Functional Linkage between Genes That Regulate Osmotic Stress Responses and Multidrug Resistance Transporters: Challenges and Opportunities for Antibiotic Discovery

被引:26
作者
Cohen, B. Eleazar [1 ]
机构
[1] NIAID, Div Extramural Act, Bethesda, MD 20892 USA
关键词
CATIONIC ANTIMICROBIAL PEPTIDES; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; STAPHYLOCOCCUS-AUREUS; ENVIRONMENTAL-STRESS; MEMBRANE-PROTEINS; ANTIFUNGAL AGENTS; CANDIDA-ALBICANS; DRUG-RESISTANCE; AMPHOTERICIN-B;
D O I
10.1128/AAC.02095-13
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
All cells need to protect themselves against the osmotic challenges of their environment by maintaining low permeability to ions across their cell membranes. This is a basic principle of cellular function, which is reflected in the interactions among ion transport and drug efflux genes that have arisen during cellular evolution. Thus, upon exposure to pore-forming antibiotics such as amphotericin B (AmB) or daptomycin (Dap), sensitive cells overexpress common resistance genes to protect themselves from added osmotic challenges. These genes share pathway interactions with the various types of multidrug resistance (MDR) transporter genes, which both preserve the native lipid membrane composition and at the same time eliminate disruptive hydrophobic molecules that partition excessively within the lipid bilayer. An increased understanding of the relationships between the genes (and their products) that regulate osmotic stress responses and MDR transporters will help to identify novel strategies and targets to overcome the current stalemate in drug discovery.
引用
收藏
页码:640 / 646
页数:7
相关论文
共 64 条
[1]   Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in Saccharomyces cerevisiae [J].
Agarwal, AK ;
Rogers, PD ;
Baerson, SR ;
Jacob, MR ;
Barker, KS ;
Cleary, JD ;
Walker, LA ;
Nagle, DG ;
Clark, AM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (37) :34998-35015
[2]   Large ARF guanine nucleotide exchange factors in membrane trafficking [J].
Anders, N. ;
Juergens, G. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (21) :3433-3445
[3]   Gene Expression and Evolution of Antifungal Drug Resistance [J].
Anderson, James B. ;
Sirjusingh, Caroline ;
Syed, Nazia ;
Lafayette, Shantelle .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2009, 53 (05) :1931-1936
[4]   Lipid rafts function in biosynthetic delivery of proteins to the cell surface in yeast [J].
Bagnat, M ;
Keränen, S ;
Shevchenko, A ;
Shevchenko, A ;
Simons, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3254-3259
[5]   Evolution of antibiotic resistance [J].
Baquero, F ;
Blazquez, J .
TRENDS IN ECOLOGY & EVOLUTION, 1997, 12 (12) :482-487
[6]   Differential expression of over 60 chromosomal genes in Escherichia coli by constitutive expression of MarA [J].
Barbosa, TM ;
Levy, SB .
JOURNAL OF BACTERIOLOGY, 2000, 182 (12) :3467-3474
[7]   Small Multidrug Resistance Protein EmrE Reduces Host pH and Osmotic Tolerance to Metabolic Quaternary Cation Osmoprotectants [J].
Bay, Denice C. ;
Turner, Raymond J. .
JOURNAL OF BACTERIOLOGY, 2012, 194 (21) :5941-5948
[8]   Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway [J].
Belenky, Peter ;
Camacho, Diogo ;
Collins, James J. .
CELL REPORTS, 2013, 3 (02) :350-358
[9]   Intracellular organic osmolytes: Function and regulation [J].
Burg, Maurice B. ;
Ferraris, Joan D. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (12) :7309-7313
[10]   Structure and function of a transcriptional network activated by the MAPK Hog1 [J].
Capaldi, Andrew P. ;
Kaplan, Tommy ;
Liu, Ying ;
Habib, Naomi ;
Regev, Aviv ;
Friedman, Nir ;
O'Shea, Erin K. .
NATURE GENETICS, 2008, 40 (11) :1300-1306