Journal article
The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms
Biofilms are reported to be inherently refractory toward antimicrobial attack and, therefore, cause problems in industrial and medical settings. Pseudomonas aeruginosa biofilms contain subpopulations that exhibit high metabolic activity and subpopulations that exhibit low metabolic activity. We have found that membrane-targeting antimicrobials such as colistin, EDTA, SDS, and chlorhexidine specifically kill the inactive subpopulation in P. aeruginosa biofilms, whereas the active subpopulation survives exposure to these compounds.
Because treatment of P. aeruginosa biofilms with the membrane-targeting compounds colistin, EDTA, SDS, and chlorhexidine resulted in the same spatial distribution of live and dead bacteria, we investigated whether tolerance to these compounds originated from the same molecular mechanisms. Development of colistin-tolerant subpopulations was found to depend on the pmr genes encoding lipopolysaccharide modification enzymes, as well as on the mexAB-oprM, mexCD-oprJ, and muxABC-opmB genes encoding antimicrobial efflux pumps, but does not depend on the mexPQ-opmE efflux pump genes.
Development of chlorhexidine-tolerant subpopulations was found to depend on the mexCD-oprJ genes, but does not depend on the pmr, mexAB-oprM, mexPQ-opmE, or muxABC-opmB genes. Tolerance to SDS and EDTA in P. aeruginosa biofilms is linked to metabolically active cells, but does not depend on the pmr, mexAB, mexCD, mexPQ, or muxABC genes.
Our data suggest that the active subpopulation in P. aeruginosa biofilms is able to adapt to exposure to membrane-targeting agents through the use of different genetic determinants, dependent on the specific membrane-targeting compound.
Language: | English |
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Year: | 2012 |
Pages: | 245-256 |
ISSN: | 1574695x and 09288244 |
Types: | Journal article |
DOI: | 10.1111/j.1574-695X.2012.00929.x |
ORCIDs: | Pamp, Sünje Johanna , 0000-0001-6251-9842 , 0000-0001-5004-8609 and 0000-0002-9751-474X |
03502, Genetics - General 10060, Biochemistry studies - General 10064, Biochemistry studies - Proteins, peptides and amino acids 12512, Pathology - Therapy 22002, Pharmacology - General 31000, Physiology and biochemistry of bacteria 31500, Genetics of bacteria and viruses 38502, Chemotherapy - General, methods and metabolism 38504, Chemotherapy - Antibacterial agents Biochemistry and Molecular Biophysics EDTA 60-00-4 antibacterial-drug, antiinfective-drug Gram-Negative Aerobic Rods and Cocci Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Pseudomonadaceae [06508] Pseudomonas aeruginosa species Infection Molecular Genetics Pharmacology Pseudomonas aeruginosa biofilm infection bacterial disease drug therapy, etiology Pseudomonas aeruginosa mexAB gene [Pseudomonadaceae] expression Pseudomonas aeruginosa mexAB-oprM gene [Pseudomonadaceae] expression Pseudomonas aeruginosa mexCD gene [Pseudomonadaceae] expression Pseudomonas aeruginosa mexCD-oprJ gene [Pseudomonadaceae] expression Pseudomonas aeruginosa mexPQ gene [Pseudomonadaceae] expression Pseudomonas aeruginosa mexPQ-opmE gene [Pseudomonadaceae] expression Pseudomonas aeruginosa muxABC gene [Pseudomonadaceae] expression Pseudomonas aeruginosa muxABC-opmB gene [Pseudomonadaceae] expression Pseudomonas aeruginosa pmr gene [Pseudomonadaceae] expression SDS antibacterial-drug, antiinfective-drug antimicrobial tolerance chlorhexidine 55-56-1 antibacterial-drug, antiinfective-drug colistin 1066-17-7 antibacterial-drug, antiinfective-drug combination therapy therapeutic and prophylactic techniques, clinical techniques lipopolysaccharide modification enzyme molecular mechanism