- Title
- Increasing the PACE of characterising novel transporters by functional genomics
- Creator
- Hassan, Karl A.; Maher, Claire; Elbourne, Liam D. H.; Henderson, Peter J. F.; Paulsen, Ian T.
- Relation
- NHMRC.1060895 http://purl.org/au-research/grants/nhmrc/1060895 & ARC 180100123 http://purl.org/au-research/grants/arc/FT180100123
- Relation
- Current Opinion in Microbiology Vol. 64, p. 1-8
- Publisher Link
- http://dx.doi.org/10.1016/j.mib.2021.08.005
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2021
- Description
- Since the late 1990's the genome sequences for thousands of species of bacteria have been released into public databases. The release of each new genome sequence typically revealed the presence of tens to hundreds of uncharacterised genes encoding putative membrane proteins and more recently, microbial metagenomics has revealed countless more of these uncharacterised genes. Given the importance of small molecule efflux in bacteria, it is likely that a significant proportion of these genes encode for novel efflux proteins, but the elucidation of these functions is challenging. We used transcriptomics to predict that the function of a gene encoding a hypothetical membrane protein is in efflux-mediated antimicrobial resistance. We subsequently confirmed this function and the likely native substrates of the pump by using detailed biochemical and biophysical analyses. Functional studies of homologs of the protein from other bacterial species determined that the protein is a prototype for a family of multidrug efflux pumps - the Proteobacterial Antimicrobial Compound Efflux (PACE) family. The general functional genomics approach used here, and its expansion to functional metagenomics, will very likely reveal the identities of more efflux pumps and other transport proteins of scientific, clinical and commercial interest in the future.
- Subject
- Proteobacterial Antimicrobial Compound Efflux (PACE); genomics; drug resistance; bacterial proteins
- Identifier
- http://hdl.handle.net/1959.13/1446139
- Identifier
- uon:42774
- Identifier
- ISSN:1369-5274
- Language
- eng
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