FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2022259611> ?p ?o ?g. }

• W2022259611 endingPage "322" @default.
• W2022259611 startingPage "320" @default.
• W2022259611 abstract "The bacterial pathogen Salmonella typhimurium resides within phagosomes in host cells and is able to deflect the host immune response. In this issue of Cell, Bader et al., 2005Bader M.W. Sanowar S. Daley M.E. Schneider A.R. Cho U. Xu W. Klevit R.E. LeMoual H. Miller S.I. Cell. 2005; 122 (this issue): 322-325Abstract Full Text Full Text PDF PubMed Scopus (387) Google Scholar decipher an elegant mechanism by which the PhoQ sensor kinase of Salmonella is switched on by host cationic antimicrobial peptides, leading to changes in gene expression that enable Salmonella to combat the host immune response. The bacterial pathogen Salmonella typhimurium resides within phagosomes in host cells and is able to deflect the host immune response. In this issue of Cell, Bader et al., 2005Bader M.W. Sanowar S. Daley M.E. Schneider A.R. Cho U. Xu W. Klevit R.E. LeMoual H. Miller S.I. Cell. 2005; 122 (this issue): 322-325Abstract Full Text Full Text PDF PubMed Scopus (387) Google Scholar decipher an elegant mechanism by which the PhoQ sensor kinase of Salmonella is switched on by host cationic antimicrobial peptides, leading to changes in gene expression that enable Salmonella to combat the host immune response. When a bacterium enters a host, certain events are triggered that will determine its fate. Different fates that might befall the microbe include destruction, passage through the host as a harmless transient, incorporation into the natural flora, or establishment of an infection with the initiation of host damage. The initial innate immune response of the host involves the activation of signaling pathways that recognize structurally conserved pathogen molecules using a series of receptors, in particular those of the Toll-like receptor (TLR) family (Miller et al., 2005Miller S.I. Ernst R.K. Bader M.W. Nat. Rev. Microbiol. 2005; 3: 36-46Crossref PubMed Scopus (716) Google Scholar). For example, the bacterial surface molecule lipopolysaccharide (LPS) engages TLR4, leading to the increased expression of numerous host defense genes including those encoding proinflammatory cytokines and chemokines, with the consequent marshalling of effectors of innate immunity to destroy or contain the microbe. The successful pathogen, however, recognizes environmental cues in the host and will remodel its metabolism and physiology to permit it to survive and grow in the host. For example, the small concentration of free iron in many hosts triggers production of bacterial iron acquisition systems (Bullen et al., 2005Bullen J.J. Rogers H.J. Spalding P.B. Ward C.G. FEMS Immunol. Med. Microbiol. 2005; 43: 325-330Crossref PubMed Scopus (195) Google Scholar). The study by Bader et al., 2005Bader M.W. Sanowar S. Daley M.E. Schneider A.R. Cho U. Xu W. Klevit R.E. LeMoual H. Miller S.I. Cell. 2005; 122 (this issue): 322-325Abstract Full Text Full Text PDF PubMed Scopus (387) Google Scholar in this issue of Cell sheds light on a particularly effective bacterial defense mechanism in the pathogen Salmonella typhimurium. The two-component sensor, PhoPQ, of Salmonella comprises a membrane bound sensor kinase PhoQ (which has a binding domain and a kinase/phosphatase domain) and a response regulator PhoP in the bacterial cytoplasm (see Figure 1). When the Salmonella bacterium encounters certain conditions (limiting concentrations of divalent cations or host cationic antimicrobial peptides), the PhoQ protein dimerizes and becomes autophosphorylated at a conserved histidine residue. The dimeric PhoQ protein then transfers the phosphate to an aspartate residue within PhoP, leading to increased affinity of PhoP for a conserved DNA binding motif and modulation of expression of target genes containing this conserved site (Castelli et al., 2000Castelli M.E. Garcia Vescovi E. Soncini F.C. J. Biol. Chem. 2000; 275: 22948-22954Crossref PubMed Scopus (93) Google Scholar). PhoPQ is found in a number of Gram-negative bacteria and is essential for the virulence of Gram-negative bacterial pathogens in humans and mice (Gunn, 2001Gunn J.S. J. Endotox. Res. 2001; 7: 57-62Crossref PubMed Google Scholar). Salmonella PhoPQ is activated when the bacteria are taken up into the phagosomes of host macrophages. In vitro experiments have shown that the PhoPQ system is activated by low concentrations of Ca2+, Mg2+, or Mn2+ ions (Castelli et al., 2000Castelli M.E. Garcia Vescovi E. Soncini F.C. J. Biol. Chem. 2000; 275: 22948-22954Crossref PubMed Scopus (93) Google Scholar). However, it is not intuitively obvious that PhoPQ would be activated inside host cells as most host tissues contain repressing (1–2 mM) concentrations of free Ca2+ and Mg2+, and the concentration of Ca2+ within phagosomes (0.4 to 0.6 mM) also is repressing (Christenson et al., 2002Christenson K.A. Myers J.T. Swanson J.A. J. Cell Sci. 2002; 115: 599-607PubMed Google Scholar). These observations suggest that, in vivo, Salmonella may be responding to a signal other than limiting divalent cation concentrations. Intriguingly, cationic antimicrobial peptides, which are key components of host innate immunity (Zasloff, 2002Zasloff M. Nature. 2002; 415: 389-395Crossref PubMed Scopus (6269) Google Scholar, Bowdish et al., 2005Bowdish D.M.E. Davidson D.J. Hancock R.E.W. Curr. Protein Pept. Sci. 2005; 6: 35-51Crossref PubMed Scopus (280) Google Scholar), induce upregulation of the Salmonella phoPQ operon (Bader et al., 2003Bader M.W. Navarre W.W. Shiau W. Nikaido H. Frye J.G. McClelland M. Fang F.C. Miller S.I. Mol. Microbiol. 2003; 50: 219-230Crossref PubMed Scopus (201) Google Scholar) as well as the Pseudomonas aeruginosa pmrAB operon, which encodes another type of bacterial two-component sensor (McPhee et al., 2003McPhee J.B. Lewenza S. Hancock R.E.W. Mol. Microbiol. 2003; 50: 205-219Crossref PubMed Scopus (305) Google Scholar). Bader et al., 2005Bader M.W. Sanowar S. Daley M.E. Schneider A.R. Cho U. Xu W. Klevit R.E. LeMoual H. Miller S.I. Cell. 2005; 122 (this issue): 322-325Abstract Full Text Full Text PDF PubMed Scopus (387) Google Scholar now reveal that these host cationic antimicrobial peptides bind directly to the binding domain of Salmonella’s PhoQ membrane bound sensor via an acidic patch that seems to overlap with the PhoQ binding domain for divalent cations (see Figure 1). Binding of these peptides activates the kinase activity of PhoQ, resulting in phosphorylation and activation of PhoP, which then alters the transcription of specific bacterial target genes. Using a sophisticated combination of genetic, structural, and biophysical approaches, Bader and colleagues construct a model in which the PhoQ binding domain of Salmonella interacts with negatively charged lipids in the outer leaflet of the bacterial cytoplasmic membrane via a divalent Mg2+ bridge (see Figure 1). Removal of Mg2+ ions or their displacement by cationic antimicrobial peptides induces a structural transition in PhoQ that is translated across the cytoplasmic membrane, promoting phosphorylation of PhoP. Cationic antimicrobial peptides, despite great diversity of structure, tend to fold into amphipathic structures that lie on the surface of the bacterial cytoplasmic membrane with their positive charges facing outwards; hence, they are ideally suited to interacting with the membrane-facing anionic patch of PhoQ. Cationic antimicrobial peptides are a ubiquitous component of the innate immune systems of complex eukaryotes: they are found in plants, insects, amphibians, crustaceans, and mammals, including humans. These antimicrobial peptides not only have direct antimicrobial activity but also are involved in the modulation of other innate immune pathways (Zasloff, 2002Zasloff M. Nature. 2002; 415: 389-395Crossref PubMed Scopus (6269) Google Scholar, Bowdish et al., 2005Bowdish D.M.E. Davidson D.J. Hancock R.E.W. Curr. Protein Pept. Sci. 2005; 6: 35-51Crossref PubMed Scopus (280) Google Scholar) because they can act as chemokines. In this capacity they stimulate host gene expression, selectively suppress endotoxemia/sepsis, and stimulate wound healing and angiogenesis. In humans, they are prominent components of dedicated anti-infective (phagocytic) cells and are also found in other cell types (myeloid precursor cells, epithelial cells, mast cells, keratinocytes, and lymphocytes), in other tissues (the mucosa, intestine, skin, oral cavity, cervix, lungs), and in bodily fluids (gastric juices, saliva, semen, sweat, plasma, airway surface liquid, and breast milk). The concentrations of these antimicrobial peptides vary from very high in sites where their action is likely to be direct—in the granules of phagocytes or the crypts of the intestine—to modest in locations such as mucosal surfaces where their immunomodulatory properties may be more important. Salmonella bacteria enter host cells by binding to the gastric mucosa and are taken up by a variety of host cell types including phagocytes. Once inside host cells, this pathogen resides in vesicles of host origin called Salmonella-containing vesicles and resists destruction. It is striking that Salmonella has evolved a mechanism that harnesses host antimicrobial peptides to switch on its own defense system, PhoPQ, which enables the pathogen to become resistant to the antimicrobial peptides as well as to other cationic defense molecules such as the antibiotic polymyxin. When PhoPQ is activated, the lipid A portion of LPS—which anchors LPS in the outer membrane of Gram-negative bacteria—becomes modified by aminoarabinose and fatty acids, which decreases the negative charge and fluidity of the bacterial outer membrane. This results in decreased binding and uptake of cationic antimicrobial peptides across the bacterial outer membrane, leading to resistance of Salmonella to these peptides. Modification of the lipid A portion of LPS by PhoPQ also reduces by up to 100-fold the ability of Salmonella LPS to induce host innate immunity via TLR4 (Kawasaki et al., 2004Kawasaki K. Ernst R.K. Miller S.I. J. Endotoxin Res. 2004; 10: 439-444Crossref PubMed Google Scholar), resulting in muting of the host immune response. Furthermore, the regulation by PhoPQ of more than 200 bacterial genes involved in chemotaxis/motility, drug resistance, transport, and heme biosynthesis indicates that a substantial shift in bacterial physiology is triggered by induction of this clever defense system (Minagawa et al., 2003Minagawa S. Ogasawara H. Kato A. Yamamoto K. Eguchi Y. Oshima T. Mori H. Ishihama A. Utsumi R. J. Bacteriol. 2003; 185: 3696-3702Crossref PubMed Scopus (121) Google Scholar)." @default.
• W2022259611 created "2016-06-24" @default.
• W2022259611 creator A5038654542 @default.
• W2022259611 creator A5066530115 @default.
• W2022259611 date "2005-08-01" @default.
• W2022259611 modified "2023-09-29" @default.
• W2022259611 title "Salmonella’s Sensor for Host Defense Molecules" @default.
• W2022259611 cites W1896469456 @default.
• W2022259611 cites W1953311373 @default.
• W2022259611 cites W1968820299 @default.
• W2022259611 cites W2011903713 @default.
• W2022259611 cites W2034541624 @default.
• W2022259611 cites W2047570111 @default.
• W2022259611 cites W2054602599 @default.
• W2022259611 cites W2073578515 @default.
• W2022259611 cites W2103590204 @default.
• W2022259611 cites W2137081432 @default.
• W2022259611 cites W2164806933 @default.
• W2022259611 cites W4243471842 @default.
• W2022259611 doi "https://doi.org/10.1016/j.cell.2005.07.023" @default.
• W2022259611 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16096052" @default.
• W2022259611 hasPublicationYear "2005" @default.
• W2022259611 type Work @default.
• W2022259611 sameAs 2022259611 @default.
• W2022259611 citedByCount "18" @default.
• W2022259611 countsByYear W20222596112012 @default.
• W2022259611 countsByYear W20222596112013 @default.
• W2022259611 countsByYear W20222596112014 @default.
• W2022259611 countsByYear W20222596112020 @default.
• W2022259611 countsByYear W20222596112021 @default.
• W2022259611 crossrefType "journal-article" @default.
• W2022259611 hasAuthorship W2022259611A5038654542 @default.
• W2022259611 hasAuthorship W2022259611A5066530115 @default.
• W2022259611 hasBestOaLocation W20222596111 @default.
• W2022259611 hasConcept C126831891 @default.
• W2022259611 hasConcept C2781065037 @default.
• W2022259611 hasConcept C523546767 @default.
• W2022259611 hasConcept C54355233 @default.
• W2022259611 hasConcept C86803240 @default.
• W2022259611 hasConcept C89423630 @default.
• W2022259611 hasConceptScore W2022259611C126831891 @default.
• W2022259611 hasConceptScore W2022259611C2781065037 @default.
• W2022259611 hasConceptScore W2022259611C523546767 @default.
• W2022259611 hasConceptScore W2022259611C54355233 @default.
• W2022259611 hasConceptScore W2022259611C86803240 @default.
• W2022259611 hasConceptScore W2022259611C89423630 @default.
• W2022259611 hasIssue "3" @default.
• W2022259611 hasLocation W20222596111 @default.
• W2022259611 hasLocation W20222596112 @default.
• W2022259611 hasOpenAccess W2022259611 @default.
• W2022259611 hasPrimaryLocation W20222596111 @default.
• W2022259611 hasRelatedWork W1498744261 @default.
• W2022259611 hasRelatedWork W1614430019 @default.
• W2022259611 hasRelatedWork W198468377 @default.
• W2022259611 hasRelatedWork W2000898433 @default.
• W2022259611 hasRelatedWork W2009068171 @default.
• W2022259611 hasRelatedWork W2068012419 @default.
• W2022259611 hasRelatedWork W2335684962 @default.
• W2022259611 hasRelatedWork W3180996806 @default.
• W2022259611 hasRelatedWork W4249153632 @default.
• W2022259611 hasRelatedWork W4249674358 @default.
• W2022259611 hasVolume "122" @default.
• W2022259611 isParatext "false" @default.
• W2022259611 isRetracted "false" @default.
• W2022259611 magId "2022259611" @default.
• W2022259611 workType "article" @default.