Induction of a stress response in Lactococcuslactis is associated with a resistance to ribosomally active antibiotics

The acquisition of multidrug resistance in bacteria underlies the failure of antimicrobial therapy, and the emergence of pathogens that are resistant to almost the entire armoury of antibiotics. Among the proteins that can mediate or contribute to the drug-resistance profile in Gram-positive bacteri...

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Bibliographic Details
Published in:The FEBS journal 2011-11, Vol.278 (21), p.4015
Main Authors: Dorrian, James M, Briggs, Deborah A, Ridley, Michael L, Layfield, Robert, Kerr, Ian D
Format: Article
Language:English
Subjects:
Antibiotics
Bacteria
Drug resistance
Molecular biology
Stress response
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Summary:The acquisition of multidrug resistance in bacteria underlies the failure of antimicrobial therapy, and the emergence of pathogens that are resistant to almost the entire armoury of antibiotics. Among the proteins that can mediate or contribute to the drug-resistance profile in Gram-positive bacteria is a subset of ATP-binding cassette proteins that are comprised of a tandem-repeated nucleotide-binding domain. In this study, we expressed one of these NBD2 proteins, LmrC, in an antibiotic-sensitive Gram-positive host strain (Lactococcuslactis) and demonstrated the acquisition of resistance to ribosomally active antibiotics. Mutation of key catalytic residues suggested that the resistance profile was the result of a cellular response, rather than being a function of the NBD2 protein itself. This observation was confirmed by 2D SDS/PAGE, which demonstrated that the expression of the NBD2 protein induced a stress response in L.lactis. A model combining this stress response induction and the acquisition of antibiotic resistance is proposed. Expression of an ATP binding cassette protein, LmrC, in Lactococcuslactis led to an increase in resistance to ribosomally active antibiotics. However, LmrC function did not cause this resistance. Rather, a cellular stress response induced by the expression of LmrC was responsible. A model in which the induction of cellular stress responses leads to antibiotic resistance is presented. [PUBLICATION ABSTRACT]
ISSN:1742-464X
1742-4658
DOI:10.1111/j.1742-4658.2011.08305.x