FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3120251112> ?p ?o ?g. }

• W3120251112 endingPage "3" @default.
• W3120251112 startingPage "1" @default.
• W3120251112 abstract "As vectors of microbial diseases in vertebrates, ticks are excellent at regulating bacterial proliferation in and around them. In a recent issue of Cell, Hayes et al., 2020Hayes B.M. Radkov A.D. Yarza F. Flores S. Kim J. Zhao Z. Lexa K.W. Marnin L. Biboy J. Bowcut V. et al.Ticks resist skin commensals with immune factor of bacterial origin.Cell. 2020; 183: 1562-1571.e12Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar reveal acarid toxins of bacterial origin that help eliminate microbes that are pathogenic to black-legged ticks but commensal to their vertebrate hosts. As vectors of microbial diseases in vertebrates, ticks are excellent at regulating bacterial proliferation in and around them. In a recent issue of Cell, Hayes et al., 2020Hayes B.M. Radkov A.D. Yarza F. Flores S. Kim J. Zhao Z. Lexa K.W. Marnin L. Biboy J. Bowcut V. et al.Ticks resist skin commensals with immune factor of bacterial origin.Cell. 2020; 183: 1562-1571.e12Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar reveal acarid toxins of bacterial origin that help eliminate microbes that are pathogenic to black-legged ticks but commensal to their vertebrate hosts. Ticks are blood-feeding parasites that are responsible for vectoring a wide variety of mammalian pathogens, including the bacterial etiological agents of granular anaplasmosis and Lyme disease. Their unique life history is sustained by a tightly regulated innate immune system, which allows them to tolerate populations of vertebrate pathogens while limiting the growth of their own pathogens that they invariably encounter during blood feeding (Kopáček et al., 2010Kopáček P. Hajdušek O. Burešová V. Daffre S. Tick innate immunity.in: Söderhäll K. Invertebrate Immunity. Springer, 2010: 137-162Crossref Scopus (72) Google Scholar). Most arthropods, including ticks, rely on an evolutionarily conserved and relatively limited repertoire of receptor and effector proteins that detect and eliminate invading bacterial pathogens (Schulenburg et al., 2007Schulenburg H. Boehnisch C. Michiels N.K. How do invertebrates generate a highly specific innate immune response?.Mol. Immunol. 2007; 44: 3338-3344Crossref PubMed Scopus (117) Google Scholar). Peptidoglycan, a polymer of β-1,4-linked sugars N-acetylmuramic acid and N-acetyl-d-glucosamine, is the major structural component of bacterial cell walls (Figure 1). Tetrapeptide (of four amino acids) side-chains attached to the muramic acid residues help cross-link peptidoglycan chains to form a mesh, protecting bacteria from osmotic damage and lysis (Figure 1). The exclusive association of peptidoglycan with bacteria makes it an ideal target for innate immunity molecules like lysozymes and peptidoglycan receptor proteins (PGRPs; Schulenburg et al., 2007Schulenburg H. Boehnisch C. Michiels N.K. How do invertebrates generate a highly specific innate immune response?.Mol. Immunol. 2007; 44: 3338-3344Crossref PubMed Scopus (117) Google Scholar). In addition, however, to the usual battery of peptidoglycan-sensing and degrading-enzymes found in most arthropods, the black-legged tick Ixodes scapularis (IS) displays an additional group of immunity proteins belonging to the domesticated amidase effector 2 (Dae2) family. These proteins are most closely related to the bacterial type VI amidase effector 2 (Tae2) proteins, which have been suggested to play a role in inter-bacterial competition, especially targeting Gram-negative bacteria (Chou et al., 2015Chou S. Daugherty M.D. Peterson S.B. Biboy J. Yang Y. Jutras B.L. Fritz-Laylin L.K. Ferrin M.A. Harding B.N. Jacobs-Wagner C. et al.Transferred interbacterial antagonism genes augment eukaryotic innate immune function.Nature. 2015; 518: 98-101Crossref PubMed Scopus (53) Google Scholar). Although the amidase domains in some PGRPs could point to an ancient case of horizontal gene transfer from bacteria, Dae2 amidases are one of the best documented cases of such a cross-domain transfer of immune proteins in arthropods. The demonstration of moderate antibacterial activity of Dae2Is against Borrelia burgdorferi, the etiological agent of Lyme disease in a previous study (Chou et al., 2015Chou S. Daugherty M.D. Peterson S.B. Biboy J. Yang Y. Jutras B.L. Fritz-Laylin L.K. Ferrin M.A. Harding B.N. Jacobs-Wagner C. et al.Transferred interbacterial antagonism genes augment eukaryotic innate immune function.Nature. 2015; 518: 98-101Crossref PubMed Scopus (53) Google Scholar), hinted at a broader immunological role for the protein in regulating bacterial proliferation in ticks. In the December 10th issue of Cell, Hayes et al., 2020Hayes B.M. Radkov A.D. Yarza F. Flores S. Kim J. Zhao Z. Lexa K.W. Marnin L. Biboy J. Bowcut V. et al.Ticks resist skin commensals with immune factor of bacterial origin.Cell. 2020; 183: 1562-1571.e12Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar reveal that Dae2 proteins in ticks form an important extension to the canonical antibacterial immune responses observed in most other arthropods (Figure 1). Starting with the evolutionary origin of the proteins, the authors first conducted a comparative analysis of the primary structure of Dae2 proteins from ticks and their cousins belonging to the bacterial Tae2 family. Upon further examination, the variation in the amino acid sequences corresponded to differences also in the tertiary structure, mainly in the loop regions surrounding the catalytic domain and the adjoining substrate-binding domain. Next, the authors conducted in silico analyses to assess the binding efficiency of both groups of proteins to peptidoglycan. The results led them to hypothesize that Dae2Is not only binds its substrate more tightly than the Tae2St (Tae2 from Salmonella enterica Typhi) but may have also evolved to target a wider range of potential pathogens than its bacterial cousin. To functionally assess the predicted differences in substrate-binding affinity, the authors analyzed the degradation products obtained from the action of Dae2Is and Tae2St on peptidoglycan purified from three bacterial strains: Gram- negative Escherichia coli, Gram-positive Staphylococcus epidermidis (mammalian skin commensal and therefore likely encountered by ticks during blood feeding), and Gram-positive Bacillus subtilis (a ubiquitous environmental bacterium that is not mammalian-skin-specific). While Tae2St was able to degrade Gram-negative peptidoglycan, it was unable to effectively degrade Gram-positive peptidoglycan. Dae2Is, however, was able to degrade peptidoglycan of both types, thereby confirming the in silico predictions for both protein families. The detection of amidase activity in Dae2Is against purified peptidoglycan does not automatically imply its ability to effectively eliminate intact bacterial cells under in vivo conditions. Based on their previous study that found Dae2Is to be present in the salivary glands and midgut of I. scapularis, the authors estimated its normal physiological concentration in the glands and then tested if Dae2Is could have a bacteriolytic or bacteriostatic effect at that concentration. They observed Dae2Is to be highly efficient at killing S. epidermidis, Staphylococcus hominis, and Corynebacterium propiquum—Gram-positive members of predominant commensal genera in human skin microbiomes (Grice et al., 2009Grice E.A. Kong H.H. Conlan S. Deming C.B. Davis J. Young A.C. Bouffard G.G. Blakesley R.W. Murray P.R. Green E.D. et al.NISC Comparative Sequencing ProgramTopographical and temporal diversity of the human skin microbiome.Science. 2009; 324: 1190-1192Crossref PubMed Scopus (1647) Google Scholar). However, they also observed that Dae2Is was not as effective against E. coli or B. burgdorferi, suggesting that it is unable to penetrate their outer membrane and gain access to the peptidoglycan layer (Figure 1). Interestingly, despite possessing a Gram-positive cell wall like many of the sensitive bacterial strains, the same levels of Dae2Is did not damage B. subtilis significantly. All bacteria share a common backbone of peptidoglycan, but seemingly minute differences in sidechains can significantly affect its protein-binding properties (Schleifer and Kandler, 1972Schleifer K.H. Kandler O. Peptidoglycan types of bacterial cell walls and their taxonomic implications.Bacteriol. Rev. 1972; 36: 407-477Crossref PubMed Google Scholar). The results indicate that Dae2Is may be more nuanced in its specificity than originally expected and is able to distinguish between different peptidoglycan subtypes. The authors tracked the localization and transcription of Dae2Is during blood feeding with an elegant approach that combined immunofluorescence confocal microscopy and quantitative PCR. They accurately localized Dae2Is in the salivary glands of ticks and tracked its secretion into the saliva using immunoblot analysis. For the last piece of the puzzle, they tracked the flow of the protein via the saliva into the bite site where they checked if the sera from exposed mice are immunoreactive to Dae2Is. Their results showed that Dae2Is made it from the salivary glands to the bite site and elicited a specific immune response in the host. The authors also observed that blood feeding in both nymph and adult ticks coincided with an upregulation of Dae2Is expression, which further supports a highly coordinated role of Dae2Is at the bite site during blood feeding. Although the immunological role played by Dae2Is in the salivary glands seemed obvious, the reason for its abundance in the midgut was not quite as clear. The authors hypothesized that the protein localized in the midgut probably served as a second barrier to infection by opportunistic pathogens on the host’s skin microbiome. To test this hypothesis, they injected ticks with ~100 S. epidermidis cells directly into the midgut through the anal pore. Ticks in the challenge assays were also injected with the neutralizing antibody which binds Dae2Is. The authors observed that ticks with inhibited Dae2Is were unable to limit the proliferation S. epidermidis, which likely led to the high mortality observed. The results suggest that the presence of Dae2 in the midgut is critical to control the inactivation of potential pathogens, especially following feeding. As their final and most compelling experiment, the authors wished to test if Dae2Is activity confers resistance against skin-associated microbes. They impaired Dae2Is translation in ticks using RNAi and blocked pre-existing proteins by immunizing mice with Dae2Is. The impairment of Dae2 activity in ticks corresponded with an increase in the absolute abundance of staphylococci, discontinuous feeding, and weight loss, compared to controls. The growth of S. epidermidis in the absence of Dae2Is is consistent with its ability to grow well in vertebrate blood (Nguyen et al., 2017Nguyen T.H. Park M.D. Otto M. Host response to Staphylococcus epidermidis colonization and infections.Front. Cell. Infect. Microbiol. 2017; 7: 90Crossref PubMed Scopus (57) Google Scholar). The authors conducted additional in vivo challenge assays involving the microinjection with combinations of S. epidermidis and anti-Dae2 antibodies into ticks. They observed that inoculation with S. epidermidis when Dae2Is activity was impaired, resulted in high tick mortality, providing further evidence that Dae2Is limits the proliferation of staphylococci and can have a substantial influence on tick health and fitness. Taken together, the work by Hayes et al. is a major breakthrough in understanding the broader immunological role of Dae2 proteins in ticks. Aside from opening the door to possibly several examples of “innovation transfers” in arthropods (Husnik and McCutcheon, 2018Husnik F. McCutcheon J.P. Functional horizontal gene transfer from bacteria to eukaryotes.Nat. Rev. Microbiol. 2018; 16: 67-79Crossref PubMed Scopus (189) Google Scholar), the study marks an important step in understanding the mechanism through which ticks control the proliferation of their opportunistic pathogens. Since blood feeding has evolved several times in the evolutionary history of insects alone, it is likely that other hematophagous arthropods may have independently evolved similar adaptations to modulate the bacterial populations they come in contact with. Future studies can focus on unraveling key, but overlooked, cases of horizontal transfer in blood-feeding insects, such as mosquitoes, fleas, and tsetse flies as well. The study also raises intriguing questions about the interplay between the skin microbiome and arthropod vectors of disease. Given the predominance of Gram-positive or Gram-negative bacteria in the skin microbiomes of different vertebrate groups (Ross et al., 2019Ross A.A. Rodrigues Hoffmann A. Neufeld J.D. The skin microbiome of vertebrates.Microbiome. 2019; 7: 79Crossref PubMed Scopus (50) Google Scholar), it could be interesting to test the functional implications of the variation among Dae2 proteins from different tick species. For example, are Dae2 sequences from different tick species specifically adapted to the dominant skin microbiome members of their respective vertebrate hosts? This study also calls for a deeper investigation of the defensive role of the mammalian skin microbiome in the prevention of arthropod-vectored diseases. Finally, and broadly, the study highlights the context-dependent nature of host-microbe interactions (Shaw et al., 2018Shaw D.K. Tate A.T. Schneider D.S. Levashina E.A. Kagan J.C. Pal U. Fikrig E. Pedra J.H.F. Vector immunity and evolutionary ecology: The harmonious dissonance.Trends Immunol. 2018; 39: 862-873Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar); while the tick is a vector of human disease, Hayes et al. demonstrate how the tables can be easily turned to reveal us to be vectors of tick disease. Ticks Resist Skin Commensals with Immune Factor of Bacterial OriginHayes et al.CellDecember 10, 2020In BriefHayes et al. demonstrate that bacteria on the skin of humans can be pathogenic to ticks, but blacklegged ticks have horizontally acquired a bacterial toxin—Dae2—that efficiently kills mammalian skin microbes. Dae2 is secreted into the tick digestive system and kills off skin-associated staphylococci during feeding, but not Borrelia burgdorferi, the bacterial cause of Lyme disease in humans. Full-Text PDF Open Archive" @default.
• W3120251112 created "2021-01-18" @default.
• W3120251112 creator A5017696143 @default.
• W3120251112 date "2021-01-01" @default.
• W3120251112 modified "2023-09-26" @default.
• W3120251112 title "Beating Them with Their Own Stick—Tick Uses Amidase of Bacterial Origin as Part of Its Immune Arsenal" @default.
• W3120251112 cites W1985727657 @default.
• W3120251112 cites W2000994574 @default.
• W3120251112 cites W2047774330 @default.
• W3120251112 cites W2151020563 @default.
• W3120251112 cites W2602034785 @default.
• W3120251112 cites W2770060362 @default.
• W3120251112 cites W2895072165 @default.
• W3120251112 cites W2946966924 @default.
• W3120251112 cites W3112026679 @default.
• W3120251112 doi "https://doi.org/10.1016/j.chom.2020.12.019" @default.
• W3120251112 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33444551" @default.
• W3120251112 hasPublicationYear "2021" @default.
• W3120251112 type Work @default.
• W3120251112 sameAs 3120251112 @default.
• W3120251112 citedByCount "0" @default.
• W3120251112 crossrefType "journal-article" @default.
• W3120251112 hasAuthorship W3120251112A5017696143 @default.
• W3120251112 hasBestOaLocation W31202511121 @default.
• W3120251112 hasConcept C18903297 @default.
• W3120251112 hasConcept C203014093 @default.
• W3120251112 hasConcept C2779620486 @default.
• W3120251112 hasConcept C523546767 @default.
• W3120251112 hasConcept C54355233 @default.
• W3120251112 hasConcept C65588867 @default.
• W3120251112 hasConcept C86803240 @default.
• W3120251112 hasConcept C8891405 @default.
• W3120251112 hasConcept C89423630 @default.
• W3120251112 hasConcept C90856448 @default.
• W3120251112 hasConceptScore W3120251112C18903297 @default.
• W3120251112 hasConceptScore W3120251112C203014093 @default.
• W3120251112 hasConceptScore W3120251112C2779620486 @default.
• W3120251112 hasConceptScore W3120251112C523546767 @default.
• W3120251112 hasConceptScore W3120251112C54355233 @default.
• W3120251112 hasConceptScore W3120251112C65588867 @default.
• W3120251112 hasConceptScore W3120251112C86803240 @default.
• W3120251112 hasConceptScore W3120251112C8891405 @default.
• W3120251112 hasConceptScore W3120251112C89423630 @default.
• W3120251112 hasConceptScore W3120251112C90856448 @default.
• W3120251112 hasIssue "1" @default.
• W3120251112 hasLocation W31202511121 @default.
• W3120251112 hasOpenAccess W3120251112 @default.
• W3120251112 hasPrimaryLocation W31202511121 @default.
• W3120251112 hasRelatedWork W1973887690 @default.
• W3120251112 hasRelatedWork W2064130613 @default.
• W3120251112 hasRelatedWork W2067909340 @default.
• W3120251112 hasRelatedWork W2085675240 @default.
• W3120251112 hasRelatedWork W2148912475 @default.
• W3120251112 hasRelatedWork W2271602123 @default.
• W3120251112 hasRelatedWork W2412501707 @default.
• W3120251112 hasRelatedWork W2556724797 @default.
• W3120251112 hasRelatedWork W2755784675 @default.
• W3120251112 hasRelatedWork W2071583921 @default.
• W3120251112 hasVolume "29" @default.
• W3120251112 isParatext "false" @default.
• W3120251112 isRetracted "false" @default.
• W3120251112 magId "3120251112" @default.
• W3120251112 workType "article" @default.