Hassan, KA, Naidu, V, Edgerton, JR et al. (9 more authors) (2019) Short chain diamines are the physiological substrates of PACE family efflux pumps. Proceedings of the National Academy of Sciences of the United States of America, 116 (36). pp. 18015-18020. ISSN 0027-8424
Abstract
Acinetobacter baumannii has rapidly emerged as a major cause of gram-negative hospital infections worldwide. A. baumannii encodes for the transport protein AceI, which confers resistance to chlorhexidine, a widely used antiseptic. AceI is also the prototype for the recently discovered proteobacterial antimicrobial compound efflux (PACE) family of transport proteins that confer resistance to a range of antibiotics and antiseptics in many gram-negative bacteria, including pathogens. The gene encoding AceI is conserved in the core genome of A. baumannii, suggesting that it has an important primordial function. This is incongruous with the sole characterized substrate of AceI, chlorhexidine, an entirely synthetic biocide produced only during the last century. Here we investigated a potential primordial function of AceI and other members of the PACE family in the transport of naturally occurring polyamines. Polyamines are abundant in living cells, where they have physiologically important functions and play multifaceted roles in bacterial infection. Gene expression studies revealed that the aceI gene is induced in A. baumannii by the short-chain diamines cadaverine and putrescine. Membrane transport experiments conducted in whole cells of A. baumannii and Escherichia coli and also in proteoliposomes showed that AceI mediates the efflux of these short-chain diamines when energized by an electrochemical gradient. Assays conducted using 8 additional diverse PACE family proteins identified 3 that also catalyze cadaverine transport. Taken together, these results demonstrate that short-chain diamines are common substrates for the PACE family of transport proteins, adding to their broad significance as a novel family of efflux pumps.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Protected by copyright. This is an author produced version of a paper published in the Proceedings of the National Academy of Sciences of the United States of America. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | drug resistance; polyamines; transport; efflux; PACE family |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number Leverhulme Trust EM-2014-045 EU - European Union PIRSES-GA-2009-247634 EU - European Union Not Known |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Jul 2019 11:26 |
Last Modified: | 30 Jun 2020 15:33 |
Status: | Published |
Publisher: | National Academy of Sciences |
Identification Number: | 10.1073/pnas.1901591116 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:149030 |
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Filename: Figures for text of PNAS paper Hassan et al 2019.pdf
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