tailieunhanh - Báo cáo khoa hoc : Induction of a stress response in Lactococcus lactis 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. | IFEBS Journal Induction of a stress response in Lactococcus lactis is associated with a resistance to ribosomally active antibiotics James M. Dorrian Deborah A. Briggs Michael L. Ridley Robert Layfield and Ian D. Kerr Schoolof BiomedicalSciences University of Nottingham UK Keywords ABC protein antibiotic resistance heat shock protein proteomics stress Correspondence I. D. Kerr Schoolof BiomedicalSciences University of Nottingham Queen s Medical Centre Nottingham NG7 2UH UK Fax 44 115 8230142 Tel 44 115 8230122 E-mail Received 11 May 2011 revised 24 June 2011 accepted 11 August 2011 doi 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 Lactococcus lactis 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. Introduction The emergence of drug resistance in bacteria and in particular multidrug resistance has become increasingly prominent over the past 30 years and is a growing cause for concern in public health 1 . In Gram-positive bacteria a major class of clinically relevant antibiotics remains the .