunity genes in C. elegans and illustrated how this may shape the transcriptional defense against pathogens. The transcriptional and genetic data presented in this study therefore provide a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.

scholarly journals Mutation, selection, and the prevalence of the C. elegans mortal germline phenotype

2021 ◽  
Author(s):  
Sayran Saber ◽  
Michael Snyder ◽  
Moein Rajaei ◽  
Charles F. Baer
Keyword(s):  
Mutation Rate ◽  
Balancing Selection ◽  
Natural Populations ◽  
Point Estimate ◽  
Temperature Dependent ◽  
Competitive Fitness ◽  
C Elegans

C. elegans strains with the mortal germline (Mrt) phenotype become progressively sterile over the course of a few tens of generations. Mrt is proximately controlled epigenetically, and is typically temperature-dependent, being penetrant at temperatures near the upper range of C. elegans' tolerance. Previous studies have suggested that Mrt presents a relatively large mutational target, and that Mrt is not uncommon in natural populations of C. elegans. The Mrt phenotype is not monolithic. Some strains exhibit a strong Mrt phenotype, in which individuals invariably become sterile over a few generations, whereas other strains show a weaker (less penetrant) phenotype in which the onset of sterility is slower and more stochastic. We present results in which we (1) quantify the rate of mutation to the Mrt phenotype, and (2) quantify the frequency of Mrt in a collection of 95 wild isolates. Over the course of ~16,000 meioses, we detected one mutation to a strong Mrt phenotype, resulting in a point estimate of the mutation rate UMrt 6 10-5/genome/generation. We detected no mutations to a weak Mrt phenotype. 5/95 wild isolates had a strong Mrt phenotype, and although quantification of the weak Mrt phenotype is inexact, the weak Mrt phenotype is not rare in nature. We estimate a strength of selection against mutations conferring the strong Mrt phenotype 0.1%, similar to selection against mutations affecting competitive fitness. The appreciable frequency of weak Mrt variants in nature combined with the low mutation rate suggests that Mrt may be maintained by balancing selection.

scholarly journals Long-Term Metabolomics Reference Material

2021 ◽  
Author(s):  
Goncalo J Gouveia ◽  
Amanda O Shaver ◽  
Briana M Garcia ◽  
Alison M Morse ◽  
Erik C Andersen ◽  
...  
Keyword(s):  
Quality Control ◽  
Extraction Process ◽  
Biologically Relevant ◽  
E Coli ◽  
C Elegans ◽  
Nmr Data ◽  
Analytical Platforms ◽  
Metabolite Extraction ◽  
Selection Of

The use of quality control samples in metabolomics ensures data quality, reproducibility and comparability between studies, analytical platforms and laboratories. Long-term, stable and sustainable reference materials (RMs) are a critical component of the QA/QC system, however, the limited selection of currently available matrix matched RMs reduce their applicability for widespread use. To produce a RM in any context, for any matrix that is robust to changes over the course of time we developed IBAT (Iterative Batch Averaging meThod). To illustrate this method, we generated 11 independently grown E. coli batches and made a RM over the course of 10 IBAT iterations. We measured the variance of these materials by NMR and showed that IBAT produces a stable and sustainable RM over time. This E. coli RM was then used as food source to produce a C. elegans RM for a metabolomics experiment. The metabolite extraction of this material alongside 41 independently grown individual C. elegans samples of the same genotype, allowed to estimate the proportion of sample variation in pre-analytical steps. From the NMR data, we found that 40% of the metabolite variance is due to the metabolite extraction process and analysis and 60% is due to sample-to-sample variance. The availability of RMs in untargeted metabolomics is one of the predominant needs of the metabolomics community that reach beyond quality control practices. IBAT addresses this need by facilitating the production of biologically relevant RMs and increasing their widespread use.

scholarly journals Bdellovibrio bacteriovorus protects Caenorhabditis elegans from bacterial pathogens

Fine Focus ◽  
2014 ◽  
Vol 1 (1) ◽  
pp. 51-61
Author(s):  
Elizabeth A. B. Emmert ◽  
Zachary M. Haupt ◽  
Katherine M. Pflaum ◽  
Jennifer L. Lasbury ◽  
Justin P. McGrath ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Therapeutic Agent ◽  
Bacterial Pathogens ◽  
Bdellovibrio Bacteriovorus ◽  
Gram Negative ◽  
E Coli ◽  
C Elegans ◽  
K 12 ◽  
And Control ◽  
Worm Gut

Bdellovibrio bacteriovorus is a naturally predatory bacterium that multiplies inside Gram negative prey bacteria. There is much interest in using Bdellovibrio as a living antibiotic to control infections by Gram negative pathogens. In recent years Caenorhabditis elegans has proven to be an attractive animal model of bacterial pathogenesis for a range of pathogens. We have used the C. elegans animal pathogenesis model to examine the ability of B. bacteriovorus to protect nematodes from four bacterial pathogens. In all cases, nematodes treated with B. bacteriovorus and the pathogen survived at a significantly higher level than nematodes treated with the pathogen alone. Treatment with B. bacteriovorus alone was nontoxic to the worms. We monitored the persistence of E. coli K-12 and E. coli OP50 in both B. bacteriovorus treated nematodes and control nematodes. E. coli K-12 levels were significantly lower in B. bacteriovorus treated nematodes than in control nematodes one day after Bdellovibrio exposure and E. coli K-12 was eliminated from the worm gut two days faster in B. bacteriovorus treated nematodes. E. coli OP50 also demonstrated significantly lower levels in B. bacteriovorus treated nematodes and faster elimination from the worm gut. The successful use of B. bacteriovorus as a therapeutic agent in C. elegans indicates that it may be useful as a living antibiotic in other animal systems.

The Study of Bacillus Subtils Antimicrobial Activity on Some of the Pathological Isolates

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Hussein A Kadhum ◽  
Thualfakar H Hasan2
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Bacillus Subtilis ◽  
Bacterial Growth ◽  
Broad Spectrum ◽  
Inhibitory Activity ◽  
Bacterial Pathogens ◽  
Inhibitory Ability ◽  
Selection Of

The study involved the selection of two isolates from Bacillus subtilis to investigate their inhibitory activity against some bacterial pathogens. B sub-bacteria were found to have a broad spectrum against test bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. They were about 23-30 mm and less against Klebsiella sp. The sensitivity of some antibodies was tested on the test samples. The results showed that the inhibitory ability of bacterial growth in the test samples using B. subtilis extract was more effective than the antibiotics used.

The Characterization of Antibiotic Resistance of Bacterial Isolates from Intensive Care Unit Patient Samples in a University Affiliated Hospital in Romania

2019 ◽  
Vol 70 (5) ◽  
pp. 1778-1783
Author(s):  
Andreea-Loredana Golli ◽  
Floarea Mimi Nitu ◽  
Maria Balasoiu ◽  
Marina Alina Lungu ◽  
Cristiana Cerasella Dragomirescu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Bacterial Pathogens ◽  
Resistance Rate ◽  
Resistance Pattern ◽  
Bacterial Isolates ◽  
E Coli ◽  
Acinetobacter Spp ◽  
Almost All ◽  
Klebsiella Spp

To determine the resistance pattern of bacterial pathogens involved in infections of the patients aged between 18-64 years, admitted in a ICU from a 1518-bed university-affiliated hospital. A retrospective study of bacterial pathogens was carried out on 351 patients aged between 18-64 years admitted to the ICU, from January to December 2017. In this study there were analysed 469 samples from 351 patients (18-64 years). A total of 566 bacterial isolates were obtained, of which 120 strains of Klebsiella spp. (35.39%%), followed by Nonfermenting Gram negative bacilli, other than Pseudomonas and Acinetobacter (NFB) (75- 22.12%), Acinetobacter spp. (53 - 15.63%), Pseudomonas aeruginosa and Proteus (51 - 15.04%), and Escherichia coli (49 - 14.45%). The most common isolates were from respiratory tract (394 isolates � 69.61%). High rates of MDR were found for Pseudomonas aeruginosa (64.70%), MRSA (62.65%) and Klebsiella spp. (53.33%), while almost all of the isolated NFB strains were MDR (97.33%). There was statistic difference between the drug resistance rate of Klebsiella and E. coli strains to ceftazidime and ceftriaxone (p[0.001), cefuroxime (p[0.01) and to cefepime (p[0.01). The study revealed an alarming pattern of antibiotic resistance in the majority of ICU isolates.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

Sign in / Sign up

Export Citation Format

Share Document