Repurposing ethyl bromopyruvate as a broad-spectrum antibacterial
Abstract Background The emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and ESKAPE pathogens. In comparison with conventional drug discovery, drug repurposing offers an effective yet rapid approach to identifying novel...
Saved in:
Published in | Journal of antimicrobial chemotherapy Vol. 74; no. 4; pp. 912 - 920 |
---|---|
Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
01.04.2019
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Abstract
Background
The emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and ESKAPE pathogens. In comparison with conventional drug discovery, drug repurposing offers an effective yet rapid approach to identifying novel antibiotics.
Methods
Ethyl bromopyruvate was evaluated for its ability to inhibit M. tuberculosis and ESKAPE pathogens using growth inhibition assays. The selectivity index of ethyl bromopyruvate was determined, followed by time–kill kinetics against M. tuberculosis and Staphylococcus aureus. We first tested its ability to synergize with approved drugs and then tested its ability to decimate bacterial biofilm. Intracellular killing of M. tuberculosis was determined and in vivo potential was determined in a neutropenic murine model of S. aureus infection.
Results
We identified ethyl bromopyruvate as an equipotent broad-spectrum antibacterial agent targeting drug-susceptible and -resistant M. tuberculosis and ESKAPE pathogens. Ethyl bromopyruvate exhibited concentration-dependent bactericidal activity. In M. tuberculosis, ethyl bromopyruvate inhibited GAPDH with a concomitant reduction in ATP levels and transferrin-mediated iron uptake. Apart from GAPDH, this compound inhibited pyruvate kinase, isocitrate lyase and malate synthase to varying extents. Ethyl bromopyruvate did not negatively interact with any drug and significantly reduced biofilm at a 64-fold lower concentration than vancomycin. When tested in an S. aureus neutropenic thigh infection model, ethyl bromopyruvate exhibited efficacy equal to that of vancomycin in reducing bacterial counts in thigh, and at 1/25th of the dosage.
Conclusions
Ethyl bromopyruvate exhibits all the characteristics required to be positioned as a potential broad-spectrum antibacterial agent. |
---|---|
AbstractList | The emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and ESKAPE pathogens. In comparison with conventional drug discovery, drug repurposing offers an effective yet rapid approach to identifying novel antibiotics.BACKGROUNDThe emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and ESKAPE pathogens. In comparison with conventional drug discovery, drug repurposing offers an effective yet rapid approach to identifying novel antibiotics.Ethyl bromopyruvate was evaluated for its ability to inhibit M. tuberculosis and ESKAPE pathogens using growth inhibition assays. The selectivity index of ethyl bromopyruvate was determined, followed by time-kill kinetics against M. tuberculosis and Staphylococcus aureus. We first tested its ability to synergize with approved drugs and then tested its ability to decimate bacterial biofilm. Intracellular killing of M. tuberculosis was determined and in vivo potential was determined in a neutropenic murine model of S. aureus infection.METHODSEthyl bromopyruvate was evaluated for its ability to inhibit M. tuberculosis and ESKAPE pathogens using growth inhibition assays. The selectivity index of ethyl bromopyruvate was determined, followed by time-kill kinetics against M. tuberculosis and Staphylococcus aureus. We first tested its ability to synergize with approved drugs and then tested its ability to decimate bacterial biofilm. Intracellular killing of M. tuberculosis was determined and in vivo potential was determined in a neutropenic murine model of S. aureus infection.We identified ethyl bromopyruvate as an equipotent broad-spectrum antibacterial agent targeting drug-susceptible and -resistant M. tuberculosis and ESKAPE pathogens. Ethyl bromopyruvate exhibited concentration-dependent bactericidal activity. In M. tuberculosis, ethyl bromopyruvate inhibited GAPDH with a concomitant reduction in ATP levels and transferrin-mediated iron uptake. Apart from GAPDH, this compound inhibited pyruvate kinase, isocitrate lyase and malate synthase to varying extents. Ethyl bromopyruvate did not negatively interact with any drug and significantly reduced biofilm at a 64-fold lower concentration than vancomycin. When tested in an S. aureus neutropenic thigh infection model, ethyl bromopyruvate exhibited efficacy equal to that of vancomycin in reducing bacterial counts in thigh, and at 1/25th of the dosage.RESULTSWe identified ethyl bromopyruvate as an equipotent broad-spectrum antibacterial agent targeting drug-susceptible and -resistant M. tuberculosis and ESKAPE pathogens. Ethyl bromopyruvate exhibited concentration-dependent bactericidal activity. In M. tuberculosis, ethyl bromopyruvate inhibited GAPDH with a concomitant reduction in ATP levels and transferrin-mediated iron uptake. Apart from GAPDH, this compound inhibited pyruvate kinase, isocitrate lyase and malate synthase to varying extents. Ethyl bromopyruvate did not negatively interact with any drug and significantly reduced biofilm at a 64-fold lower concentration than vancomycin. When tested in an S. aureus neutropenic thigh infection model, ethyl bromopyruvate exhibited efficacy equal to that of vancomycin in reducing bacterial counts in thigh, and at 1/25th of the dosage.Ethyl bromopyruvate exhibits all the characteristics required to be positioned as a potential broad-spectrum antibacterial agent.CONCLUSIONSEthyl bromopyruvate exhibits all the characteristics required to be positioned as a potential broad-spectrum antibacterial agent. The emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and ESKAPE pathogens. In comparison with conventional drug discovery, drug repurposing offers an effective yet rapid approach to identifying novel antibiotics. Ethyl bromopyruvate was evaluated for its ability to inhibit M. tuberculosis and ESKAPE pathogens using growth inhibition assays. The selectivity index of ethyl bromopyruvate was determined, followed by time-kill kinetics against M. tuberculosis and Staphylococcus aureus. We first tested its ability to synergize with approved drugs and then tested its ability to decimate bacterial biofilm. Intracellular killing of M. tuberculosis was determined and in vivo potential was determined in a neutropenic murine model of S. aureus infection. We identified ethyl bromopyruvate as an equipotent broad-spectrum antibacterial agent targeting drug-susceptible and -resistant M. tuberculosis and ESKAPE pathogens. Ethyl bromopyruvate exhibited concentration-dependent bactericidal activity. In M. tuberculosis, ethyl bromopyruvate inhibited GAPDH with a concomitant reduction in ATP levels and transferrin-mediated iron uptake. Apart from GAPDH, this compound inhibited pyruvate kinase, isocitrate lyase and malate synthase to varying extents. Ethyl bromopyruvate did not negatively interact with any drug and significantly reduced biofilm at a 64-fold lower concentration than vancomycin. When tested in an S. aureus neutropenic thigh infection model, ethyl bromopyruvate exhibited efficacy equal to that of vancomycin in reducing bacterial counts in thigh, and at 1/25th of the dosage. Ethyl bromopyruvate exhibits all the characteristics required to be positioned as a potential broad-spectrum antibacterial agent. Abstract Background The emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and ESKAPE pathogens. In comparison with conventional drug discovery, drug repurposing offers an effective yet rapid approach to identifying novel antibiotics. Methods Ethyl bromopyruvate was evaluated for its ability to inhibit M. tuberculosis and ESKAPE pathogens using growth inhibition assays. The selectivity index of ethyl bromopyruvate was determined, followed by time–kill kinetics against M. tuberculosis and Staphylococcus aureus. We first tested its ability to synergize with approved drugs and then tested its ability to decimate bacterial biofilm. Intracellular killing of M. tuberculosis was determined and in vivo potential was determined in a neutropenic murine model of S. aureus infection. Results We identified ethyl bromopyruvate as an equipotent broad-spectrum antibacterial agent targeting drug-susceptible and -resistant M. tuberculosis and ESKAPE pathogens. Ethyl bromopyruvate exhibited concentration-dependent bactericidal activity. In M. tuberculosis, ethyl bromopyruvate inhibited GAPDH with a concomitant reduction in ATP levels and transferrin-mediated iron uptake. Apart from GAPDH, this compound inhibited pyruvate kinase, isocitrate lyase and malate synthase to varying extents. Ethyl bromopyruvate did not negatively interact with any drug and significantly reduced biofilm at a 64-fold lower concentration than vancomycin. When tested in an S. aureus neutropenic thigh infection model, ethyl bromopyruvate exhibited efficacy equal to that of vancomycin in reducing bacterial counts in thigh, and at 1/25th of the dosage. Conclusions Ethyl bromopyruvate exhibits all the characteristics required to be positioned as a potential broad-spectrum antibacterial agent. |
Author | Singh, Alok Kumar Gani, Zahid Chopra, Sidharth Thakare, Ritesh Raje, Chaaya Iyengar Boradia, Vishant Mahendra Das, Swetarka Kumar, Ajay Patidar, Anil Raje, Manoj Dasgupta, Arunava |
AuthorAffiliation | 2 Division of Microbiology, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, Uttar Pradesh, India 1 Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Phase X, Sector 67, SAS Nagar, Punjab, India 3 Council of Scientific and Industrial Research-Institute of Microbial Technology (CSIR-IMTECH), Sector 39A, Chandigarh, India |
AuthorAffiliation_xml | – name: 1 Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Phase X, Sector 67, SAS Nagar, Punjab, India – name: 3 Council of Scientific and Industrial Research-Institute of Microbial Technology (CSIR-IMTECH), Sector 39A, Chandigarh, India – name: 2 Division of Microbiology, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, Uttar Pradesh, India |
Author_xml | – sequence: 1 givenname: Ajay surname: Kumar fullname: Kumar, Ajay organization: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Phase X, Sector 67, SAS Nagar, Punjab, India – sequence: 2 givenname: Vishant Mahendra surname: Boradia fullname: Boradia, Vishant Mahendra organization: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Phase X, Sector 67, SAS Nagar, Punjab, India – sequence: 3 givenname: Ritesh surname: Thakare fullname: Thakare, Ritesh organization: Division of Microbiology, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, Uttar Pradesh, India – sequence: 4 givenname: Alok Kumar surname: Singh fullname: Singh, Alok Kumar organization: Division of Microbiology, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, Uttar Pradesh, India – sequence: 5 givenname: Zahid surname: Gani fullname: Gani, Zahid organization: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Phase X, Sector 67, SAS Nagar, Punjab, India – sequence: 6 givenname: Swetarka surname: Das fullname: Das, Swetarka organization: Division of Microbiology, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, Uttar Pradesh, India – sequence: 7 givenname: Anil surname: Patidar fullname: Patidar, Anil organization: Council of Scientific and Industrial Research-Institute of Microbial Technology (CSIR-IMTECH), Sector 39A, Chandigarh, India – sequence: 8 givenname: Arunava surname: Dasgupta fullname: Dasgupta, Arunava organization: Division of Microbiology, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, Uttar Pradesh, India – sequence: 9 givenname: Sidharth surname: Chopra fullname: Chopra, Sidharth organization: Division of Microbiology, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, Uttar Pradesh, India – sequence: 10 givenname: Manoj surname: Raje fullname: Raje, Manoj organization: Council of Scientific and Industrial Research-Institute of Microbial Technology (CSIR-IMTECH), Sector 39A, Chandigarh, India – sequence: 11 givenname: Chaaya Iyengar surname: Raje fullname: Raje, Chaaya Iyengar email: chaaya@niper.ac.in organization: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Phase X, Sector 67, SAS Nagar, Punjab, India |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30689890$$D View this record in MEDLINE/PubMed |
BookMark | eNp9kE1LxDAQhoMo7vpx8QdIL4II1cmmSdOLsIhfsCCInsM0TbRr29SkXei_t8uuohdPAzPPPDO8B2S3cY0h5ITCJYWMXS1RXxUfA-d8h0xpIiCeQUZ3yRQY8DhNOJuQgxCWACC4kPtkwkDITGYwJfNn0_a-daFs3iLTvQ9VlHtXu3bw_Qo7E2GIcN3CIg6t0Z3v6wibrsxRd8aXWB2RPYtVMMfbekhe725fbh7ixdP94818EesEZBdjmgsLUBQSCpFnMoHCaitms7EjwSaJTG1hEQ1DYQ0iQ2a44JqnlI0bnB2S64237fPaFNo0ncdKtb6s0Q_KYan-TpryXb25lRIJzQSVo-B8K_DuszehU3UZtKkqbIzrg5rRNEsoY4KO6MUG1d6F4I39OUNBrTNXY-Zqk_kIn_5-7Af9DnkEzjaA69v_RF9sVo7m |
CitedBy_id | crossref_primary_10_3389_fphar_2024_1397602 crossref_primary_10_1093_jac_dkae051 crossref_primary_10_1016_j_micpath_2023_105992 crossref_primary_10_3390_antibiotics11060816 crossref_primary_10_1002_advs_202100681 crossref_primary_10_1007_s11095_020_02849_1 crossref_primary_10_1002_pat_5660 crossref_primary_10_3389_fmicb_2022_1029098 crossref_primary_10_3390_ijms21249507 crossref_primary_10_3390_antibiotics9100658 |
Cites_doi | 10.1038/77964 10.1074/jbc.M209248200 10.1007/s10863-012-9419-2 10.1016/S0021-9258(18)50153-8 10.7150/ijbs.7.376 10.1038/srep18176 10.1128/IAI.67.3.1086-1092.1999 10.3389/fmicb.2015.00282 10.1002/0471141755.ph13a08s50 10.1128/mBio.01667-14 10.1042/bj2720359 10.1371/journal.ppat.1004265 10.1016/j.ijid.2014.12.031 10.1186/s12934-016-0537-0 10.1016/j.ijantimicag.2017.03.020 10.1007/s10863-012-9425-4 10.1158/1940-6207.CAPR-11-0338 10.1038/ncomms5730 10.1002/0471142735.im1401s83 10.1093/jac/dkg301 10.1021/bi2007299 |
ContentType | Journal Article |
Copyright | The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. |
Copyright_xml | – notice: The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2019 – notice: The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. |
DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION 7X8 5PM |
DOI | 10.1093/jac/dky555 |
DatabaseName | 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 - Academic MEDLINE |
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 |
EISSN | 1460-2091 |
EndPage | 920 |
ExternalDocumentID | 10_1093_jac_dky555 30689890 10.1093/jac/dky555 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GrantInformation_xml | – fundername: Council of Scientific and Industrial Research funderid: 10.13039/501100001412 – fundername: NIAID funderid: 10.13039/100000060 – fundername: Department of Biotechnology funderid: 10.13039/501100010803 – fundername: Department of Biotechnology grantid: BT/PR13469/BRB/10/1396/2015; BT/HRD/NBA/37/01/2014 funderid: 10.13039/501100010803 – fundername: NIH grantid: NR 119 funderid: 10.13039/100000002 – fundername: NINR NIH HHS grantid: R03 NR010193 – fundername: NINR NIH HHS grantid: R43 NR010191 – fundername: ; ; ; – fundername: ; ; ; grantid: NR 119 – fundername: ; ; ; grantid: BT/PR13469/BRB/10/1396/2015; BT/HRD/NBA/37/01/2014 |
GroupedDBID | --- -E4 .2P .I3 .XZ .ZR 0R~ 18M 1TH 29J 2WC 4.4 482 48X 53G 5GY 5RE 5VS 5WA 5WD 70D AABZA AACZT AAJKP AAMVS AAOGV AAPNW AAPQZ AAPXW AARHZ AASNB AAUAY AAUQX AAVAP AAWTL ABEUO ABIXL ABJNI ABKDP ABLJU ABNHQ ABNKS ABPTD ABQLI ABQNK ABWST ABXVV ABZBJ ACCCW ACGFO ACGFS ACIWK ACPRK ACUFI ACUTJ ACUTO ACYHN ADBBV ADEYI ADEZT ADGZP ADHKW ADHZD ADIPN ADJQC ADOCK ADQBN ADRIX ADRTK ADVEK ADYVW ADZXQ AEGPL AEJOX AEKSI AEMDU AENEX AENZO AEPUE AETBJ AEWNT AFFZL AFIYH AFOFC AFRAH AFXAL AFXEN AGINJ AGKEF AGQXC AGSYK AGUTN AHMBA AHXPO AIAGR AIJHB AJEEA ALMA_UNASSIGNED_HOLDINGS ALUQC APIBT APWMN ATGXG AXUDD BAWUL BAYMD BCRHZ BEYMZ BHONS BTRTY BVRKM C45 CDBKE CS3 CZ4 DAKXR DIK DILTD DU5 D~K E3Z EBS ECGQY EE~ EJD EMOBN ENERS F5P F9B FECEO FLUFQ FOEOM FOTVD FQBLK GAUVT GJXCC GX1 H13 H5~ HAR HH5 HW0 HZ~ IOX J21 JXSIZ KAQDR KBUDW KOP KQ8 KSI KSN L7B M-Z M49 MHKGH ML0 N9A NGC NOMLY NOYVH NU- O9- OAUYM OAWHX OBS OCZFY ODMLO OJQWA OJZSN OK1 OPAEJ OVD OWPYF P2P PAFKI PEELM PQQKQ Q1. Q5Y R44 RD5 RHF ROL ROX ROZ RUSNO RW1 RXO TCURE TEORI TJX TMA TR2 UCJ W8F WOQ X7H YAYTL YKOAZ YXANX ZKX ~91 CGR CUY CVF ECM EIF NPM AAYXX CITATION 7X8 ABSAR 5PM |
ID | FETCH-LOGICAL-c408t-a7b6f00dd80d6b9840dfcf622dd880f4487fdfaae3a6feaa3a3e565c57130d653 |
ISSN | 0305-7453 1460-2091 |
IngestDate | Tue Sep 17 21:16:48 EDT 2024 Sat Aug 17 04:32:36 EDT 2024 Thu Sep 12 16:30:57 EDT 2024 Sun Oct 13 09:27:45 EDT 2024 Wed Sep 11 04:48:51 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 4 |
Language | English |
License | This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c408t-a7b6f00dd80d6b9840dfcf622dd880f4487fdfaae3a6feaa3a3e565c57130d653 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Ajay Kumar, Vishant Mahendra Boradia and Ritesh Thakare authors made an equal contribution. Sidharth Chopra and Chaaya Iyengar Raje authors made an equal contribution. |
OpenAccessLink | https://europepmc.org/articles/pmc6419618?pdf=render |
PMID | 30689890 |
PQID | 2179413361 |
PQPubID | 23479 |
PageCount | 9 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_6419618 proquest_miscellaneous_2179413361 crossref_primary_10_1093_jac_dky555 pubmed_primary_30689890 oup_primary_10_1093_jac_dky555 |
PublicationCentury | 2000 |
PublicationDate | 2019-04-01 |
PublicationDateYYYYMMDD | 2019-04-01 |
PublicationDate_xml | – month: 04 year: 2019 text: 2019-04-01 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | England |
PublicationPlace_xml | – name: England |
PublicationTitle | Journal of antimicrobial chemotherapy |
PublicationTitleAlternate | J Antimicrob Chemother |
PublicationYear | 2019 |
Publisher | Oxford University Press |
Publisher_xml | – name: Oxford University Press |
References | ( key 2019031509373476200_dky555-B4) 2012 Rúa ( key 2019031509373476200_dky555-B14) 1990; 272 Mehrotra ( key 2019031509373476200_dky555-B21) 2014; 10 Martin ( key 2019031509373476200_dky555-B3) 2009 Shi ( key 2019031509373476200_dky555-B22) 2015; 5 Maitra ( key 2019031509373476200_dky555-B1) 2015; 32 Quartararo ( key 2019031509373476200_dky555-B13) 2011; 50 Sharma ( key 2019031509373476200_dky555-B17) 2000; 7 Kwasny ( key 2019031509373476200_dky555-B15) 2010; 50 Pedersen ( key 2019031509373476200_dky555-B19) 2012; 44 Boradia ( key 2019031509373476200_dky555-B23) 2014; 5 Rangel-Vega ( key 2019031509373476200_dky555-B2) 2015; 6 Zhang ( key 2019031509373476200_dky555-B5) 2008; 81 Trouplin ( key 2019031509373476200_dky555-B6) 2013; 81 Odds ( key 2019031509373476200_dky555-B8) 2003; 52 Smith ( key 2019031509373476200_dky555-B11) 2003; 278 Ji ( key 2019031509373476200_dky555-B12) 2011; 7 Shoshan ( key 2019031509373476200_dky555-B18) 2012; 44 Thakare ( key 2019031509373476200_dky555-B7) 2017; 50 Ganapathy-Kanniappan ( key 2019031509373476200_dky555-B16) 2009; 29 Foulston ( key 2019031509373476200_dky555-B24) 2014; 5 Modun ( key 2019031509373476200_dky555-B25) 1999; 67 Kitz ( key 2019031509373476200_dky555-B10) 1962; 237 Boradia ( key 2019031509373476200_dky555-B9) 2016; 15 Zhang ( key 2019031509373476200_dky555-B20) 2012; 5 |
References_xml | – volume: 7 start-page: 663. year: 2000 ident: key 2019031509373476200_dky555-B17 article-title: Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis publication-title: Nat Struct Biol doi: 10.1038/77964 contributor: fullname: Sharma – volume: 278 start-page: 1735 year: 2003 ident: key 2019031509373476200_dky555-B11 article-title: Biochemical and structural studies of malate synthase from Mycobacterium tuberculosis publication-title: J Biol Chem doi: 10.1074/jbc.M209248200 contributor: fullname: Smith – volume: 44 start-page: 7 year: 2012 ident: key 2019031509373476200_dky555-B18 article-title: 3-Bromopyruvate: targets and outcomes publication-title: J Bioenerg Biomembr doi: 10.1007/s10863-012-9419-2 contributor: fullname: Shoshan – volume: 237 start-page: 3245 year: 1962 ident: key 2019031509373476200_dky555-B10 article-title: Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase publication-title: J Biol Chem doi: 10.1016/S0021-9258(18)50153-8 contributor: fullname: Kitz – volume: 7 start-page: 376. year: 2011 ident: key 2019031509373476200_dky555-B12 article-title: Identification of mannich base as a novel inhibitor of Mycobacterium tuberculosis isocitrate by high-throughput screening publication-title: Int J Biol Sci doi: 10.7150/ijbs.7.376 contributor: fullname: Ji – volume: 5 start-page: 18176 year: 2015 ident: key 2019031509373476200_dky555-B22 article-title: Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs publication-title: Sci Rep doi: 10.1038/srep18176 contributor: fullname: Shi – volume: 29 start-page: 4909 year: 2009 ident: key 2019031509373476200_dky555-B16 article-title: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pyruvylated during 3-bromopyruvate mediated cancer cell death publication-title: Anticancer Res contributor: fullname: Ganapathy-Kanniappan – volume: 67 start-page: 1086 year: 1999 ident: key 2019031509373476200_dky555-B25 article-title: The staphylococcal transferrin-binding protein is a cell wall glyceraldehyde-3-phosphate dehydrogenase publication-title: Infect Immun doi: 10.1128/IAI.67.3.1086-1092.1999 contributor: fullname: Modun – volume: 6 start-page: 282 year: 2015 ident: key 2019031509373476200_dky555-B2 article-title: Drug repurposing as an alternative for the treatment of recalcitrant bacterial infections publication-title: Front Microbiol doi: 10.3389/fmicb.2015.00282 contributor: fullname: Rangel-Vega – volume-title: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically—Ninth Edition: Approved Standard M07-A9 year: 2012 ident: key 2019031509373476200_dky555-B4 – volume: 50 start-page: 13A.8.1 year: 2010 ident: key 2019031509373476200_dky555-B15 article-title: Static biofilm cultures of Gram-positive pathogens grown in a microtiter format used for anti-biofilm drug discovery publication-title: Curr Protoc Pharmacol doi: 10.1002/0471141755.ph13a08s50 contributor: fullname: Kwasny – volume: 5 start-page: e01667 year: 2014 ident: key 2019031509373476200_dky555-B24 article-title: The extracellular matrix of Staphylococcus aureus biofilms comprises cytoplasmic proteins that associate with the cell surface in response to decreasing pH publication-title: mBio doi: 10.1128/mBio.01667-14 contributor: fullname: Foulston – volume: 272 start-page: 359 year: 1990 ident: key 2019031509373476200_dky555-B14 article-title: Isocitrate lyase from Phycomyces blakesleeanus. The role of Mg2+ ions, kinetics and evidence for two classes of modifiable thiol groups publication-title: Biochem J doi: 10.1042/bj2720359 contributor: fullname: Rúa – volume: 10 start-page: e1004265. year: 2014 ident: key 2019031509373476200_dky555-B21 article-title: Pathogenicity of Mycobacterium tuberculosis is expressed by regulating metabolic thresholds of the host macrophage publication-title: PLoS Pathog doi: 10.1371/journal.ppat.1004265 contributor: fullname: Mehrotra – volume: 32 start-page: 50 year: 2015 ident: key 2019031509373476200_dky555-B1 article-title: Repurposing—a ray of hope in tackling extensive drug resistance in tuberculosis publication-title: Int J Infect Dis doi: 10.1016/j.ijid.2014.12.031 contributor: fullname: Maitra – volume: 15 start-page: 140 year: 2016 ident: key 2019031509373476200_dky555-B9 article-title: Mycobacterium tuberculosis H37Ra: a surrogate for the expression of conserved, multimeric proteins of M.tb H37Rv publication-title: Microb Cell Fact doi: 10.1186/s12934-016-0537-0 contributor: fullname: Boradia – volume: 50 start-page: 389 year: 2017 ident: key 2019031509373476200_dky555-B7 article-title: Repurposing ivacaftor for treatment of Staphylococcus aureus infections publication-title: Int J Antimicrob Agents doi: 10.1016/j.ijantimicag.2017.03.020 contributor: fullname: Thakare – volume: 44 start-page: 1 year: 2012 ident: key 2019031509373476200_dky555-B19 article-title: Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective ‘small molecule’ anti-cancer agent taken from labside to bedside: introduction to a special issue publication-title: J Bioenerg Biomembr doi: 10.1007/s10863-012-9425-4 contributor: fullname: Pedersen – volume: 5 start-page: 717 year: 2012 ident: key 2019031509373476200_dky555-B20 article-title: Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver toxicity publication-title: Cancer Prev Res doi: 10.1158/1940-6207.CAPR-11-0338 contributor: fullname: Zhang – volume: 5 start-page: 4730 year: 2014 ident: key 2019031509373476200_dky555-B23 article-title: Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin publication-title: Nat Commun doi: 10.1038/ncomms5730 contributor: fullname: Boradia – volume: 81 start-page: e50966 year: 2013 ident: key 2019031509373476200_dky555-B6 article-title: Bone marrow-derived macrophage production publication-title: J Vis Exp contributor: fullname: Trouplin – volume: 81 year: 2008 ident: key 2019031509373476200_dky555-B5 article-title: The isolation and characterization of murine macrophages publication-title: Curr Protoc Immunol doi: 10.1002/0471142735.im1401s83 contributor: fullname: Zhang – volume: 52 start-page: 1. year: 2003 ident: key 2019031509373476200_dky555-B8 article-title: Synergy, antagonism, and what the chequerboard puts between them publication-title: J Antimicrob Chemother doi: 10.1093/jac/dkg301 contributor: fullname: Odds – volume: 50 start-page: 6879 year: 2011 ident: key 2019031509373476200_dky555-B13 article-title: Kinetic and chemical mechanism of malate synthase from Mycobacterium tuberculosis publication-title: Biochemistry doi: 10.1021/bi2007299 contributor: fullname: Quartararo – volume-title: USA: Sloan-Kettering Institute for Cancer Research year: 2009 ident: key 2019031509373476200_dky555-B3 contributor: fullname: Martin |
SSID | ssj0006568 |
Score | 2.3951485 |
Snippet | Abstract
Background
The emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and... The emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and ESKAPE pathogens. In... |
SourceID | pubmedcentral proquest crossref pubmed oup |
SourceType | Open Access Repository Aggregation Database Index Database Publisher |
StartPage | 912 |
SubjectTerms | Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacology Disease Models, Animal Drug Repositioning Enzyme Inhibitors - administration & dosage Enzyme Inhibitors - pharmacology Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - antagonists & inhibitors Mice, Inbred BALB C Microbial Viability - drug effects Mycobacterium tuberculosis - drug effects Original Research Pyruvates - administration & dosage Pyruvates - pharmacology Staphylococcal Infections - drug therapy Staphylococcus aureus - drug effects Transferrin - antagonists & inhibitors Treatment Outcome |
Title | Repurposing ethyl bromopyruvate as a broad-spectrum antibacterial |
URI | https://www.ncbi.nlm.nih.gov/pubmed/30689890 https://www.proquest.com/docview/2179413361/abstract/ https://pubmed.ncbi.nlm.nih.gov/PMC6419618 |
Volume | 74 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwELfKkBAvCMbHysdkBNpLl82JE6d5LAhUIRVN0KG9RZfYVrqydGpTpPJH8DdzjtN8bNP4eLFa17Ga-10vd-7d7wh5i1GPq-UQHM5d7vhSpU6icQgiSMFXAl0kc94x-SzGp_6ns-Cs1_vVylpaF8lR-vPGupL_QRXnEFdTJfsPyNab4gS-RnxxRIRx_CuM0XtGOS3KcF-hxL8PEpNdd7lZrn-gD2l6yICZAumUFZVLk4mcF7PEUjRX2193Tc2ai1lJ0WToQzJ1UdVp1efvdWb26LzJwnmH6iRt8u0309Q5LwYTyFQul7Xtn2YwB3vs_QWd3VV9GP0V7yGzFTeL-aDcvn0g4UatPJZbCh1bdg1NjBP6liP4SFm76wuG0NrGXVvDbNv3VArot6xsVGVe2wd2VFbTXX8WWJ6sc0hxlPNNYOmAr7Br37zwDrnrhVFQsgaPm3BK2NLK-ga2dLcRP8arj-21HQenUzTZil2upuC2fJrpQ_KgQpyOrGY9Ij2V75J7kyrdYpccnFhi880hnTZ1eqtDekBPGsrzzWMyamkiLTWRdjSRwooC7Woi7WjiE3L68cP0_dipmnM4qc-GhQNhIjRjUg6ZFEk09JnUqRaehzNDpjHqD7XUAIqD0AqAA1cYPKRBiF6TFAF_SnbyRa72CGUCDYnkCTetFFgC-M5Dtz11hZaR50OfvNlKNL60HCyxzZ3gMco9tnLvk30U9q0LXm9xiNGGmj_GIFeL9Sr2zFPJ5Vy4ffLM4lLvgyG16bDK-iTsIFYvMPzs3U_yWVbytAvfNf2Unv_pi70g95vf0UuygxioV-jqFsl-qX-_AbRVsyg |
link.rule.ids | 230,315,786,790,891,27955,27956 |
linkProvider | ABC ChemistRy |
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=Repurposing+ethyl+bromopyruvate+as+a+broad-spectrum+antibacterial&rft.jtitle=Journal+of+antimicrobial+chemotherapy&rft.au=Kumar%2C+Ajay&rft.au=Boradia%2C+Vishant+Mahendra&rft.au=Thakare%2C+Ritesh&rft.au=Singh%2C+Alok+Kumar&rft.date=2019-04-01&rft.pub=Oxford+University+Press&rft.issn=0305-7453&rft.eissn=1460-2091&rft.volume=74&rft.issue=4&rft.spage=912&rft.epage=920&rft_id=info:doi/10.1093%2Fjac%2Fdky555&rft.externalDocID=10.1093%2Fjac%2Fdky555 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0305-7453&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0305-7453&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0305-7453&client=summon |