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Exploiting genomics to discover new antibiotics
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This review is an excellent summary of the numerous ways genomics has advanced the antimicrobial drug discovery process. It also underscores the broad gap that still exists between discovery of lead compounds and obtaining the successful end drug.
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McDevitt D., Rosenberg M. Exploiting genomics to discover new antibiotics. Trends Microbiol. 9:2001;611-617. This review is an excellent summary of the numerous ways genomics has advanced the antimicrobial drug discovery process. It also underscores the broad gap that still exists between discovery of lead compounds and obtaining the successful end drug.
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Trends Microbiol
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McDevitt, D.1
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2
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0034770090
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In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics
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This study illustrates the potential for finding additional sources of antibiotics and provides a plausible explanation for why probiotic bacteria are so beneficial.
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Pinchuk I.V., Bressollier P., Verneuil B., Fenet B., Sorokulova I.B., Megraud F., Urdaci M.C. In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics. Antimicrob Agents Chemother. 45:2001;3156-3161. This study illustrates the potential for finding additional sources of antibiotics and provides a plausible explanation for why probiotic bacteria are so beneficial.
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Antimicrob Agents Chemother
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Pinchuk, I.V.1
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Sorokulova, I.B.5
Megraud, F.6
Urdaci, M.C.7
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0034752042
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How many antibiotics are produced by the genus Streptomyces?
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Watve M.G., Tickoo R., Jog M.M., Bhole B.D. How many antibiotics are produced by the genus Streptomyces? Arch Microbiol. 176:2001;386-390.
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Arch Microbiol
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Watve, M.G.1
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Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding d-Ala-d-Ala
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0035943435
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Selective cleavage of d-Ala-d-Lac by small molecules: Re-sensitizing resistant bacteria to vancomycin
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This is an excellent example of the new line of augmenting drugs that enhance antibiotic action by resensitizing the bacteria to the antibiotic. The authors screened combinatorial libraries to identify small molecules capable of cleaving altered cell-wall peptidoglycan precursor peptides. The resulting lead compounds combined with vancomycin were found to resensitize vancomycin-resistant staphylococci to the antibiotic.
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Chiosis G., Boneca I.G. Selective cleavage of d-Ala-d-Lac by small molecules: re-sensitizing resistant bacteria to vancomycin. Science. 293:2001;1484-1487. This is an excellent example of the new line of augmenting drugs that enhance antibiotic action by resensitizing the bacteria to the antibiotic. The authors screened combinatorial libraries to identify small molecules capable of cleaving altered cell-wall peptidoglycan precursor peptides. The resulting lead compounds combined with vancomycin were found to resensitize vancomycin-resistant staphylococci to the antibiotic.
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Science
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Chiosis, G.1
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Rapid killing of Streptococcus pneumoniae with a bacteriophage cell wall hydrolase
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In this study, the authors continue to illustrate (see [7••] ) the powerful potential of using a bacteriophage enzyme to selectively eliminate antibiotic-resistant pneumococci.
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Loeffler J.M., Nelson D., Fischetti V.A. Rapid killing of Streptococcus pneumoniae with a bacteriophage cell wall hydrolase. Science. 294:2001;2170-2172. In this study, the authors continue to illustrate (see [7••] ) the powerful potential of using a bacteriophage enzyme to selectively eliminate antibiotic-resistant pneumococci.
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Science
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Loeffler, J.M.1
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0035957329
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Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme
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This is the first demonstration of the prophylactic use of lytic enzymes from bacteriophages to selectively kill pathogenic bacteria in a mouse model. The authors use a purified bacteriophage lysin to rapidly eliminate streptococci, including antibiotic-resistant strains, present in the nasopharynx of mice without affecting the normal indigenous microflora.
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Nelson D., Loomis L., Fischetti V.A. Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme. Proc Natl Acad Sci USA. 98:2001;4107-4112. This is the first demonstration of the prophylactic use of lytic enzymes from bacteriophages to selectively kill pathogenic bacteria in a mouse model. The authors use a purified bacteriophage lysin to rapidly eliminate streptococci, including antibiotic-resistant strains, present in the nasopharynx of mice without affecting the normal indigenous microflora.
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Proc Natl Acad Sci USA
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Nelson, D.1
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Merril, C.R.1
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Adhya, S.7
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A protein antibiotic in the phage Qb virion: Diversity in lysis targets
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Bernhardt T.G., Wang I.N., Struck D.K., Young R. A protein antibiotic in the phage Qb virion: diversity in lysis targets. Science. 292:2001;2326-2329.
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Science
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Bernhardt, T.G.1
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This study demonstrates the potential power of using pathogen-specific bacteriophage to rescue bacteremic mice from lethal challenge with antibiotic-resistant enterococci. The authors show that administration of a single injection of phage preparation 45 min after challenge rescued 100% of the animals. Even delaying injection until all the animals were moribund still rescued 50% of animals.
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Biswas B., Adhya S., Washart P., Paul B., Trostel A.N., Powell B., Carlton R., Merril C.R. Bacteriophage therapy rescues mice bacteremic from a clinical isolate of vancomycin-resistant Enterococcus faecium. Infect Immun. 70:2002;204-210. This study demonstrates the potential power of using pathogen-specific bacteriophage to rescue bacteremic mice from lethal challenge with antibiotic-resistant enterococci. The authors show that administration of a single injection of phage preparation 45 min after challenge rescued 100% of the animals. Even delaying injection until all the animals were moribund still rescued 50% of animals.
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Biswas, B.1
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This review documents the enormous impact veterinary use of antibiotics has had on the development and spread of antibiotic resistance in bacteria.
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Teuber M. Veterinary use and antibiotic resistance. Curr Opin Microbiol. 4:2001;493-499. This review documents the enormous impact veterinary use of antibiotics has had on the development and spread of antibiotic resistance in bacteria.
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Curr Opin Microbiol
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Teuber, M.1
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12
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Occurrence and diversity of tetracycline resistance genes in lagoons and groundwater underlying two swine production facilities
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This study demonstrates the direct correlation of agricultural use of antibiotics and the presence and spread via groundwater of diverse antibiotic resistance genes in the bacteria of gastrointestinal origin and in the indigenous soil microbiota.
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Chee-Sanford J.C., Aminov R.I., Krapac I.J., Garrigues-Jeanjean N., Mackie R.I. Occurrence and diversity of tetracycline resistance genes in lagoons and groundwater underlying two swine production facilities. Appl Environ Microbiol. 67:2001;1494-1502. This study demonstrates the direct correlation of agricultural use of antibiotics and the presence and spread via groundwater of diverse antibiotic resistance genes in the bacteria of gastrointestinal origin and in the indigenous soil microbiota.
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Appl Environ Microbiol
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Chee-Sanford, J.C.1
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Mackie, R.I.5
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13
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Transmission of Escherichia coli O157:H7 from contaminated manure and irrigation water to lettuce plant tissue and its subsequent internalization
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This study provides compelling evidence that pathogenic bacteria from contaminated soil and water sources can enter roots and migrate internally throughout the edible portions of plants.
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Solomon E.B., Yaron S., Matthews K.R. Transmission of Escherichia coli O157:H7 from contaminated manure and irrigation water to lettuce plant tissue and its subsequent internalization. Appl Environ Microbiol. 68:2002;397-400. This study provides compelling evidence that pathogenic bacteria from contaminated soil and water sources can enter roots and migrate internally throughout the edible portions of plants.
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Solomon, E.B.1
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Matthews, K.R.3
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Harwood V.J., Whitlock J., Withington V. Classification of antibiotic resistance patterns of indicator bacteria by discriminant analysis: use in predicting the source of fecal contamination in subtropical waters. Appl Environ Microbiol. 66:2000;3698-3704.
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Withington, V.3
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This study provides eye-opening evidence for just how prevalent horizontal gene transfer occurs in natural environments such as the gut. The authors show that a substantial increase in tetracycline resistance among both community and clinical isolates of Bacteroides has occurred over the past few decades. The source of this resistance was the spread of a single gene by conjugative transposons. The authors also provide compelling evidence that Bacteroides may have acquired erythromycin resistance genes from other bacterial species.
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Shoemaker N.B., Vlamakis H., Hayes K., Salyers A.A. Evidence for extensive resistance gene transfer among Bacteroides spp. and among Bacteroides and other genera in the human colon. Appl Environ Microbiol. 67:2001;561-568. This study provides eye-opening evidence for just how prevalent horizontal gene transfer occurs in natural environments such as the gut. The authors show that a substantial increase in tetracycline resistance among both community and clinical isolates of Bacteroides has occurred over the past few decades. The source of this resistance was the spread of a single gene by conjugative transposons. The authors also provide compelling evidence that Bacteroides may have acquired erythromycin resistance genes from other bacterial species.
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Appl Environ Microbiol
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Shoemaker, N.B.1
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Hayes, K.3
Salyers, A.A.4
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Integration and excision of a Bacteroides conjugative transposon, CTnDOT
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Cheng Q., Paszkiet B.J., Shoemaker N.B., Gardner J.F., Salyers A.A. Integration and excision of a Bacteroides conjugative transposon, CTnDOT. J Bacteriol. 182:2000;4035-4043.
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0034892598
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Identification of genes required for excision of CTnDOT, a Bacteroides conjugative transposon
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Cheng Q., Sutanto Y., Shoemaker N.B., Gardner J.F., Salyers A.A. Identification of genes required for excision of CTnDOT, a Bacteroides conjugative transposon. Mol Microbiol. 41:2001;625-632.
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Mol Microbiol
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Cheng, Q.1
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Salyers, A.A.5
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18
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0033523872
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An outbreak of multidrug-resistant, quinolone-resistant Salmonella enterica serotype typhimurium DT104
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Molbak K., Baggesen D.L., Aarestrup F.M., Ebbesen J.M., Engberg J., Frydendahl K., Gerner-Smidt P., Petersen A.M., Wegener H.C. An outbreak of multidrug-resistant, quinolone-resistant Salmonella enterica serotype typhimurium DT104. N Engl J Med. 341:1999;1420-1425.
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Gerner-Smidt, P.7
Petersen, A.M.8
Wegener, H.C.9
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19
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0035793372
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Molecular analysis of commensal host-microbial relationships in the intestine
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This study is a groundbreaking demonstration of how new technologies can help us to understand the host response to bacterial colonization. The authors used DNA microarrays coupled with laser-capture microdissection to observe the intestinal transcriptional responses in germ-free mice to colonization with bacteria.
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Hooper L.V., Wong M.H., Thelin A., Hansson L., Falk P.G., Gordon J.I. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 291:2001;881-884. This study is a groundbreaking demonstration of how new technologies can help us to understand the host response to bacterial colonization. The authors used DNA microarrays coupled with laser-capture microdissection to observe the intestinal transcriptional responses in germ-free mice to colonization with bacteria.
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Science
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Hooper, L.V.1
Wong, M.H.2
Thelin, A.3
Hansson, L.4
Falk, P.G.5
Gordon, J.I.6
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20
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This review nicely summarizes the current picture of our understanding of the interactions between commensal microflora and the host.
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Hooper L.V., Gordon J.I. Commensal host-bacterial relationships in the gut. Science. 292:2001;1115-1119. This review nicely summarizes the current picture of our understanding of the interactions between commensal microflora and the host.
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Science
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Hooper, L.V.1
Gordon, J.I.2
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Biochemical analysis of interactions between outer membrane proteins that contribute to starch utilization by Bacteroides thetaiotaomicron
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Cho K.H., Salyers A.A. Biochemical analysis of interactions between outer membrane proteins that contribute to starch utilization by Bacteroides thetaiotaomicron. J Bacteriol. 183:2001;7224-7230.
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J Bacteriol
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Cho, K.H.1
Salyers, A.A.2
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22
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Characterization of four outer membrane proteins involved in binding starch to the cell surface of Bacteroides thetaiotaomicron
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Shipman J.A., Berleman J.E., Salyers A.A. Characterization of four outer membrane proteins involved in binding starch to the cell surface of Bacteroides thetaiotaomicron. J Bacteriol. 182:2000;5365-5372.
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Shipman, J.A.1
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Salyers, A.A.3
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23
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0035969489
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Extensive surface diversity of a commensal microorganism by multiple DNA inversions
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This study illustrates the sophistication of the mechanisms used by commensal microorganisms to colonize the gut. The authors show that Bacteroides fragilis is able to modulate its surface antigenicity by phase-regulated expression of at least eight different capsular polysaccharides.
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Krinos C.M., Coyne M.J., Weinacht K.G., Tzianabos A.O., Kasper D.L., Comstock L.E. Extensive surface diversity of a commensal microorganism by multiple DNA inversions. Nature. 414:2001;555-558. This study illustrates the sophistication of the mechanisms used by commensal microorganisms to colonize the gut. The authors show that Bacteroides fragilis is able to modulate its surface antigenicity by phase-regulated expression of at least eight different capsular polysaccharides.
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Nature
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Krinos, C.M.1
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Kasper, D.L.5
Comstock, L.E.6
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24
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0034705397
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A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria
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Macpherson A.J., Gatto D., Sainsbury E., Harriman G.R., Hengartner H., Zinkernagel R.M. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science. 288:2000;2222-2226.
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Zinkernagel, R.M.6
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25
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IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms
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Macpherson A.J., Hunziker L., McCoy K., Lamarre A. IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect. 3:2001;1021-1035.
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Macpherson, A.J.1
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Lamarre, A.4
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0033955438
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Recent developments in the immunology of inflammatory bowel disease
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This review summarizes the current status of the field of inflammatory bowel disease, current thoughts on its causes, and various strategies being explored to treat the disease.
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MacDonald T.T., Monteleone G., Pender S.L. Recent developments in the immunology of inflammatory bowel disease. Scand J Immunol. 51:2000;2-9. This review summarizes the current status of the field of inflammatory bowel disease, current thoughts on its causes, and various strategies being explored to treat the disease.
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Scand J Immunol
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MacDonald, T.T.1
Monteleone, G.2
Pender, S.L.3
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27
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Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice
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O'Mahony L., Feeney M., O'Halloran S., Murphy L., Kiely B., Fitzgibbon J., Lee G., O'Sullivan G., Shanahan F., Collins J.K. Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice. Aliment Pharmacol Ther. 15:2001;1219-1225.
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Aliment Pharmacol Ther
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O'Mahony, L.1
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Fitzgibbon, J.6
Lee, G.7
O'Sullivan, G.8
Shanahan, F.9
Collins, J.K.10
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28
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0034714188
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Treatment of murine colitis by Lactococcus lactis secreting interleukin-10
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This study establishes proof-of-principle for an exciting new approach to treat inflammatory bowel disease. The authors demonstrated the localized and effective delivery of an anti-inflammatory drug in two mouse models of colitis using probiotic bacteria genetically engineered to produce the cytokine IL-10.
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Steidler L., Hans W., Schotte L., Neirynck S., Obermeier F., Falk W., Fiers W., Remaut E. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science. 289:2000;1352-1355. This study establishes proof-of-principle for an exciting new approach to treat inflammatory bowel disease. The authors demonstrated the localized and effective delivery of an anti-inflammatory drug in two mouse models of colitis using probiotic bacteria genetically engineered to produce the cytokine IL-10.
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Science
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Steidler, L.1
Hans, W.2
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Understanding the mode of action of diphtheria toxin: A perspective on progress during the 20th century
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Collier R.J. Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century. Toxicon. 39:2001;1793-1803.
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Collier, R.J.1
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In vitro assessment of a chemically synthesized Shiga toxin receptor analog attached to chromosorb P (Synsorb Pk) as a specific absorbing agent of Shiga toxin 1 and 2
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Takeda T., Yoshino K., Adachi E., Sato Y., Yamagata K. In vitro assessment of a chemically synthesized Shiga toxin receptor analog attached to chromosorb P (Synsorb Pk) as a specific absorbing agent of Shiga toxin 1 and 2. Microbiol Immunol. 43:1999;331-337.
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A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans
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This study couples probiotics with the concept of multivalent ligand inhibitor design to neutralize protein toxins released by enteric bacteria. The authors engineered E. coli to express lipopolysaccharides on their surface that mimic the Shiga toxin receptor. Oral administration of these recombinant bacteria completely protected mice from lethal challenge with Shiga-toxin-producing E. coli.
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Paton A.W., Morona R., Paton J.C. A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans. Nat Med. 6:2000;265-270. This study couples probiotics with the concept of multivalent ligand inhibitor design to neutralize protein toxins released by enteric bacteria. The authors engineered E. coli to express lipopolysaccharides on their surface that mimic the Shiga toxin receptor. Oral administration of these recombinant bacteria completely protected mice from lethal challenge with Shiga-toxin-producing E. coli.
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Nat Med
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Paton, A.W.1
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Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands
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This study demonstrates the power of rational design to generate potent antimicrobials. The authors used the crystal structure of the B subunit pentamer of Shiga-like toxin bound to an analog of its carbohydrate receptor to design a multivalent ligand inhibitor of the toxin. This study also illustrates the importance of confirming computational predictions with experimentation. The authors discovered that the inhibitor, although quite potent, did not actually bind to the toxin in the originally intended manner predicted by molecular modeling.
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Kitov P.I., Sadowska J.M., Mulvey G., Armstrong G.D., Ling H., Pannu N.S., Read R.J., Bundle D.R. Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands. Nature. 403:2000;669-672. This study demonstrates the power of rational design to generate potent antimicrobials. The authors used the crystal structure of the B subunit pentamer of Shiga-like toxin bound to an analog of its carbohydrate receptor to design a multivalent ligand inhibitor of the toxin. This study also illustrates the importance of confirming computational predictions with experimentation. The authors discovered that the inhibitor, although quite potent, did not actually bind to the toxin in the originally intended manner predicted by molecular modeling.
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Nature
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Kitov, P.I.1
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Pannu, N.S.6
Read, R.J.7
Bundle, D.R.8
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33
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0034784582
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Designing a polyvalent inhibitor of anthrax toxin
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This study shows how weakly binding peptides identified from screening phage-display libraries could be linked together to increase their binding affinity and efficacy. Linking multiple copies of such a weak-binding peptide to a template yielded a polyvalent inhibitor that inhibited interaction between anthrax protective antigen and edema factor or lethal factor, thereby preventing anthrax toxin assembly. The inhibitor blocked toxin action in a rat model of intoxication.
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Mourez M., Kane R.S., Mogridge J., Metallo S., Deschatelets P., Sellman B.R., Whitesides G.M., Collier R.J. Designing a polyvalent inhibitor of anthrax toxin. Nat Biotechnol. 19:2001;958-961. This study shows how weakly binding peptides identified from screening phage-display libraries could be linked together to increase their binding affinity and efficacy. Linking multiple copies of such a weak-binding peptide to a template yielded a polyvalent inhibitor that inhibited interaction between anthrax protective antigen and edema factor or lethal factor, thereby preventing anthrax toxin assembly. The inhibitor blocked toxin action in a rat model of intoxication.
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Nat Biotechnol
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Mourez, M.1
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Sellman, B.R.6
Whitesides, G.M.7
Collier, R.J.8
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34
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0035957753
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Dominant-negative mutants of a toxin subunit: An approach to therapy of anthrax
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This study, along with a similar study by another group [36••], demonstrates the feasibility of using dominant-negative mutants of the oligomeric B subunit complex of a toxin as an alternative antitoxin strategy against anthrax. Using mutants of anthrax protective antigen, which still assemble into heptameric complexes on the host cell surface but do not allow translocation of the edema factor or lethal factor into the host cell, the authors show that these mutants can block toxin action in vitro and in vivo.
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Sellman B.R., Mourez M., Collier R.J. Dominant-negative mutants of a toxin subunit: an approach to therapy of anthrax. Science. 292:2001;695-697. This study, along with a similar study by another group [36••], demonstrates the feasibility of using dominant-negative mutants of the oligomeric B subunit complex of a toxin as an alternative antitoxin strategy against anthrax. Using mutants of anthrax protective antigen, which still assemble into heptameric complexes on the host cell surface but do not allow translocation of the edema factor or lethal factor into the host cell, the authors show that these mutants can block toxin action in vitro and in vivo.
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Science
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Sellman, B.R.1
Mourez, M.2
Collier, R.J.3
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35
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Point mutations in anthrax protective antigen that block translocation
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Sellman B.R., Nassi S., Collier R.J. Point mutations in anthrax protective antigen that block translocation. J Biol Chem. 276:2001;8371-8376.
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Sellman, B.R.1
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Collier, R.J.3
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36
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0035933746
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A dominant negative mutant of Bacillus anthracis protective antigen inhibits anthrax toxin action in vivo
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Singh Y., Khanna H., Chopra A.P., Mehra V. A dominant negative mutant of Bacillus anthracis protective antigen inhibits anthrax toxin action in vivo. J Biol Chem. 276:2001;22090-22094. See [34••].
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J Biol Chem
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Singh, Y.1
Khanna, H.2
Chopra, A.P.3
Mehra, V.4
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37
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0034750730
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A 12-amino-acid segment, present in Type s2 but not Type s1 Helicobacter pylori VacA proteins, abolishes cytotoxin activity and alters membrane channel formation
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McClain M.S., Cao P., Iwamoto H., Vinion-Dubiel A.D., Szabo G., Shao Z., Cover T.L. A 12-amino-acid segment, present in Type s2 but not Type s1 Helicobacter pylori VacA proteins, abolishes cytotoxin activity and alters membrane channel formation. J Bacteriol. 183:2001;6499-6508.
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J Bacteriol
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McClain, M.S.1
Cao, P.2
Iwamoto, H.3
Vinion-Dubiel, A.D.4
Szabo, G.5
Shao, Z.6
Cover, T.L.7
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38
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0033621333
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A dominant negative mutant of Helicobacter pylori vacuolating toxin (VacA) inhibits VacA-induced cell vacuolation
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This was the first demonstration of the use of a dominant-negative mutant of an oligomeric toxin as an antitoxin. The authors show that formation of mixed oligomers of wild-type and mutant Helicobacter pylori VacA proteins resulted in complete blockade of vacuolating activity.
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Vinion-Dubiel A.D., McClain M.S., Czajkowsky D.M., Iwamoto H., Ye D., Cao P., Schraw W., Blanke S.R., Shao Z., Cover T.L. A dominant negative mutant of Helicobacter pylori vacuolating toxin (VacA) inhibits VacA-induced cell vacuolation. J Biol Chem. 274:1999;37736-37742. This was the first demonstration of the use of a dominant-negative mutant of an oligomeric toxin as an antitoxin. The authors show that formation of mixed oligomers of wild-type and mutant Helicobacter pylori VacA proteins resulted in complete blockade of vacuolating activity.
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(1999)
J Biol Chem
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Vinion-Dubiel, A.D.1
McClain, M.S.2
Czajkowsky, D.M.3
Iwamoto, H.4
Ye, D.5
Cao, P.6
Schraw, W.7
Blanke, S.R.8
Shao, Z.9
Cover, T.L.10
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39
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0035829518
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Crystal structure of the anthrax lethal factor
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Pannifer A.D., Wong T.Y., Schwarzenbacher R., Renatus M., Petosa C., Bienkowska J., Lacy D.B., Collier R.J., Park S., Leppla S.H., et al. Crystal structure of the anthrax lethal factor. Nature. 414:2001;229-233.
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Nature
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Pannifer, A.D.1
Wong, T.Y.2
Schwarzenbacher, R.3
Renatus, M.4
Petosa, C.5
Bienkowska, J.6
Lacy, D.B.7
Collier, R.J.8
Park, S.9
Leppla, S.H.10
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40
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0033913887
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Differential modulation and subsequent blockade of mitogenic signaling and cell cycle progression by Pasteurella multocida toxin
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q protein, in those cells. These downstream, long-term consequences of toxin action could potentially be exploited in the design of new, alternative antitoxin treatment modalities.
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q protein, in those cells. These downstream, long-term consequences of toxin action could potentially be exploited in the design of new, alternative antitoxin treatment modalities.
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(2000)
Infect Immun
, vol.68
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Wilson, B.A.1
Aminova, L.R.2
Ponferrada, V.G.3
Ho, M.4
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44
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0035797887
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Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor
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This study illustrates how naturally occurring variants in particular host proteins may influence the inherent susceptibility or resistance of a host organism to toxin-mediated effects. The authors found that mutations in Kif1C accounted for the large differences in susceptibility of macrophages to the effects of anthrax lethal toxin and that the Kif1C-sensitive step occurs after cellular entry and processing and intracellular action (mitogen-activated protein kinase kinase 3 [MAPKK3] cleavage) of anthrax lethal toxin. Drug leads aimed at downstream cellular events may provide alternative therapeutics for countering toxin effects once exposure has occurred.
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Watters J.W., Dewar K., Lehoczky J., Boyartchuk V., Dietrich W.F. Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor. Curr Biol. 11:2001;1503-1511. This study illustrates how naturally occurring variants in particular host proteins may influence the inherent susceptibility or resistance of a host organism to toxin-mediated effects. The authors found that mutations in Kif1C accounted for the large differences in susceptibility of macrophages to the effects of anthrax lethal toxin and that the Kif1C-sensitive step occurs after cellular entry and processing and intracellular action (mitogen-activated protein kinase kinase 3 [MAPKK3] cleavage) of anthrax lethal toxin. Drug leads aimed at downstream cellular events may provide alternative therapeutics for countering toxin effects once exposure has occurred.
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(2001)
Curr Biol
, vol.11
, pp. 1503-1511
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Watters, J.W.1
Dewar, K.2
Lehoczky, J.3
Boyartchuk, V.4
Dietrich, W.F.5
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45
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0036207309
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Gene transfer between Salmonella enterica Serovar Typhimurium inside epithelial cells
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Ferguson G.C., Heinemann J.A., Kennedy M.A. Gene transfer between Salmonella enterica Serovar Typhimurium inside epithelial cells. J Bacteriol. 184:2002;2235-2242.
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J Bacteriol
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Ferguson, G.C.1
Heinemann, J.A.2
Kennedy, M.A.3
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46
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0036144233
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Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium
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Cario E., Brown D., McKee M., Lynch-Devaney K., Gerken G., Podolsky D.K. Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium. Am J Pathol. 160:2002;165-173.
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Cario, E.1
Brown, D.2
McKee, M.3
Lynch-Devaney, K.4
Gerken, G.5
Podolsky, D.K.6
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47
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0036205858
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Immunoproteomics of Helicobacter pylori infection and relation to gastric disease
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Haas G., Karaali G., Ebermayer K., Metzger W.G., Lamer S., Zimny-Arndt U., Diescher S., Goebel U.B., Vogt K., Roznowski A.B., Wiedenmann B.J., Meyer T.F., Aebischer T., Jungblut P.R. Immunoproteomics of Helicobacter pylori infection and relation to gastric disease. Proteomics. 2:2002;313-324.
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Proteomics
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Haas, G.1
Karaali, G.2
Ebermayer, K.3
Metzger, W.G.4
Lamer, S.5
Zimny-Arndt, U.6
Diescher, S.7
Goebel, U.B.8
Vogt, K.9
Roznowski, A.B.10
Wiedenmann, B.J.11
Meyer, T.F.12
Aebischer, T.13
Jungblut, P.R.14
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48
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0037012652
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q agonist Pasteurella multocida toxin to promote cardiomyocyte hypertrophy and enhance apoptosis susceptibility
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in press
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q agonist Pasteurella multocida toxin to promote cardiomyocyte hypertrophy and enhance apoptosis susceptibility. Circ Res 2002, 90: in press.
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Circ Res
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Sabri, A.1
Wilson, B.A.2
Steinberg, S.F.3
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