Abstract
Formaldehyde is the simplest of all aldehydes and is highly cytotoxic. Its use and associated dangers from environmental exposure have been well documented. Detoxification systems for formaldehyde are found throughout the biological world and they are especially important in methylotrophic bacteria, which generate this compound as part of their metabolism of methanol. Formaldehyde metabolizing systems can be divided into those dependent upon pterin cofactors, sugar phosphates and those dependent upon glutathione. The more prevalent thiol-dependent formaldehyde detoxification system is found in many bacterial pathogens, almost all of which do not metabolize methane or methanol. This review describes the endogenous and exogenous sources of formaldehyde, its toxic effects and mechanisms of detoxification. The methods of formaldehyde sensing are also described with a focus on the formaldehyde responsive transcription factors HxlR, FrmR, and NmlR. Finally, the physiological relevance of detoxification systems for formaldehyde in bacterial pathogens is discussed.
Highlights
Formaldehyde (H2C = O), structurally the simplest of all aldehydes, is a major byproduct of the manufacturing industry (Heck et al, 1990), a common environmental hazard (Flyvholm and Andersen, 1993; Tang et al, 2009; International Agency for Research on Cancer, 2012), and a product of the cellular metabolism of many methylated compounds
It is clear from this review that the ability to sense and detoxify formaldehyde is not limited to environmental organisms that use methane and methanol as a carbon source
It is likely significant that formaldehyde detoxification pathways are present in host-adapted bacterial pathogens that were not previously expected to encounter formaldehyde during their physiology
Summary
Specialty section: This article was submitted to Microbial Physiology and Metabolism, a section of the journal Frontiers in Microbiology. Formaldehyde is the simplest of all aldehydes and is highly cytotoxic. Detoxification systems for formaldehyde are found throughout the biological world and they are especially important in methylotrophic bacteria, which generate this compound as part of their metabolism of methanol. Formaldehyde metabolizing systems can be divided into those dependent upon pterin cofactors, sugar phosphates and those dependent upon glutathione. The more prevalent thiol-dependent formaldehyde detoxification system is found in many bacterial pathogens, almost all of which do not metabolize methane or methanol. This review describes the endogenous and exogenous sources of formaldehyde, its toxic effects and mechanisms of detoxification. The physiological relevance of detoxification systems for formaldehyde in bacterial pathogens is discussed
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