Journal
COMMUNICATIONS BIOLOGY
Volume 2, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-019-0564-6
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Funding
- CREST from the Japan Science and Technology Agency (JST)
- Center of Innovation Program (COI) from the Japan Science and Technology Agency (JST)
- Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation
- Network Joint Research Center for Materials and Devices, Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- MEXT [Kakenhi 18H06103, 19K21223]
- Japan Society for the Promotion of Science (JSPS) [Kakenhi 17H03983, Kakenhi 18K19451]
- Japan Agency for Medical Research and Development (AMED)
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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 beta-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.
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