Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery
Resistance to β-lactam antibiotics is rapidly growing, substantially due to the spread of serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs), which efficiently catalyse β-lactam hydrolysis. Combinations of a β-lactam antibiotic with an SBL inhibitor have been clinically successful; however,...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2023
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| _version_ | 1797112715527847936 |
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| author | Yang, Y Yan, Y-H Schofield, CJ McNally, A Zong, Z Li, G-B |
| author_facet | Yang, Y Yan, Y-H Schofield, CJ McNally, A Zong, Z Li, G-B |
| author_sort | Yang, Y |
| collection | OXFORD |
| description | Resistance to β-lactam antibiotics is rapidly growing, substantially due to the spread of serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs), which efficiently catalyse β-lactam hydrolysis. Combinations of a β-lactam antibiotic with an SBL inhibitor have been clinically successful; however, no MBL inhibitors have been developed for clinical use. MBLs are a worrying resistance vector because they catalyse hydrolysis of all β-lactam antibiotic classes, except the monobactams, and they are being disseminated across many bacterial species worldwide. Here we review the classification, structures, substrate profiles, and inhibition mechanisms of MBLs, highlighting current clinical problems due to MBL-mediated resistance and progress in understanding and combating MBL-mediated resistance. |
| first_indexed | 2024-03-07T08:27:48Z |
| format | Journal article |
| id | oxford-uuid:8ad2957c-dd13-4e80-9190-cec59655f31b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:27:48Z |
| publishDate | 2023 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:8ad2957c-dd13-4e80-9190-cec59655f31b2024-02-27T08:28:49ZMetallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discoveryJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8ad2957c-dd13-4e80-9190-cec59655f31bEnglishSymplectic ElementsCell Press2023Yang, YYan, Y-HSchofield, CJMcNally, AZong, ZLi, G-BResistance to β-lactam antibiotics is rapidly growing, substantially due to the spread of serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs), which efficiently catalyse β-lactam hydrolysis. Combinations of a β-lactam antibiotic with an SBL inhibitor have been clinically successful; however, no MBL inhibitors have been developed for clinical use. MBLs are a worrying resistance vector because they catalyse hydrolysis of all β-lactam antibiotic classes, except the monobactams, and they are being disseminated across many bacterial species worldwide. Here we review the classification, structures, substrate profiles, and inhibition mechanisms of MBLs, highlighting current clinical problems due to MBL-mediated resistance and progress in understanding and combating MBL-mediated resistance. |
| spellingShingle | Yang, Y Yan, Y-H Schofield, CJ McNally, A Zong, Z Li, G-B Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery |
| title | Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery |
| title_full | Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery |
| title_fullStr | Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery |
| title_full_unstemmed | Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery |
| title_short | Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery |
| title_sort | metallo β lactamase mediated antimicrobial resistance and progress in inhibitor discovery |
| work_keys_str_mv | AT yangy metalloblactamasemediatedantimicrobialresistanceandprogressininhibitordiscovery AT yanyh metalloblactamasemediatedantimicrobialresistanceandprogressininhibitordiscovery AT schofieldcj metalloblactamasemediatedantimicrobialresistanceandprogressininhibitordiscovery AT mcnallya metalloblactamasemediatedantimicrobialresistanceandprogressininhibitordiscovery AT zongz metalloblactamasemediatedantimicrobialresistanceandprogressininhibitordiscovery AT ligb metalloblactamasemediatedantimicrobialresistanceandprogressininhibitordiscovery |