Toward a molecular understanding of fluoride stress in a model Pseudomonas strain

Chemical and biological understanding of fluorine in its many forms has lagged behind that of the other halogens, but studies on fluorine have recently come to the forefront. Thousands of commercial fluorine-containing materials are now found throughout the fabric of society, prompting new concerns regarding their health and environmental impacts. The utility and fate of many fluorine-containing products are inextricably linked to microbial responses to the element in its various forms. In this issue, the paper by Calero et al. (2022) provides new insights into the response of the model soil bacterium Pseudomonas putida KT2440 to fluoride anion. The study takes a broad approach to paint a picture of how fluoride impacts the bacterium and the microorganism’s physiological reaction. Methods employed include fluoride toxicity assays, Tn-Seq, genetic knockouts, fluorescent sensing of fluoride intracellularly and metabolomics. Clearly, microbes like P. putida KT2440 have evolved multiple mechanisms to protect themselves from toxic fluoride anion. Fluorine is the 13th most abundant element in the Earth’s crust but the unavailability of mineral forms and its cellular toxicity has limited the element in bacteria. A review article compiling information on the 33 most abundant elements in prokaryotes did not detect fluorine, showing it to be less prevalent than cadmium, tin and barium in the organisms examined (Novoselov et al., 2013). However, a select few bacteria and plants have learned to sequester fluoride for the purpose of biosynthesizing monofluorinated anti-metabolites as toxins that ward off predators (Chan & O’Hagan, 2012; Walker & Chang, 2014). There is currently interest in producing new fluorinated compounds using the enzyme fluorinase (Calero et al., 2020; O’Hagan & Deng, 2015; Pardo et al., 2022) and this is one of the potential outgrowths of the present work by Calero et al. The scarcity of naturally biosynthesized fluorinated compounds by microbes and plants likely emanates at least partly from cellular toxicity of the mineral acid hydrogen fluoride, HF, and its dissociated anion, fluoride. Humans tragically experienced the toxicity of fluorine gas (F2) and HF in 19th-century laboratories (Weeks, 1932). Henri Moissan was honoured with the Nobel Prize in Chemistry in 1906 for his innovations in safer handling of fluorine but unfortunately died several months after receipt of the award. Subsequent to Moissan, there was a great expansion in industrial uses of fluorine, leading to Freon refrigerants, Teflon-type polymers, specialized surfactants, and most recently, agrichemicals and pharmaceuticals (Dolbier Jr, 2005; Lombardo, 1981). Unlike F2 and HF, many commercial organofluorine compounds are largely unreactive with microbial enzymes, leading to an undesirable environmental persistence (Wackett, 2021). Most industrial fluorine today derives from the mineral fluorite (CaF2). CaF2 is converted to HF and salts of the conjugate base, fluoride anion. Fluoride is used in the types of organofluorine synthesis previously mentioned, as well as aluminium extraction, steel hardening and water fluoridation (Pelham, 1985). Related to the latter, fluoride is added to toothpastes to harden teeth and inhibit caries-causing oral bacteria such as Streptococcus mutans (Marquis, 1995). The application of inhibiting microbes points to the major differences in microbiological response to fluoride compared to chloride anion. Chloride anion is abundant in many bacterial cells at concentrations greater than 50 mM and some halophiles prefer molar levels of the anion Received: 20 June 2022 Accepted: 21 June 2022