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.

Assembly and regulation of the chlorhexidine-specific efflux pump AceI / Bolla, J. R.; Howes, A. C.; Fiorentino, F.; Robinson, C. V.. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 117:29(2020), pp. 17011-17018. [10.1073/pnas.2003271117]

Assembly and regulation of the chlorhexidine-specific efflux pump AceI

Fiorentino F.;
2020

Abstract

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.
2020
Chlorhexidine; Efflux pumps; Mass spectrometry; Transcriptional regulator; DNA-Directed RNA Polymerases; Drug Resistance, Microbial; Hydrogen-Ion Concentration; Mass Spectrometry; Protein Binding; Protein Multimerization; Protein Subunits; Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Proteins; Chlorhexidine; Membrane Transport Proteins
01 Pubblicazione su rivista::01a Articolo in rivista
Assembly and regulation of the chlorhexidine-specific efflux pump AceI / Bolla, J. R.; Howes, A. C.; Fiorentino, F.; Robinson, C. V.. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 117:29(2020), pp. 17011-17018. [10.1073/pnas.2003271117]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1585449
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