scholarly journals A comparative analysis of Caenorhabditis and Drosophila transcriptional changes in response to pathogen infection

2020 ◽  
Author(s):  
Robert L. Unckless ◽  
Patrick A. Lansdon ◽  
Brian D. Ackley
Keyword(s):  
Bacterial Pathogens ◽  
Innate Immune ◽  
Complete Analysis ◽  
Human Pathogens ◽  
Gram Negative ◽  
C Elegans ◽  
Evolutionary Changes ◽  
Transcriptional Changes ◽  
Invertebrate Models ◽  
Insight Into

AbstractDrosophila melanogaster and Caenorhabditis elegans are well-used invertebrate models for studying the innate immune system. The organisms are susceptible to bacterial pathogens that include Pseudomonas species, (entomophilia – Drosophila) or (aeruginosa – Caenorhabditis), E. faecalis and P. rettgeri, which are or are related to human pathogens. Further, the consequences of exposure to these pathogens, in terms of organismal survival, are roughly equivalent when compared. That is, worms and flies are more susceptible to infection by Pseudomonas than E. faecalis, whereas organismal survival on E. faecalis and P. rettgeri are roughly the same in both. To better understand how these organisms are coordinating their responses to these bacterial pathogens we examined transcriptomes in infected animals. We grouped our analysis based on protein orthology. Of the 3611 pairs analyzed, we found genes whose responses were conserved across the different species at a higher than expected rate for two of the three pathogens. Interestingly within the animals, genes with 1:1 orthologs between species behaved differently. Such genes were more likely to be expressed in D. melanogaster, and less likely to be expressed in C. elegans. From this analysis we found that the gene nucleobindin (nucb-1/NUCB1 in C. elegans and D. melanogaster, respectively) was upregulated in both species in response to Gram negative bacteria. We used RNAi to knock down nucb-1 and found the treated animals were more susceptible to infection by the Gram negative pathogen P. rettgeri than controls. These results provide insight into some of the conserved mechanisms of pathogen defense, but also suggest that these divergent organisms have evolved specific means to orchestrate the defense against pathogens.Article SummaryWe analyzed transcriptomic data from C. elegans and D. melanogaster to compare the expression of orthologous pairs of genes in response to bacterial pathogens. Our results indicated that only a handful of genes that are orthologous between species are differentially expressed in response to pathogens, but that the pattern of expression was different when comparing one-to-one orthologs versus those that are restricted to one of the two organisms. These results suggest that, although broad patterns of susceptibility to bacterial pathogens are conserved, the regulatory framework by which the organisms fight pathogens is less well conserved. Further our results suggest a more complete analysis of the evolutionary changes in organismal responses to pathogens is required.

scholarly journals Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella

2021 ◽  
Vol 11 ◽  
Author(s):  
Kei Amemiya ◽  
Jennifer L. Dankmeyer ◽  
Robert C. Bernhards ◽  
David P. Fetterer ◽  
David M. Waag ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Bacterial Pathogens ◽  
Innate Immune ◽  
Burkholderia Mallei ◽  
Toll Like Receptors ◽  
Wild Type ◽  
Gram Negative ◽  
Tier 1 ◽  
Biochemical Components ◽  
Schu S4

Successful bacterial pathogens have evolved to avoid activating an innate immune system in the host that responds to the pathogen through distinct Toll-like receptors (TLRs). The general class of biochemical components that activate TLRs has been studied extensively, but less is known about how TLRs interact with the class of compounds that are still associated with the live pathogen. Accordingly, we examined the activation of surface assembled TLR 2, 4, and 5 with live Tier 1 Gram-negative pathogens that included Yersinia pestis (plague), Burkholderia mallei (glanders), Burkholderia pseudomallei (melioidosis), and Francisella tularensis (tularemia). We found that Y. pestis CO92 grown at 28°C activated TLR2 and TLR4, but at 37°C the pathogen activated primarily TLR2. Although B. mallei and B. pseudomallei are genetically related, the former microorganism activated predominately TLR4, while the latter activated predominately TLR2. The capsule of wild-type B. pseudomallei 1026b was found to mitigate the activation of TLR2 and TLR4 when compared to a capsule mutant. Live F. tularensis (Ft) Schu S4 did not activate TLR2 or 4, although the less virulent Ft LVS and F. novicida activated only TLR2. B. pseudomallei purified flagellin or flagella attached to the microorganism activated TLR5. Activation of TLR5 was abolished by an antibody to TLR5, or a mutation of fliC, or elimination of the pathogen by filtration. In conclusion, we have uncovered new properties of the Gram-negative pathogens, and their interaction with TLRs of the host. Further studies are needed to include other microorganism to extend our observations with their interaction with TLRs, and to the possibility of leading to new efforts in therapeutics against these pathogens.

scholarly journals Analysis of the Caenorhabditis elegans innate immune response to Coxiella burnetii

2016 ◽  
Vol 23 (2) ◽  
pp. 111-127 ◽  
Author(s):  
James M Battisti ◽  
Lance A Watson ◽  
Myo T Naung ◽  
Adam M Drobish ◽  
Ekaterina Voronina ◽  
...  
Keyword(s):  
Immune Response ◽  
Caenorhabditis Elegans ◽  
Innate Immune Response ◽  
Coxiella Burnetii ◽  
Molecular Mechanisms ◽  
Q Fever ◽  
Innate Immune ◽  
Human Pathogens ◽  
C Elegans ◽  
Intestinal Distension

The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan. However, nematodes fed autoclave-killed CCB did not exhibit these symptoms. Although vertebrates detect C. burnetii via TLRs, pathologies in tol-1(–) mutant nematodes were indistinguishable from N2, and indicate nematodes do not employ this orthologue for detection of C. burnetii. sek-1(–) MAP kinase mutant nematodes succumbed to infection faster, suggesting that this signaling pathway plays a role in immune activation, as previously shown for orthologues in vertebrates during a C. burnetii infection. C. elegans daf-2(–) mutants are hyper-immune and exhibited significantly reduced pathological consequences during challenge. Collectively, these results demonstrate the utility of C. elegans for studying the innate immune response against C. burnetii and could lead to discovery of novel methods for prevention and treatment of disease in humans and livestock.

scholarly journals Transcriptomic signature on Hantavirus Cardiopulmonary Syndrome patients, reveals an increased interferon response as a hallmark of critically ill patients

2021 ◽  
Author(s):  
Grazielle E Ribeiro ◽  
Eduardo Duran-Jara ◽  
Ruth Perez ◽  
Analia Cuiza ◽  
Luis E Leon ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Fatal Outcome ◽  
Laboratory Data ◽  
Innate Immune ◽  
Interferon Response ◽  
Human Pathogens ◽  
Severe Condition ◽  
Transcriptomic Signature ◽  
Insight Into

New World hantaviruses are important human pathogens that can cause a severe zoonotic disease called hantavirus cardiopulmonary syndrome (HCPS). HCPS patients can progress quickly to a severe condition with respiratory failure and cardiogenic shock that can be fatal in 30% of the cases. The role of the host's immune responses in this progression towards HCPS remains elusive. In this study, 12 patients hospitalized with severe HCPS were analyzed using a transcriptome approach combined with clinical laboratory data to gain a better insight into factors associated with a severe clinical course. Patients were further classified in two levels of severity, a first group that required mechanical ventilation and vasoactive drugs (VM+VD) and a second group that also needed ECMO or died (ECMO/Fatal). Their transcriptional profile was compared during acute (early and late) and convalescent phases. Our results showed that overexpression of the interferon response is correlated with a worse (ECMO/Fatal) outcome and an increased viral load and proinflammatory cytokines in the early-acute-phase. This report provides insights into the differences in innate immune activation between severe patients that associates with different clinical outcomes, using a non-biased approximation.

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.

scholarly journals A Fish Galectin-8 Possesses Direct Bactericidal Activity

2020 ◽  
Vol 22 (1) ◽  
pp. 376
Author(s):  
Tengfei Zhang ◽  
Shuai Jiang ◽  
Li Sun
Keyword(s):  
Bactericidal Activity ◽  
Bacterial Pathogens ◽  
Bactericidal Effect ◽  
Immune Defense ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Animal Cells ◽  
Gram Negative ◽  
Tongue Sole ◽  
Wide Range

Galectins are a family of animal lectins with high affinity for β-galactosides. Galectins are able to bind to bacteria, and a few mammalian galectins are known to kill the bound bacteria. In fish, no galectins with direct bactericidal effect have been reported. In the present study, we identified and characterized a tandem repeat galectin-8 from tongue sole Cynoglossus semilaevis (designated CsGal-8). CsGal-8 possesses conserved carbohydrate recognition domains (CRDs), as well as the conserved HXNPR and WGXEE motifs that are critical for carbohydrate binding. CsGal-8 was constitutively expressed in nine tissues of tongue sole and up-regulated in kidney, spleen, and blood by bacterial challenge. When expressed in HeLa cells, CsGal-8 protein was detected both in the cytoplasm and in the micro-vesicles secreted from the cells. Recombinant CsGal-8 (rCsGal-8) bound to lactose and other carbohydrates in a dose dependent manner. rCsGal-8 bound to a wide range of gram-positive and gram-negative bacteria and was co-localized with the bound bacteria in animal cells. Lactose, fructose, galactose, and trehalose effectively blocked the interactions between rCsGal-8 and different bacteria. Furthermore, rCsGal-8 exerted potent bactericidal activity against some gram-negative bacterial pathogens by directly damaging the membrane and structure of the pathogens. Taken together, these results indicate that CsGal-8 likely plays an important role in the immune defense against some bacterial pathogens by direct bacterial interaction and killing.

On a tandem queueing model with identical service times at both counters, I

1979 ◽  
Vol 11 (3) ◽  
pp. 616-643 ◽  
Author(s):  
O. J. Boxma
Keyword(s):  
Waiting Times ◽  
Sufficient Conditions ◽  
Complete Analysis ◽  
Single Server ◽  
Stationary Distributions ◽  
In Series ◽  
Queues In Series ◽  
Service Times ◽  
Necessary And Sufficient ◽  
Insight Into

This paper considers a queueing system consisting of two single-server queues in series, in which the service times of an arbitrary customer at both queues are identical. Customers arrive at the first queue according to a Poisson process.Of this model, which is of importance in modern network design, a rather complete analysis will be given. The results include necessary and sufficient conditions for stationarity of the tandem system, expressions for the joint stationary distributions of the actual waiting times at both queues and of the virtual waiting times at both queues, and explicit expressions (i.e., not in transform form) for the stationary distributions of the sojourn times and of the actual and virtual waiting times at the second queue.In Part II (pp. 644–659) these results will be used to obtain asymptotic and numerical results, which will provide more insight into the general phenomenon of tandem queueing with correlated service times at the consecutive queues.

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