Assembly and regulation of the chlorhexidine-specific efflux pump AceI
Few antibiotics are effective against Acinetobacter baumannii, one of the most successful pathogens responsible for hospital-acquired infections. Resistance to chlorhexidine, an antiseptic widely used to combat A. baumannii, is effected through the proteobacterial antimicrobial compound efflux (PACE...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2020
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| _version_ | 1826259264559120384 |
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| author | Bolla, JR Howes, AC Fiorentino, F Robinson, CV |
| author_facet | Bolla, JR Howes, AC Fiorentino, F Robinson, CV |
| author_sort | Bolla, JR |
| collection | OXFORD |
| description | Few antibiotics are effective against Acinetobacter baumannii, one of the most successful pathogens responsible for hospital-acquired infections. Resistance to chlorhexidine, an antiseptic widely used to combat A. baumannii, is effected through the proteobacterial antimicrobial compound efflux (PACE) family. The prototype membrane protein of this family, AceI (Acinetobacter chlorhexidine efflux protein I), is encoded for by the aceI gene and is under the transcriptional control of AceR (Acinetobacter chlorhexidine efflux protein regulator), a LysR-type transcriptional regulator (LTTR) protein. Here we use native mass spectrometry to probe the response of AceI and AceR to chlorhexidine assault. Specifically, we show that AceI forms dimers at high pH, and that binding to chlorhexidine facilitates the functional form of the protein. Changes in the oligomerization of AceR to enable interaction between RNA polymerase and promoter DNA were also observed following chlorhexidine assault. Taken together, these results provide insight into the assembly of PACE family transporters and their regulation via LTTR proteins on drug recognition and suggest potential routes for intervention. |
| first_indexed | 2024-03-06T18:47:08Z |
| format | Journal article |
| id | oxford-uuid:0ee5da84-1a49-40f7-ab9d-8947401cf4b1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:47:08Z |
| publishDate | 2020 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:0ee5da84-1a49-40f7-ab9d-8947401cf4b12022-03-26T09:48:24ZAssembly and regulation of the chlorhexidine-specific efflux pump AceIJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0ee5da84-1a49-40f7-ab9d-8947401cf4b1EnglishSymplectic ElementsNational Academy of Sciences2020Bolla, JRHowes, ACFiorentino, FRobinson, CVFew antibiotics are effective against Acinetobacter baumannii, one of the most successful pathogens responsible for hospital-acquired infections. Resistance to chlorhexidine, an antiseptic widely used to combat A. baumannii, is effected through the proteobacterial antimicrobial compound efflux (PACE) family. The prototype membrane protein of this family, AceI (Acinetobacter chlorhexidine efflux protein I), is encoded for by the aceI gene and is under the transcriptional control of AceR (Acinetobacter chlorhexidine efflux protein regulator), a LysR-type transcriptional regulator (LTTR) protein. Here we use native mass spectrometry to probe the response of AceI and AceR to chlorhexidine assault. Specifically, we show that AceI forms dimers at high pH, and that binding to chlorhexidine facilitates the functional form of the protein. Changes in the oligomerization of AceR to enable interaction between RNA polymerase and promoter DNA were also observed following chlorhexidine assault. Taken together, these results provide insight into the assembly of PACE family transporters and their regulation via LTTR proteins on drug recognition and suggest potential routes for intervention. |
| spellingShingle | Bolla, JR Howes, AC Fiorentino, F Robinson, CV Assembly and regulation of the chlorhexidine-specific efflux pump AceI |
| title | Assembly and regulation of the chlorhexidine-specific efflux pump AceI |
| title_full | Assembly and regulation of the chlorhexidine-specific efflux pump AceI |
| title_fullStr | Assembly and regulation of the chlorhexidine-specific efflux pump AceI |
| title_full_unstemmed | Assembly and regulation of the chlorhexidine-specific efflux pump AceI |
| title_short | Assembly and regulation of the chlorhexidine-specific efflux pump AceI |
| title_sort | assembly and regulation of the chlorhexidine specific efflux pump acei |
| work_keys_str_mv | AT bollajr assemblyandregulationofthechlorhexidinespecificeffluxpumpacei AT howesac assemblyandregulationofthechlorhexidinespecificeffluxpumpacei AT fiorentinof assemblyandregulationofthechlorhexidinespecificeffluxpumpacei AT robinsoncv assemblyandregulationofthechlorhexidinespecificeffluxpumpacei |