Microbial Drug Efflux Proteins of the Major Facilitator Superfamily

Abstract

Drug efflux proteins are widespread amongst microorganisms, including pathogens. They can contribute to both natural insensitivity to antibiotics and to emerging antibiotic resistance and so are potential targets for the development of new antibacterial drugs. The design of such drugs would be greatly facilitated by knowledge of the structures of these transport proteins, which are poorly understood, because of the difficulties of obtaining crystals of quality. We describe a structural genomics approach for the amplified expression, purification and characterisation of prokaryotic drug efflux proteins of the 'Major Facilitator Superfamily' (MFS) of transport proteins from Helicobacter pylori, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Bacillus subtilis, Brucella melitensis, Campylobacter jejuni, Neisseria meningitides and Streptomyces coelicolor. The H. pylori putative drug resistance protein, HP1092, and the S. aureus QacA proteins are used as detailed examples. This strategy is an important step towards reproducible production of transport proteins for the screening of drug binding and for optimisation of crystallisation conditions to enable subsequent structure determination.

A link between host plant adaptation and pesticide resistance in the polyphagous spider mite Tetranychus urticae

“…Multiple MFS family members were differentially regulated in both Tomato-5G and resistant strains. MFS transporters are single-polypeptide carriers that work in symport/antiport (79,80), and studies in bacteria and fungi have identified roles in the transport of toxic substances (81)(82)(83). For example, overexpression of the mfsM2 gene in a sensitive strain of Botrytis cinerea, a fungal plant pathogen, led to drug-resistance levels similar to those of a fungicide-resistant B. cinerea strain (82).…”

Antibacterial activities of multi drug resistant Myroides odoratimimus bacteria isolated from adult flesh flies (Diptera: Sarcophagidae) are independent of metallo beta-lactamase gene

“…Increased antibiotic resistance in such bacteria where β-lactamase gene subunit is lacking, is mediated by acquiring resistance mechanisms through mutations in bacterial genome or by gaining additional genes through horizontal gene transfer or by physiology dependent resistance. Moreover, bacteria have intrinsic resistance mechanisms that are often not detected in standard antibiotic sensitivity tests performed at laboratory level (26). However, Myroides are linked with low virulence and mortality when it comes to clinical level.…”

Helicobacter pyloriDetection and Antimicrobial Susceptibility Testing

“…In 2006, a putative tetracycline resistance gene, HP1165, which displays identity to the tetracycline efflux gene tetA from Clostridium perfringens was found to be involved in some strains in the inducible tetracycline resistance in H. pylori (309). Several nonspecific multidrug resistance proteins have also been described, but their importance needs to be clarified (279,396,479,541). Apart from resistance to antibiotics, efflux systems in H. pylori play a role in maintaining metal homeostasis, which is crucial for the adaptation of this bacterium to the gastric environment (507).…”