Mechanism of Action of and Mechanism of Reduced Susceptibility to the Novel Anti-Clostridium difficile Compound LFF571
Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commerc...
Saved in:
| Published in | Antimicrobial Agents and Chemotherapy Vol. 56; no. 8; pp. 4463 - 4465 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Washington, DC
American Society for Microbiology
01.08.2012
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Classifications
Services
AAC
Citing Articles
Google Scholar
PubMed
Related Content
Social Bookmarking
CiteULike
Delicious
Digg
Facebook
Google+
Mendeley
Reddit
StumbleUpon
Twitter
current issue
AAC
About
AAC
Subscribers
Authors
Reviewers
Advertisers
Inquiries from the Press
Permissions & Commercial Reprints
ASM Journals Public Access Policy
AAC
RSS Feeds
1752 N Street N.W. • Washington DC 20036
202.737.3600 • 202.942.9355 fax • journals@asmusa.org
Print ISSN:
0066-4804
Online ISSN:
1098-6596
Copyright © 2014
by the
American Society for Microbiology.
For an alternate route to
AAC
.asm.org, visit:
AAC
|
|---|---|
| AbstractList | Classifications
Services
AAC
Citing Articles
Google Scholar
PubMed
Related Content
Social Bookmarking
CiteULike
Delicious
Digg
Facebook
Google+
Mendeley
Reddit
StumbleUpon
Twitter
current issue
AAC
About
AAC
Subscribers
Authors
Reviewers
Advertisers
Inquiries from the Press
Permissions & Commercial Reprints
ASM Journals Public Access Policy
AAC
RSS Feeds
1752 N Street N.W. • Washington DC 20036
202.737.3600 • 202.942.9355 fax • journals@asmusa.org
Print ISSN:
0066-4804
Online ISSN:
1098-6596
Copyright © 2014
by the
American Society for Microbiology.
For an alternate route to
AAC
.asm.org, visit:
AAC
LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive bacteria. We report that the antibacterial activity of LFF571 against Clostridium difficile is due to inhibition of translation. Single-step mutants of C. difficile with reduced susceptibility to LFF571 were selected at frequencies of <4.5 × 10 −11 to 1.2 × 10 −9 . Sequencing revealed a G260E substitution in the thiopeptide-binding pocket of elongation factor Tu. Importantly, this mutation did not confer cross-resistance to clinically used antimicrobials. These results support the development of LFF571 as a treatment for C. difficile infection. LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive bacteria. We report that the antibacterial activity of LFF571 against Clostridium difficile is due to inhibition of translation. Single-step mutants of C. difficile with reduced susceptibility to LFF571 were selected at frequencies of <4.5 × 10(-11) to 1.2 × 10(-9). Sequencing revealed a G260E substitution in the thiopeptide-binding pocket of elongation factor Tu. Importantly, this mutation did not confer cross-resistance to clinically used antimicrobials. These results support the development of LFF571 as a treatment for C. difficile infection. ABSTRACT LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive bacteria. We report that the antibacterial activity of LFF571 against Clostridium difficile is due to inhibition of translation. Single-step mutants of C. difficile with reduced susceptibility to LFF571 were selected at frequencies of <4.5 × 10 −11 to 1.2 × 10 −9 . Sequencing revealed a G260E substitution in the thiopeptide-binding pocket of elongation factor Tu. Importantly, this mutation did not confer cross-resistance to clinically used antimicrobials. These results support the development of LFF571 as a treatment for C. difficile infection. LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive bacteria. We report that the antibacterial activity of LFF571 against Clostridium difficile is due to inhibition of translation. Single-step mutants of C. difficile with reduced susceptibility to LFF571 were selected at frequencies of <4.5 × 10−11 to 1.2 × 10−9. Sequencing revealed a G260E substitution in the thiopeptide-binding pocket of elongation factor Tu. Importantly, this mutation did not confer cross-resistance to clinically used antimicrobials. These results support the development of LFF571 as a treatment for C. difficile infection. |
| Author | M. J. LaMarche S. Mullin J. A. Leeds M. Sachdeva J. Dzink-Fox |
| Author_xml | – sequence: 1 givenname: J. A surname: LEEDS fullname: LEEDS, J. A organization: Novartis Institutes for Biomedical Research, Infectious Disease Area, Emeryville, California, United States – sequence: 2 givenname: M surname: SACHDEVA fullname: SACHDEVA, M organization: Novartis Institutes for Biomedical Research, Infectious Disease Area, Emeryville, California, United States – sequence: 3 givenname: S surname: MULLIN fullname: MULLIN, S organization: Novartis Institutes for Biomedical Research, Infectious Disease Area, Emeryville, California, United States – sequence: 4 givenname: J surname: DZINK-FOX fullname: DZINK-FOX, J organization: Novartis Institutes for Biomedical Research, Infectious Disease Area, Emeryville, California, United States – sequence: 5 givenname: M. J surname: LAMARCHE fullname: LAMARCHE, M. J organization: Global Discovery Chemistry, Cambridge, Massachusetts, United States |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26180163$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22644023$$D View this record in MEDLINE/PubMed |
| BookMark | eNp1kUFv1DAQhS1URLeFG2dkDkggkWI7tpNckKKoC0gLSNC7Nes4XVeJvbWdRf339bJLoQdOM6P59EZv3hk6cd4ZhF5SckEpqz-0bXdBZCl4QekTtKCkqQspGnmCFoRIWfCa8FN0FuMNybNoyDN0ypjknLBygXZfjd6As3HCfsCtTta7fQeux49WP0w_a9Pjn3PUZpvs2o423eHkcdoY_M3vzIhbl2zRjT6mYHs7T7i3w2C1HQ3u_LT1cxZdLZeios_R0wHGaF4c6zm6Wl5edZ-L1fdPX7p2VYCgVSok6fXApGwMkKaXlagNX5tG9iURZTYDJWVQsWoQVS-oKGXDBRgtJOg1IVCeo48H2e28nkyvjUsBRrUNdoJwpzxY9Xjj7EZd-50qOaOS1Vng7VEg-NvZxKQmm_2PIzjj56goYVVdclHJjL4_oDr4GIMZHs5QovZJqZyU-p1UHjP-7oBDnJi68XNw-RH_Y1_9a-NB-E-MGXhzBCBqGIcATtv4l5O0JlTuudcHbmOvN79sMCpfVwBaCalqxXlm7gGZ3rTZ |
| CODEN | AACHAX |
| CitedBy_id | crossref_primary_10_1093_jac_dkt013 crossref_primary_10_1128_AAC_04436_14 crossref_primary_10_1002_ange_201307288 crossref_primary_10_1517_14656566_2013_838218 crossref_primary_10_1128_AAC_04251_14 crossref_primary_10_1016_j_ijantimicag_2013_10_002 crossref_primary_10_1080_14787210_2016_1211931 crossref_primary_10_1128_JB_02243_14 crossref_primary_10_1002_wnan_1819 crossref_primary_10_1039_C6NP00067C crossref_primary_10_1128_AAC_00867_12 crossref_primary_10_1002_ange_201507062 crossref_primary_10_1016_j_medmal_2017_10_008 crossref_primary_10_1080_13543784_2019_1581763 crossref_primary_10_3389_fmed_2018_00096 crossref_primary_10_3390_md12010317 crossref_primary_10_2147_JEP_S242959 crossref_primary_10_1021_acs_chemrev_8b00789 crossref_primary_10_3390_biomedicines11020426 crossref_primary_10_1016_j_ejmech_2019_02_068 crossref_primary_10_1038_s41426_017_0019_4 crossref_primary_10_1002_anie_201307288 crossref_primary_10_1021_acs_jmedchem_6b00726 crossref_primary_10_1038_nrmicro2937 crossref_primary_10_1021_acs_chemrev_6b00623 crossref_primary_10_3389_fmicb_2021_616979 crossref_primary_10_1002_cmdc_201800597 crossref_primary_10_1097_MOG_0000000000000332 crossref_primary_10_1021_acs_jnatprod_2c00093 crossref_primary_10_1093_jac_dkt302 crossref_primary_10_1007_s10295_015_1691_9 crossref_primary_10_1128_AAC_06355_11 crossref_primary_10_1002_anie_201507062 crossref_primary_10_1007_s11908_020_00730_1 crossref_primary_10_1038_ja_2013_86 crossref_primary_10_1111_nyas_13958 crossref_primary_10_1039_C4NP00064A |
| Cites_doi | 10.1016/S0016-5085(09)60516-3 10.1128/AAC.06305-11 10.1111/j.1749-6632.1974.tb43276.x 10.1038/nrgastro.2010.190 10.1111/j.1469-0691.2009.03099.x 10.1086/521860 10.4161/gmic.1.4.12706 10.1093/jac/dkp041 10.1021/jm201685h 10.1006/jmbi.2000.4260 10.1128/AAC.06355-11 10.1056/NEJMoa0910812 10.1128/AAC.00582-11 10.1021/bi0525122 10.1099/13500872-141-2-371 10.7164/antibiotics.44.693 |
| ContentType | Journal Article |
| Copyright | 2015 INIST-CNRS Copyright © 2012, American Society for Microbiology. All Rights Reserved. Copyright © 2012, American Society for Microbiology. All Rights Reserved. 2012 American Society for Microbiology |
| Copyright_xml | – notice: 2015 INIST-CNRS – notice: Copyright © 2012, American Society for Microbiology. All Rights Reserved. – notice: Copyright © 2012, American Society for Microbiology. All Rights Reserved. 2012 American Society for Microbiology |
| DBID | IQODW CGR CUY CVF ECM EIF NPM AAYXX CITATION 7X8 5PM |
| DOI | 10.1128/AAC.06354-11 |
| DatabaseName | Pascal-Francis Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef MEDLINE - Academic |
| DatabaseTitleList | MEDLINE CrossRef MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Pharmacy, Therapeutics, & Pharmacology Biology |
| EISSN | 1098-6596 |
| EndPage | 4465 |
| ExternalDocumentID | 10_1128_AAC_06354_11 06354-11 22644023 26180163 aac_56_8_4463 |
| Genre | Journal Article |
| GroupedDBID | --- .55 .GJ 08R 0R~ 23M 2WC 39C 3O- 4.4 53G 5GY 5RE 5VS 6J9 AAPBV AAUGY ACGFO ADBBV AENEX AFMIJ AGNAY AI. ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BTFSW C1A CS3 DIK E3Z EBS EJD F5P FRP GX1 H13 HH5 HYE HZ~ H~9 IQODW J5H K-O KQ8 L7B LSO MVM NEJ O9- OK1 P2P RHF RHI RNS RPM RSF TR2 UHB VH1 W2D W8F WH7 WHG WOQ X7M X7N XOL Y6R ZA5 ZGI ZXP ~A~ AGVNZ CGR CUY CVF ECM EIF NPM - 0R 55 ABFLS ADACO BXI HZ AAYXX CITATION 7X8 5PM |
| ID | FETCH-LOGICAL-a517t-60dcf2669ea09d6758e4be96d3053065a312a727f57d51536945aec56acb00a3 |
| IEDL.DBID | RPM |
| ISSN | 0066-4804 |
| IngestDate | Tue Sep 17 21:08:20 EDT 2024 Fri Oct 25 01:31:37 EDT 2024 Thu Sep 12 17:51:31 EDT 2024 Tue Dec 28 13:59:23 EST 2021 Sat Nov 02 12:29:19 EDT 2024 Sun Oct 22 16:08:17 EDT 2023 Wed May 18 15:26:55 EDT 2016 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 8 |
| Keywords | Sensitivity Clostridiaceae Clostridium difficile Clostridiales Diarrhea Bacteria Digestive diseases Intestinal disease Mechanism of action |
| Language | English |
| License | CC BY 4.0 |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-a517t-60dcf2669ea09d6758e4be96d3053065a312a727f57d51536945aec56acb00a3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://aac.asm.org/content/aac/56/8/4463.full.pdf |
| PMID | 22644023 |
| PQID | 1027834576 |
| PQPubID | 23479 |
| PageCount | 3 |
| ParticipantIDs | pascalfrancis_primary_26180163 pubmedcentral_primary_oai_pubmedcentral_nih_gov_3421628 pubmed_primary_22644023 proquest_miscellaneous_1027834576 asm2_journals_10_1128_AAC_06354_11 crossref_primary_10_1128_AAC_06354_11 highwire_asm_aac_56_8_4463 |
| PublicationCentury | 2000 |
| PublicationDate | 2012-08-01 |
| PublicationDateYYYYMMDD | 2012-08-01 |
| PublicationDate_xml | – month: 08 year: 2012 text: 2012-08-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | Washington, DC |
| PublicationPlace_xml | – name: Washington, DC – name: United States – name: 1752 N St., N.W., Washington, DC |
| PublicationTitle | Antimicrobial Agents and Chemotherapy |
| PublicationTitleAbbrev | Antimicrob Agents Chemother |
| PublicationTitleAlternate | Antimicrob Agents Chemother |
| PublicationYear | 2012 |
| Publisher | American Society for Microbiology |
| Publisher_xml | – name: American Society for Microbiology |
| References | Critchley, IA (B7) 2009; 63 B10 B12 Zuurmond, AM (B23) 2000; 304 Louie, TJ (B16) 2011; 364 Citron, DM, Tyrrell, KL, Merriam, CV, Goldstein, EJ (B4) 2012; 56 LaMarche, MJ (B14) 2012; 55 Leeds, JA (B15) 2011; 55 Miller, M, Mullane, KM, Weiss, K (B17) 2009; 136 Ananthakrishnan, AN (B1) 2011; 8 B3 (B6) 2011 Karasawa, T, Ikoma, S, Yamakawa, K, Nakamura, S (B13) 1995; 141 Selva, E (B21) 1991; 44 (B5) 2010 B8 B9 Perkins, HR, Nieto, M (B20) 1974; 235 Trzasko, A, Leeds, JA, Praestgaard, J, LaMarche, MJ, McKenney, D (B21a) 2012; 56 Nelson, RL (B18) 2007; 2007 Gerding, DN, Muto, CA, Owens, RC (B11) 2008; 46 Viswanathan, VK, Mallozzi, MJ, Vedantam, G (B22) 2010; 1 Bauer, MP, Kuijper, EJ, van Dissel, JT (B2) 2009; 15 Parmeggiani, A (B19) 2006; 45 e_1_3_2_15_2 e_1_3_2_8_2 Deng G (e_1_3_2_10_2) 2011 e_1_3_2_16_2 e_1_3_2_17_2 Clinical and Laboratory Standards Institute (e_1_3_2_6_2) 2010 e_1_3_2_18_2 Clinical and Laboratory Standards Institute (e_1_3_2_7_2) 2011 e_1_3_2_21_2 e_1_3_2_5_2 e_1_3_2_4_2 e_1_3_2_12_2 e_1_3_2_23_2 e_1_3_2_3_2 Dzink-Fox J (e_1_3_2_11_2) 2011 e_1_3_2_24_2 e_1_3_2_2_2 e_1_3_2_14_2 e_1_3_2_25_2 Nelson RL (e_1_3_2_19_2) 2007; 2007 Crook D (e_1_3_2_9_2) 2010 Hecht D (e_1_3_2_13_2) 2012 Selva E (e_1_3_2_22_2) 1991; 44 Parmeggiani A (e_1_3_2_20_2) 2006; 45 |
| References_xml | – volume: 55 start-page: 5277 year: 2011 end-page: 5283 ident: B15 article-title: In vitro and in vivo activities of novel, semisynthetic thiopeptide inhibitors of bacterial elongation factor Tu publication-title: Antimicrob. Agents Chemother. contributor: fullname: Leeds, JA – ident: B12 article-title: Hecht D Osmolski J Gerding D . 2012 . Activity of LFF571 against 103 clinical isolates of C. difficile , abstr P1440 . Abstr. 22nd Eur. Society of Clinical Microbiology and Infectious Diseases , London, United Kingdom . – volume: 235 start-page: 348 year: 1974 end-page: 363 ident: B20 article-title: The chemical basis for the action of the vancomycin group of antibiotics publication-title: Ann. N. Y. Acad. Sci. contributor: fullname: Nieto, M – volume: 141 start-page: 371 year: 1995 end-page: 375 ident: B13 article-title: A defined growth medium for Clostridium difficile publication-title: Microbiology contributor: fullname: Nakamura, S – year: 2010 ident: B5 article-title: Methods for antimicrobial susceptibility testing of anaerobic bacteria, 7th ed publication-title: Approved standard M11-7. ;Clinical and Laboratory Standards Institute ;Wayne, PA – ident: B8 article-title: Crook D . 2010 . Randomized clinical trial in Clostridium difficile infection confirms equivalent cure rate and lower recurrence rate of fidaxomicin vs vancomycin, abstr P-LB2401 . Abstr. 20th Eur. Congr. Clin. Microbiol. Infect. Dis. , Vienna, Austria . – volume: 304 start-page: 995 year: 2000 end-page: 1005 ident: B23 article-title: GE2270A-resistant mutations in elongation factor Tu allow productive aminoacyl-tRNA binding to EF-Tu.GTP.GE2270A complexes publication-title: J. Mol. Biol. contributor: fullname: Zuurmond, AM – volume: 364 start-page: 422 year: 2011 end-page: 431 ident: B16 article-title: Fidaxomicin versus vancomycin for Clostridium difficile infection publication-title: N. Engl. J. Med. contributor: fullname: Louie, TJ – year: 2011 ident: B6 article-title: Performance standards for antimicrobial susceptibility testing publication-title: Approved standard M100-S21. Twenty-first informational supplement. ;Clinical and Laboratory Standards Institute ;Wayne, PA – volume: 56 start-page: 4459 year: 2012 end-page: 4462 ident: B21a article-title: Efficacy of LFF571 in a hamster model of Clostridium difficile infection publication-title: Antimicrob. Agents Chemother. contributor: fullname: McKenney, D – ident: B9 article-title: Deng G . 2011 . Investigation of mode of binding of elongation factor tu inhibitor LFF571, abstr F1-1859 . Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother. , Chicago, IL . – ident: B10 article-title: Dzink-Fox J . 2011 Antimicrobial activity of the novel elongation factor Tu Inhibitor, LFF571, abstr F1-1346 . Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother. , Chicago, IL . – volume: 1 start-page: 234 year: 2010 end-page: 242 ident: B22 article-title: Clostridium difficile infection: an overview of the disease and its pathogenesis, epidemiology and interventions publication-title: Gut Microbes contributor: fullname: Vedantam, G – volume: 63 start-page: 954 year: 2009 end-page: 963 ident: B7 article-title: Spectrum of activity and mode of action of REP3123, a new antibiotic to treat Clostridium difficile infections publication-title: J. Antimicrob. Chemother. contributor: fullname: Critchley, IA – ident: B3 article-title: Reference deleted . – volume: 136 start-page: A-115 year: 2009 ident: B17 article-title: OPT-80 versus vancomycin in Clostridium difficile infection: results of randomized clinical trial publication-title: Gastroenterology doi: 10.1016/S0016-5085(09)60516-3 contributor: fullname: Weiss, K – volume: 8 start-page: 17 year: 2011 end-page: 26 ident: B1 article-title: Clostridium difficile infection: epidemiology, risk factors and management publication-title: Nat. Rev. Gastroenterol. Hepatol. contributor: fullname: Ananthakrishnan, AN – volume: 56 start-page: 2493 year: 2012 end-page: 2503 ident: B4 article-title: Comparative in vitro activities of LFF571 against Clostridium difficile and 630 other intestinal strains of aerobic and anaerobic bacteria publication-title: Antimicrob. Agents Chemother. contributor: fullname: Goldstein, EJ – volume: 55 start-page: 2376 year: 2012 end-page: 2387 ident: B14 article-title: Discovery of LFF571: an investigational agent for Clostridium difficile infection publication-title: J. Med. Chem. contributor: fullname: LaMarche, MJ – volume: 45 start-page: 6846 year: 2006 end-page: 6857 ident: B19 article-title: Structural basis of the action of pulvomycin and GE2270 A on elongation factor Tu publication-title: Biochemistry contributor: fullname: Parmeggiani, A – volume: 44 start-page: 693 year: 1991 end-page: 701 ident: B21 article-title: Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. I. Isolation and characterization publication-title: J. Antibiot. (Tokyo) contributor: fullname: Selva, E – volume: 15 start-page: 1067 year: 2009 end-page: 1079 ident: B2 article-title: European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI) publication-title: Clin. Microbiol. Infect. contributor: fullname: van Dissel, JT – volume: 46 start-page: S32 year: 2008 end-page: S42 ident: B11 article-title: Treatment of Clostridium difficile infection publication-title: Clin. Infect. Dis. contributor: fullname: Owens, RC – volume: 2007 start-page: CD004610 year: 2007 ident: B18 article-title: Antibiotic treatment for Clostridium difficile-associated diarrhea in adults publication-title: Cochrane Database Syst. Rev. contributor: fullname: Nelson, RL – ident: e_1_3_2_5_2 doi: 10.1128/AAC.06305-11 – volume: 2007 start-page: CD004610 year: 2007 ident: e_1_3_2_19_2 article-title: Antibiotic treatment for Clostridium difficile-associated diarrhea in adults publication-title: Cochrane Database Syst. Rev. contributor: fullname: Nelson RL – volume-title: Approved standard M11-7. year: 2010 ident: e_1_3_2_6_2 contributor: fullname: Clinical and Laboratory Standards Institute – ident: e_1_3_2_21_2 doi: 10.1111/j.1749-6632.1974.tb43276.x – ident: e_1_3_2_2_2 doi: 10.1038/nrgastro.2010.190 – ident: e_1_3_2_3_2 doi: 10.1111/j.1469-0691.2009.03099.x – ident: e_1_3_2_12_2 doi: 10.1086/521860 – ident: e_1_3_2_24_2 doi: 10.4161/gmic.1.4.12706 – ident: e_1_3_2_8_2 doi: 10.1093/jac/dkp041 – ident: e_1_3_2_15_2 doi: 10.1021/jm201685h – volume-title: Abstr. 20th Eur. Congr. Clin. Microbiol. Infect. Dis. year: 2010 ident: e_1_3_2_9_2 contributor: fullname: Crook D – volume-title: Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother. year: 2011 ident: e_1_3_2_11_2 contributor: fullname: Dzink-Fox J – volume-title: Abstr. 22nd Eur. Society of Clinical Microbiology and Infectious Diseases year: 2012 ident: e_1_3_2_13_2 contributor: fullname: Hecht D – ident: e_1_3_2_25_2 doi: 10.1006/jmbi.2000.4260 – volume-title: Approved standard M100-S21. Twenty-first informational supplement. year: 2011 ident: e_1_3_2_7_2 contributor: fullname: Clinical and Laboratory Standards Institute – ident: e_1_3_2_23_2 doi: 10.1128/AAC.06355-11 – ident: e_1_3_2_4_2 – volume-title: Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother. year: 2011 ident: e_1_3_2_10_2 contributor: fullname: Deng G – ident: e_1_3_2_17_2 doi: 10.1056/NEJMoa0910812 – ident: e_1_3_2_16_2 doi: 10.1128/AAC.00582-11 – volume: 45 start-page: 6846 year: 2006 ident: e_1_3_2_20_2 article-title: Structural basis of the action of pulvomycin and GE2270 A on elongation factor Tu publication-title: Biochemistry doi: 10.1021/bi0525122 contributor: fullname: Parmeggiani A – ident: e_1_3_2_14_2 doi: 10.1099/13500872-141-2-371 – volume: 44 start-page: 693 year: 1991 ident: e_1_3_2_22_2 article-title: Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. I. Isolation and characterization publication-title: J. Antibiot. (Tokyo) doi: 10.7164/antibiotics.44.693 contributor: fullname: Selva E – ident: e_1_3_2_18_2 doi: 10.1016/S0016-5085(09)60516-3 |
| SSID | ssj0006590 |
| Score | 2.298926 |
| Snippet | Classifications
Services
AAC
Citing Articles
Google Scholar
PubMed
Related Content
Social Bookmarking
CiteULike
Delicious
Digg
Facebook
Google+
Mendeley
Reddit... LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive bacteria. We report that the antibacterial activity of LFF571 against... ABSTRACT LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive bacteria. We report that the antibacterial activity of LFF571... |
| SourceID | pubmedcentral proquest crossref asm2 pubmed pascalfrancis highwire |
| SourceType | Open Access Repository Aggregation Database Index Database Publisher |
| StartPage | 4463 |
| SubjectTerms | Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Binding Sites - genetics Biological and medical sciences Clostridioides difficile - drug effects Clostridioides difficile - genetics Clostridium difficile Drug Resistance, Bacterial - genetics Enterocolitis, Pseudomembranous - drug therapy Enterocolitis, Pseudomembranous - microbiology Experimental Therapeutics Gastroenterology. Liver. Pancreas. Abdomen Humans Medical sciences Microbial Sensitivity Tests Other diseases. Semiology Peptide Chain Elongation, Translational Peptide Chain Elongation, Translational - drug effects Peptide Elongation Factor Tu Peptide Elongation Factor Tu - genetics Pharmacology. Drug treatments Protein Structure, Tertiary Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Thiazoles Thiazoles - pharmacology |
| Title | Mechanism of Action of and Mechanism of Reduced Susceptibility to the Novel Anti-Clostridium difficile Compound LFF571 |
| URI | http://aac.asm.org/content/56/8/4463.abstract https://www.ncbi.nlm.nih.gov/pubmed/22644023 https://journals.asm.org/doi/10.1128/AAC.06354-11 https://search.proquest.com/docview/1027834576 https://pubmed.ncbi.nlm.nih.gov/PMC3421628 |
| Volume | 56 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb5swFD5qK23ay9RlN9ot8qatTyUJYBt4jKJF3SVVtGVS3yyDjYYUoBqkUv79jg00Y9pe9gbCICfnDt85H8C7TPPYUD-6URYwF5UidWPOEncW-izhmnlJZqd9XvOr7_TTDbs5Atb3wljQfprkk3JbTMr8h8VW3hbptMeJTderRUB9j_vR9BiOUUH7Er1zv5y1L1Ywlro0mtEe7Y7r5_PFBEMyo65nGGJMDymWTwF6Y1kX_jAy9dOCDVhS1vh_ZS3Rxd8y0T8Blb9FqOUpPO5SSzJvf8ITONLlCB60ZJP7ETxcdZ_RR3CxbgdW7y_J5tB_VV-SC7I-jLLeP4W7lTadwXldkCojc9sDYY5kqcjg0lczAVYr8m1XW5yMhdzuSVMRTDDJdXWncWNlk7uLbWWYQlS-K4ghZ8EdbTUxXsnwO5EvyyULvWewWX7YLK7cjqnBlcwLG5fPVJphqI-1nMXK1CCaJjrmCr2JoaaXgedLzJQyFipMoAIeUyZ1yrhM0exl8BxOyqrUL4EwzQP0KZmXppyqLI7QRfg61pTqWCmaOPDWyEp0llYLW8T4kUDZCitbPHXgfS9JcdsO7fjHurNezAKfKqRMBeMiElgjBw6MB4K_fxLWnBjWzYI3vSYItEnzoUWWutqZPVn-EizlHHjRasbh7k7pHAgHOnO_wMz7Hl5BM7Bzvzu1P_vvO8_hEeZ7fotffAUnzc-dfo05VZOMsZr4-HlsLekX8zodtg |
| link.rule.ids | 230,315,730,783,787,888,27936,27937,53804,53806 |
| linkProvider | National Library of Medicine |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nj9MwEB0ti_i48FEW6AKLQbCnddoktpscq4qqQFtVUNDeLCdxRESbrEi6Uvn1jJ1kS1dwgFsi25EdPY9nkjfzAN6kWoRG-pEGqc8pgiKmoeAR7Q88HgnN3Si11T7nYvKFfTjn5wfA21wYS9qPo8zJV2snz75ZbuXFOu61PLHeYjbymecKL-jdgJu4X_usDdIbAyx4_WkFT1PKsLnlu-OI4XDk4KHMGXWNRozJIsUAykd7rMq1t382tfWCDV1SlfjG0lrq4k--6HVK5W9n1Pg-fG1XV1NTvjubKnLin9cKP_7z8h_AvcZrJcO6-SEc6LwDt2ody20Hbs-aP_QdOF3UtbC3Z2S5S-0qz8gpWeyqZG8fweVMm6TjrFyTIiVDm15hrlSekL2mT6a4rE7I501pKTiWzbslVUHQdyXz4lLjxPIqo6NVYURIkmyzJkb3BWe00sQYPCMdRabjMR-4R7Acv1uOJrQRgaCKu4OKin4Sp-hFhFr1w8SEN5pFOhQJGiqjeq9811PohKV8kKBv5ouQcaVjLlSMFkX5j-EwL3L9FAjXwkdzlbpxLFiShgFaH0-HmjEdJgmLuvDagEA2m7iUNj7yAomgkRY0eNuFty1E5EVdD-Qv_Y5b_Eh8qlQqllzIQGL47XfhZA9RV0_CcBY9BtPhVQsxidvd_MNRuS42Zk5WGgWjxC48qSG3G92guQuDPTBedTClxPdbEGK2pHgDqeP_HvkS7kyWs6mcvp9_fAZ30a30aprkczisfmz0C3TdqujEbtRfE24-rQ |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1db9MwFL2CISZe-ChfGTAMgj0tbZPYbvJYFaoBa1VBkSZeLCd2tGpNUpF0Uvn1XDvJuk7wsrdEsSMnOr4-Nzm-B-BDqnlkrB_dMA2Yi6BI3Iiz2O0PfBZzzbw4tdU-p_zkJ_16xs6uWX1Z0X4SL7r5Muvmi3OrrVxlSa_VifVmk1FAfY_7YW-l0t5duIdzts_bRL0JwpzVn1dwRXVp2Ket5h17DYejLi7MjLqe8YkxO0kxiQowJssy83fXp7ZmsJFMyhLfWlrbXfyLj96UVV5bp8aP4Ff7hLU85aK7ruJu8udG8cdbvYLH8LBhr2RYN3kCd3Tegfu1n-WmA_uT5k99B45mdU3szTGZb7d4lcfkiMy21bI3T-Fyos3m40WZkSIlQ7vNwhzJXJGdS99NkVmtyI91aaU4VtW7IVVBkMOSaXGpcWB5tXBHy8KYkajFOiPG_wVHtNTEBD5jIUVOx2M28J7BfPx5PjpxGzMIVzJvULm8r5IU2USkZT9SJs3RNNYRVxiwMO1hMvB8iWQsZQOFHC3gEWVSJ4zLBCOLDJ7DXl7k-iUQpnmAYSv1koRTlUYhRiFfR5pSHSlFYwfeGyCIZjKXwuZJfigQOMICB08d-NjCRKzquiD_aXfQYkjgXYWUiWBchALT8MCBwx1UXd0J01pkDqbBuxZmAqe9-Zcjc12szZisRQpmiw68qGG37d0g2oHBDiCvGpiS4rtXEGa2tHgDq4Nb93wL-7NPY3H6ZfrtFTxAdunXasnXsFf9Xus3yOCq-NDO1b8XBUEt |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mechanism+of+Action+of+and+Mechanism+of+Reduced+Susceptibility+to+the+Novel+Anti-Clostridium+difficile+Compound+LFF571&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.au=Leeds%2C+J.+A&rft.au=Sachdeva%2C+M&rft.au=Mullin%2C+S&rft.au=Dzink-Fox%2C+J&rft.date=2012-08-01&rft.pub=American+Society+for+Microbiology&rft.issn=0066-4804&rft.eissn=1098-6596&rft.volume=56&rft.issue=8&rft.spage=4463&rft.epage=4465&rft_id=info:doi/10.1128%2FAAC.06354-11&rft.externalDocID=06354-11 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0066-4804&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0066-4804&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0066-4804&client=summon |