SPECIAL TOPIC: BIODIVERSITY Simon Silver Æ Le T. Phung A bacterial view of the periodic table: genes and proteins for toxic inorganic ions Received: 11 April 2005 / Accepted: 11 July 2005 Ó Society for Industrial Microbiology 2005 Abstract Essentially all bacteria have genes for toxic metal ion resistances and these include those for Ag + , AsO 2  , AsO 4 3 , Cd 2+ , Co 2+ , CrO 4 2 , Cu 2+ , Hg 2+ , Ni 2+ , Pb 2+ , TeO 3 2 , Tl + and Zn 2+ . The largest group of resistance systems functions by energy-dependent efflux of toxic ions. Fewer involve enzymatic transformations (oxidation, reduction, methylation, and demethylation) or metal-binding proteins (for example, metallothionein SmtA, chaperone CopZ and periplasmic silver binding protein SilE). Some of the efflux resistance systems are ATPases and others are chemiosmotic ion/proton exchangers. For example, Cd 2+ -efflux pumps of bacteria are either inner membrane P-type ATPases or three polypeptide RND chemiosmotic complexes consisting of an inner membrane pump, a periplasmic-bridging pro- tein and an outer membrane channel. In addition to the best studied three-polypeptide chemiosmotic system, Czc (Cd 2+ , Zn 2+ , and Co 2 ), others are known that ef- flux Ag + , Cu + , Ni 2+ , and Zn 2+ . Resistance to inor- ganic mercury, Hg 2+ (and to organomercurials, such as CH 3 Hg + and phenylmercury) involve a series of metal- binding and membrane transport proteins as well as the enzymes mercuric reductase and organomercurial lyase, which overall convert more toxic to less toxic forms. Arsenic resistance and metabolizing systems occur in three patterns, the widely-found ars operon that is present in most bacterial genomes and many plasmids, the more recently recognized arr genes for the periplas- mic arsenate reductase that functions in anaerobic res- piration as a terminal electron acceptor, and the aso genes for the periplasmic arsenite oxidase that functions as an initial electron donor in aerobic resistance to arsenite. Keywords Toxic metal resistances Æ Arsenic Æ Mercury Æ Cadmium Æ Bacterial plasmids Introduction Toxic heavy metals have been abundant on the planet Earth and microbes have been exposed to them (for example the cations of Hg and the oxyanions of As) since basically the beginning of life, nearly 4 billion years ago. Thus the question of whether toxic metal (and oxyanions of some soft metals) resistance systems evolved in microbes in response to human pollution in the last few hundreds or thousands of years is easily answered in the negative. These resistance determinants have been here for billions of years; and the arguments supporting such a broad and untestable assertion needs to be addressed element by element. The primary basis for this conclusion is the abundance and wide spread occurrence of such resistance systems, from bacterial type to type and with frequencies ranging from a few percent in ‘‘pristine’’ environments to nearly all isolates from heavily polluted environments. The DNA and amino acid sequences and structures of the genes and proteins concerned with arsenic resistance indicate an ancient origin [56], although it is premature to conclude whether early ‘‘bio-available’’ As occurred as As(III) or as As(V). Genetic and mechanistic studies of toxic metal ion resistance systems have been reviewed frequently over the last 30 years. We will not cite earlier reviews and reports of all toxic metal resistances (before [96, 98, 101]), but rather cite newer metal-by-metal reviews, best found now in a focused issue of FEMS Microbiol. Rev. [17] plus newer major findings that expand or complete our picture of how bacteria cope with toxic metal stress. However, some elements have been chosen for deeper consideration within space limits, as they provide mod- els for study of resistance to other elements, while others are only considered in passing, usually because we lack the needed understanding or because little progress has S. Silver (&) Æ L. T. Phung (&) Department of Microbiology and Immunology, University of Illinois, Chicago, IL, 60612 USA E-mail: Simon@uic.edu; LePhung@uic.edu Tel.: +1-312-9969608 Fax: +1-312-9966415 J Ind Microbiol Biotechnol (2005) DOI 10.1007/s10295-005-0019-6