Indispensable or toxic? The phosphate versus arsenate debate

Arsenic (As) is toxic, carcinogenic and causes serious health problems. While As occurs naturally due to volcanic activity, the major anthropogenic sources of As are metal processing, burning of coal and arsenic-based pesticides or herbicides. Arsenate (AsO4) and arsenite (AsO3) are the primary chemical forms found in soil. Because of the wide distribution of arsenic compounds, arsenic resistance is widespread among living organisms (Nordstrom, 2002). Most resistance systems reduce arsenate to arsenite and sequester it in a vacuole or expel it from the cell (Stolz et al., 2006). Intensive research has shed light on dissimilatory As (V) reduction and As (III) oxidation pathways. Phosphate is essential to life. Living beings need phosphorus to function, along with other elements such as hydrogen, oxygen, carbon, nitrogen and sulfur. The phosphate ion, PO4, plays several essential cellular roles, such as maintaining the structure of DNA and RNA, combining with lipids to build cell membranes and transporting energy within the cell through the molecule adenosine triphosphate (ATP). During the last two years, the metabolic antagonism that exists between arsenic and phosphorus in microbial metabolism has been the focus of intense study. WolfeSimon and colleagues (2011) revolutionized this area of research by describing the isolation of a bacterial strain, GFAJ-1, capable of thriving in a growth medium containing arsenate and lacking phosphate, hypothesizing that arsenic may substitute phosphorous to allow growth. GFAJ-1 was isolated from highly contaminated sediments and was able to grow in arsenate solution (at 60% the rate of growth in phosphate supplemented medium). Without arsenate or phosphate the strain was unable grow. Thereafter, a number of published works have reported contradictory results to those of Wolfe-Simon et al. Last July, Science published two independent reports on the subject. The work performed by Professor Vorholt’s group (Erb et al., 2012) used highly pure reactives combined elegantly with state-of-the-art chemical tracing techniques to monitor phosphate substitution by arsenate. The findings showed that phosphate is absolutely necessary for the growth of GFAJ-1, suggesting that previous results were misleading due to the presence of impurities in the chemicals used. Although arsenate was found to be combined to biomolecules as sugars or acids in the cultures, they demonstrate that these products are generated abiotically. Furthermore, the authors found no evidence of arsenate incorporation into DNA or other core metabolic molecules. Similar conclusions were drawn by Dr Redfield’s group (Reaves et al., 2012). Their findings showed that the GFAJ-1 strain grows in the complete absence of arsenate and that phosphate is absolutely necessary. Again, chemical impurities are named as the cause of conflicting results of the original GFAJ-1 report (WolfeSimon et al., 2011). Dr Redfield’s group also investigated the putative presence of arsenate in DNA, while doing so using an alternative experimental method. The authors postulated that arsenate incorporation in DNA would result in higher instability. They electrophoretically tested hydrolysis of chromosomal DNA isolated from GFAJ-1 cultures grown under phosphate or arsenate and were unable to detect any significant amount of As in the nucleic acids. Consequently arsenate does not appear to act as a replacement for phosphate in DNA within this strain. Taken together, these results, while not as exceptional as originally thought, still position GFAJ-1 as a strain of great value by virtue of its ability to tolerate arsenate. Thus, the mechanism through which this is achieved represents a highly worthwhile area of study. Of most importance to this topic is the question of how the GFAJ-1 strain is able to glean enough phosphate in *For correspondence. E-mail [email protected]; Tel. (+34) 957 218082; Fax (+34) 957 218688. Microbial Biotechnology (2013) 6(3), 209–211 doi:10.1111/1751-7915.12024 Funding Information No funding information provided. bs_bs_banner