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Phylogenetic and functional characterisation of the Haemophilus influenzae multidrug efflux pump AcrB.
Commun Biol 2019; 2:340CB

Abstract

Multidrug resistance in Gram-negative bacteria can arise by the over-expression of multidrug efflux pumps, which can extrude a wide range of antibiotics. Here we describe the ancestral Haemophilus influenzae efflux pump AcrB (AcrB-Hi). We performed a phylogenetic analysis of hundreds of RND-type transporters. We found that AcrB-Hi is a relatively ancient efflux pump, which nonetheless can export the same range of antibiotics as its evolved colleague from Escherichia coli. AcrB-Hi was not inhibited by the efflux pump inhibitor ABI-PP, and could export bile salts weakly. This points to an environmental adaptation of RND transporters. We also explain the sensitivity of H. influenzae cells to β-lactams and novobiocin by the outer membrane porin OmpP2. This porin counterbalances the AcrB-Hi efflux by leaking the drugs back into the cells. We hypothesise that multidrug recognition by RND-type pumps is not an evolutionarily acquired ability, and has been present since ancient promiscuous transporters.

Authors+Show Affiliations

1Department of Biomolecular Science and Regulation, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047 Japan.2Laboratory of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047 Japan.1Department of Biomolecular Science and Regulation, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047 Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31531401

Citation

Zwama, Martijn, et al. "Phylogenetic and Functional Characterisation of the Haemophilus Influenzae Multidrug Efflux Pump AcrB." Communications Biology, vol. 2, 2019, p. 340.
Zwama M, Yamaguchi A, Nishino K. Phylogenetic and functional characterisation of the Haemophilus influenzae multidrug efflux pump AcrB. Commun Biol. 2019;2:340.
Zwama, M., Yamaguchi, A., & Nishino, K. (2019). Phylogenetic and functional characterisation of the Haemophilus influenzae multidrug efflux pump AcrB. Communications Biology, 2, p. 340. doi:10.1038/s42003-019-0564-6.
Zwama M, Yamaguchi A, Nishino K. Phylogenetic and Functional Characterisation of the Haemophilus Influenzae Multidrug Efflux Pump AcrB. Commun Biol. 2019;2:340. PubMed PMID: 31531401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phylogenetic and functional characterisation of the Haemophilus influenzae multidrug efflux pump AcrB. AU - Zwama,Martijn, AU - Yamaguchi,Akihito, AU - Nishino,Kunihiko, Y1 - 2019/09/13/ PY - 2019/03/27/received PY - 2019/07/28/accepted PY - 2019/9/19/entrez PY - 2019/9/19/pubmed PY - 2019/9/19/medline KW - Antimicrobial resistance KW - Biochemistry KW - Microbiology SP - 340 EP - 340 JF - Communications biology JO - Commun Biol VL - 2 N2 - Multidrug resistance in Gram-negative bacteria can arise by the over-expression of multidrug efflux pumps, which can extrude a wide range of antibiotics. Here we describe the ancestral Haemophilus influenzae efflux pump AcrB (AcrB-Hi). We performed a phylogenetic analysis of hundreds of RND-type transporters. We found that AcrB-Hi is a relatively ancient efflux pump, which nonetheless can export the same range of antibiotics as its evolved colleague from Escherichia coli. AcrB-Hi was not inhibited by the efflux pump inhibitor ABI-PP, and could export bile salts weakly. This points to an environmental adaptation of RND transporters. We also explain the sensitivity of H. influenzae cells to β-lactams and novobiocin by the outer membrane porin OmpP2. This porin counterbalances the AcrB-Hi efflux by leaking the drugs back into the cells. We hypothesise that multidrug recognition by RND-type pumps is not an evolutionarily acquired ability, and has been present since ancient promiscuous transporters. SN - 2399-3642 UR - https://www.unboundmedicine.com/medline/citation/31531401/Phylogenetic_and_functional_characterisation_of_the_Haemophilus_influenzae_multidrug_efflux_pump_AcrB L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31531401/ DB - PRIME DP - Unbound Medicine ER -