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Multimetal resistance and tolerance in microbial biofilms

Key Points

  • This Review focuses on the combined action of chemical, physical and physiological phenomena that protect biofilm microorganisms from toxic metal ions. This includes: metabolic heterogeneity that is introduced by community structure; intercellular signalling events that contribute to the biofilm lifestyle; metal-ion immobilization by biosorption; bioinorganic reactions of metal ions with microbial metabolites; adaptive stress responses; persister cells; and genetic rearrangements or mutations that produce variant phenotypes.

  • Different metal species have distinct chemistries and can poison cells through multiple biochemical pathways. Correlations between susceptibility data and metal-ion physicochemical parameters suggest that chemical mechanisms of toxicity differ between planktonic and biofilm cells.

  • The co-selection of genetic and biochemical pathways might be involved in multimetal and multidrug resistance and/or tolerance.

  • The evidence reviewed here suggests that multimetal resistance (MMR) and tolerance (MMT) may be linked to phenotypic variation among cells in the biofilm population.

  • We propose a multifactorial model of biofilm MMR and MMT in which biofilms can withstand metal toxicity by a process of cellular diversification that is ongoing within the microbial population.

Abstract

Geochemical cycling and industrial pollution have made toxic metal ions a pervasive environmental pressure throughout the world. Biofilm formation is a strategy that microorganisms might use to survive a toxic flux in these inorganic compounds. Evidence in the literature suggests that biofilm populations are protected from toxic metals by the combined action of chemical, physical and physiological phenomena that are, in some instances, linked to phenotypic variation among the constituent biofilm cells. Here, we propose a multifactorial model by which biofilm populations can withstand metal toxicity by a process of cellular diversification.

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Figure 1: Time- and dose-dependent killing of biofilms by metals.
Figure 2: Biochemical mechanisms of microbiological metal toxicity.
Figure 3: Correlation of metal-ion physicochemistry to planktonic-cell and biofilm susceptibility.
Figure 4: Phenotypic variation in Pseudomonas aeruginosa is linked to biofilm multidrug and multimetal resistance.
Figure 5: A multifactorial model of multimetal resistance and tolerance in biofilms.

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Acknowledgements

R.J.T. and H.C. have been supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC). J.J.H. has been supported by the NSERC through a Canada Graduate Scholarship — Doctoral award and by the Alberta Heritage Foundation for Medical Research through a full-time Ph.D. studentship award. The authors would like to thank M. L. Workentine and M. F. Hynes for expert advice and critical reading of this manuscript before submission.

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DATABASES

Entrez Genome Project

Candida albicans

Candida tropicalis

Escherichia coli

Pseudomonas aeruginosa

Pseudomonas fluorescens

Pseudomonas putida

Pseudomonas stutzeri

Staphylococcus aureus

Entrez Protein

P. aeruginosa PA14

FURTHER INFORMATION

Raymond J. Turner's homepage

Howard Ceri's homepage

Comprehensive Environmental Response, Compensation, and Liability Act 2005 Priority List

Glossary

Biofilm

A cell–cell or surface-adherent assemblage of microorganisms that is encased in an extracellular matrix of self-produced polymers.

Differentiation

A developmental process whereby a cell acquires a specialized gene-expression profile that produces a cellular morphology or function that is distinct from the original cell type.

Planktonic cells

A suspension of microorganisms that grow primarily as free-floating, single cells in a liquid medium that is under constant mixing.

Susceptibility

The sensitivity of a microorganism to exposure to a toxic environmental stressor.

Lanthanide

One of the series of 15 f- and d-block elements that have atomic numbers 57–71, from lanthanum to lutetium.

Actinide

One of the series of 15 f- and d-block elements that have atomic numbers 89–103, from actinium to lawrencium, all of which are radioactive.

Multimetal resistance

(MMR). The ability of a microorganism to continue growing in the presence of multiple toxic metal or metalloid cations or oxyanions, either alone or in combination.

Multimetal tolerance

(MMT). The ability of a microorganism to survive, but not grow, in the presence of multiple toxic metal or metalloid cations or oxyanions, either alone or in combination.

Multidrug resistance

(MDR). The ability of a microorganism to continue growing in the presence of multiple, structurally non-related antibiotics, either alone or in combination.

Multidrug tolerance

(MDT). The ability of a microorganism to survive, but not grow, in the presence of multiple, structurally non-related antibiotics, either alone or in combination. This has also been referred to as non-inherited antibiotic resistance.

Minimum bactericidal concentration

(MBC). Conventionally, the concentration of an antimicrobial agent (antibiotic, biocide or metal ion) that kills at least 99.9% of a planktonic (MBCP) or biofilm (MBCB) bacterial population.

Minimum inhibitory concentration

(MIC). The lowest concentration of an antimicrobial agent (antibiotic, biocide or metal ion) that arrests the growth of a planktonic cell population.

Painter-type reaction

A group of thermodynamically favourable reactions between Se and Te oxyanions and the reduced thiol groups of proteins that result in the formation of selenotrisulphides (RS-Se-SR) and tellurotrisulphides (RS-Te-SR), respectively.

Standard reduction potential

(ΔE0). The tendency of a chemical species to acquire electrons from a standard hydrogen electrode at 25°C, 1 atmosphere and at a concentration of 1 M (measured in volts).

Electronegativity

(χ). The ability of an atom, as part of a molecule, to attract electrons towards itself.

Solubility product of the metal–sulphide complex

(pKSP). In a biological context, the measure of a metal ion's affinity for S.

Pearson softness index

A scale that is based on the theory of hard and soft acids and bases. From the viewpoint of biological donor sites, hard ions prefer to bind O or N, soft ions prefer S and borderline ions will bind to O, N or S.

Electron density

The probability that an electron is present at a specific location in an atom or molecule.

Covalent index

The ability of an atom to participate in covalent as opposed to ionic bonds.

Redox poise

The capacity of the biofilm to function in chemical reduction (electron donating or hydrogen accepting) versus oxidation (electron accepting or hydrogen donating) reactions.

Calgary Biofilm Device

(CBD). A batch-culture apparatus for in vitro high-throughput susceptibility testing of microbial biofilms.

Quorum sensing

(QS). A microbial cell–cell communication process that uses small signalling molecules to coordinate population behaviours or regulate genes in response to the concentration of inducers.

Lithification

The process in which sediments are gradually converted under pressure into solid sedimentary rock.

One-dimensional diffusive transport model

A mathematical model that describes the density fluctuations in particles that undergo movements that minimize a concentration gradient.

Siderophore

A Fe-specific chelator that is produced by microorganisms under nutrient-limited conditions as part of a Fe-acquisition system.

Persister cell

A metabolically quiescent cell that neither grows nor dies when exposed to cidal concentrations of antimicrobial compounds.

Toxin–antitoxin module

A chromosomal and plasmid-borne operon that encodes a stable toxic protein or RNA molecule and a labile antitoxin.

Insurance hypothesis

In ecology, the hypothesis that biodiversity insures ecosystems against a decline in their functioning because if many species are present there is a higher chance that some will maintain function even if others fail.

Humic acid

A colloidal mixture of substances that is present in soil and that arises by the microbial degradation of dead biomass. Humic acids are compositionally undefined, but include hydrophobic bioorganics that self-aggregate and chelate multivalent metal ions.

Soluble electron carrier

A water-soluble molecule that shuttles electrons in the microbial respiratory chain by accepting electrons from a donor and transferring them to an acceptor.

Nanowire

An electrically conductive pilus that is composed of bundles of individually conductive filaments that are 10–20 nm in diameter.

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Harrison, J., Ceri, H. & Turner, R. Multimetal resistance and tolerance in microbial biofilms. Nat Rev Microbiol 5, 928–938 (2007). https://doi.org/10.1038/nrmicro1774

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