Solvent tolerance in bacteria: role of efflux pumps and cross-resistance with antibiotics
Introduction
Microorganisms are currently exposed to deleterious chemicals naturally occurring in the environment, for example, natural antibiotics, produced by members of microbial communities and detergents such as bile salts, present in the intestinal tract of higher animals. Human activity has further led to the emergence of a plethora of noxious chemicals, either inorganic or organic (xenobiotics) concomitant to industrial activities. Others are chemicals specifically developed to act as antimicrobial agents, such as semisynthetic antibiotics or biocides. The target of the toxic compound may be the cell wall, the cytoplasmic membrane or the biosynthetic pathway of protein and nucleic acid synthesis. The antimicrobial compound may affect the structure of biomembranes or impair biosynthetic pathways essential for microbial growth. Nevertheless, bacteria display outstanding resistance to the action of toxic compounds because of intrinsic long-standing mechanisms that protect cells from continuous exposure to harmful chemicals. In addition to with the metabolism of antimicrobials into non-toxic compounds [1], [2], [3] and the modification of the target site of action [4], the presence of broadly-specific efflux pumps that reduce the concentration of antimicrobials in the cytoplasm to sub-toxic levels has been acknowledged as a major route for microbial resistance to toxic compounds [5], [6], [7]. Although these efflux pumps have been known for some time, its relevance has only recently been acknowledged, particularly since such drug extrusion mechanisms are a major cause of intrinsic bacterial resistance to antibiotics. It is, therefore, logical that most research work in this field has focused on antibiotic efflux pumps [5], [8], [9]. However, it has been clearly shown that some microbial strains, such as Pseudomonas aeruginosa, are tolerant to structurally unrelated antimicrobial agents, such as antibiotics, organic solvents and biocides [9], [10], [11]. The overuse of antibiotics, the escalating use of household products containing biocide agents, and the emission of toxic wastes contribute to the development of drug- and solvent-resistant strains [12], [13], [14], [15], [16], [17], [18], [19], [20]. A deeper insight on the mechanisms of solvent tolerance and its relation to antibiotic tolerance may contribute to broaden the overall knowledge on the inherent properties of bacterial resistance to toxic agents. It may also provide a better approach for the design of new antimicrobial synthetic drugs and biocides, as well as strategies for disinfection procedures, since organic solvents are classical antimicrobial agents [21]. This paper reviews data gathered on microbial tolerance to organic solvents and its relation to antibiotic resistance.
Section snippets
Microbial resistance to organic solvents
The toxicity of an organic solvent is evaluated according to its log Pow (logarithm of the partition coefficient of the solvent in a standard n-octanol/water system). Solvents with log Pow above 5 are biocompatible, whereas solvents with log Pow between 1 and 5 are toxic [22], [23], [24], [25]. Gram-negative bacteria are slightly more tolerant than Gram-positive bacteria. This effect is due to the outer membrane of Gram-negative bacteria which acts as an barrier, particularly to the penetration
Conclusions and perspectives
Efflux pumps play a major role on solvent tolerance in bacteria. Often these protective mechanisms overlap their substrates along a wide range of structurally diverse chemicals. Understanding of the mechanisms of individual and cross resistance may provide effective clues for the design of more effective antimicrobials, combined with a more efficient methodology for the use of known antimicrobials. It may also pave the way for the application of strains tolerant to noxious chemicals in other
Acknowledgements
We thank Professor Leonard Amaral for helpful comments and suggestions. We would also like to thank Dr Miguel Viveiros for helpful discussions.
References (63)
- et al.
Antibiotic efflux pumps
Biochem. Pharmacol.
(2000) Preventing drug access to targets: cell surface permeability barriers and active efflux in bacteria
Semin. Cell Dev. Biol.
(2001)Two-phase partitioning bioreactors: a new technology platform for destroying xenobiotics
Trends Biotechnol.
(2001)- et al.
Estimation of solvent-tolerance of bacteria by the solvent parameter log P
J. Ferment. Bioeng.
(1991) Solvent-tolerant bacteria in biocatalysis
Trends Biotechnol.
(1998)- et al.
Interactions of cyclic hydrocarbons with biological membranes
J. Biol. Chem.
(1994) - et al.
Mechanisms for solvent tolerance in bacteria
J. Biol. Chem.
(1997) Phospholipid modifications in bacteria
Curr. Opin. Microbiol.
(2002)- et al.
Subunit swapping in the Mex-extrusion pumps in Pseudomonas aeruginosa
Biochem. Biophys. Res. Commun.
(1998) - et al.
Identification and molecular characterization of an efflux pump involved in Pseudomonas putida S12 solvent tolerance
J. Biol. Chem.
(1998)