Bacteria Under Metal Stress-Molecular Mechanisms of Metal Tolerance

Abstract

Metals are natural components of the lithosphere, whose amounts and bioavailability are increasing in many areas due to their continuous release from both natural sources and intensive human activities. Some metals are essential or beneficial for living organisms, while others are non-essential and potentially toxic. When present at higher concentrations, even essential and beneficial metal ions can become harmful to all forms of life. Bacteria, unicellular organisms that have been exposed to metals since the earliest stages of life on Earth, have evolved metabolic pathways involving essential metals as well as diverse strategies to cope with metal toxicity. In the domain Bacteria, two main strategies have been identified: (i) metal exclusion, which includes cell wall sequestration and immobilization of metals in extracellular exopolysaccharides, siderophores, and other soluble microbial products, as well as (ii) metal tolerance, involving intracellular sequestration of metals (e.g., by metallothioneins, or low molecular weight thiols) as well as enzymatic conversion of metals to less toxic forms and/or its active efflux. Microorganisms possessing such adaptive traits are considered valuable agents for potential application in medicine, environmental sciences, and bioengineering (e.g., bioremediation and/or biomining).

Keywords: enzymatic detoxification; exopolysaccharides; metal efflux; metallothionein; siderophores.

Figure 1

Bacterial mechanisms of metal exclusion (A), including cell wall sequestration (1), extracellular sequestration by exopolysaccharides (2), siderophores (3), and soluble microbial products (SMP) (4) as well as metal tolerance (B), including intracellular sequestration by metallothioneins (MT) (5) or other ligands (e.g., free amino acids, glutathione, or chaperones) (6), enzymatic conversion (7), and efflux of metals (8). Abbreviations: Cd—cadmium, Cu—copper, Hg—mercury, -SH—thiol group of cysteine, MerA—mercury reductase, CopA-D—proteins involved in copper transport.

Figure 2

Bacterial siderophores classified by chemical structure: carboxylate type (e.g., achromobactin), catechol type (e.g., bacillibactin and enterobactin), and hydroxamate type (e.g., aerobactin and putrebactin).

Figure 3

Bacterial operons involved in metal efflux. P/O—promoter/operator site. The mer operon: merR encodes the MerR regulatory protein, which activates the promoter in the presence of Hg²⁺ and represses it in its absence; merD encodes MerD, another regulator protein; merA encodes MerA, a mercuric reductase enzyme; merB encodes MerB, an organomercury lyase; merC, mer E-G, and merT encode membrane-associated proteins (MerC, MerE-G, and MerT) involved in Hg²⁺ transport from the membrane into the cytoplasm; ORF (open reading frames). The ars operon: arsR and arsD encode regulatory proteins ArsR and ArsD; arsA encodes ArsA, an intramembrane ATPase that provides energy for As³⁺ efflux; arsB encodes ArsB, a membrane-associated oxyanion-stimulated ATPase protein; arsC encodes ArsC, an arsenate reductase. The cop operon: copR and copS encode regulatory proteins CopR and CopS; copA-D encode membrane and periplasmic proteins CopA-D involved in Cu²⁺ transport. The czc operon: czcD and czcR encode regulatory proteins CzcD and CzcR; czcA encodes CzcA, an inner membrane protein; czcC encodes CzcC, an outer membrane protein; czcB encodes CzcB, a periplasmic protein that connects CzcA and CzcC. The cad operon: cadA encodes CadA, a membrane pump responsible for active Cd²⁺ efflux; cadB encodes CadB, which is involved in Cd²⁺ accumulation in the membrane; cadC encodes CadC, involved in Cd²⁺ transport into CadA; cadD encodes CadD, which regulates cadA expression. Based on [156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200].