The Diversity of Microbial Responses to Nitric Oxide and Agents of Nitrosative Stress: Close Cousins but Not Identical Twins
Section snippets
Overview
Nitric oxide (NO) is a small and freely diffusible species once known primarily as a toxic component of air pollution. In physiology and biochemistry, it was well known as a poison and ligand for heme proteins. The discovery of the enzymic generation of NO in mammalian systems and its cell signaling functions represents a watershed moment in the evolution of our understanding of biological signal transduction. The importance of NO as a molecule of real biological significance cannot, however,
Historical Perspective
The modern era of NO research may be considered to begin in the 1980s when NO was identified as the endothelium-derived relaxing factor (EDRF). This remarkable story and its culmination in a Nobel Prize and the designation of NO as “molecule of the year” by Science in 1992 are covered well elsewhere, especially in accounts by the laureates (Furchgott, 1999, Ignarro, 1999, Ignarro, 2005, Murad, 1999). NO was also shown to participate in the regulation of the nervous and immune systems, and it
Nitrite Reduction and Denitrification
The major source of NO in man is via the action of NOS (see Section 3.3), but other sources should be briefly considered. Nitrite is protonated under acidic conditions (as in the stomach) and the resulting nitrous acid will yield NO and other nitrogen oxides; the beneficial effects of acidified nitrite in killing ingested pathogens, gastric mucosal integrity and other effects are discussed elsewhere (Lundberg et al., 2004). Acidified nitrite is sometimes, but perhaps not ideally, used as a
NO, Its Redox Chemistry, and NO2
The biological chemistry of NO and derived/related molecules is potentially complex due to a multitude of species that can be generated from NO in a biological milieu and the multiple possible reaction targets associated with these derived species (for an overview, see Lehnert and Scheidt, 2010). Moreover, the fate and disposition of NO is always a function of its biochemical environment, which can vary significantly even within a single cell. The redox relationship between NO and
Laboratory Methods
Working with many of the nitrogen oxides described above can be accomplished using either authentic compounds, or in many cases, it is more convenient to use donor species. Herein, we discuss briefly aspects of working with the nitrogen oxides that appear to be of the most current interest—NO, NO2, N2O3, NO2−, HNO, and ONOO−. For several nitrogen oxide species discussed below, the use of donor compounds is prevalent and even necessary. There are several important factors that need to be
Targets of RNS in Microorganisms
It is frequently stated that NO is a highly reactive gas and must interact with numerous and diverse biological targets. In fact, as we outline in Section 4.1, NO is not especially reactive but it is true that its targets are not as restricted as those of another “gasotransmitter,” carbon monoxide (CO) (Davidge et al., 2009a). The direct cellular effects of NO are incompletely understood because of the complexity of NO chemistry introduced in Section 4. Nevertheless, various biomolecules are
Global and Systems Approaches to Understanding Responses to NO and RNS
Due to the complex nature of the interactions between microorganisms and various RNS, many studies now utilize a variety of “omic” techniques available to more fully understand the targets of and responses to these stresses. Global/systems approaches have the advantage of being able to highlight predicted as well as unexpected and novel responses of the microbe. These approaches are able to show us the interactions, robustness, and modularity of the complex microbial systems in place for the
Conclusions
The past 15 years have seen a remarkable transformation of our appreciation of the assaults on microbes by NO and RNS and also the elaborate and effective defense measures mounted. Certain recurrent themes are evident. Microbes (in most cases, the information relates to bacteria) are able to resist NO in their environments by a relatively small number of detoxification mechanisms, the best understood being globins that catalyze NO conversion to nitrate and reductases that produce nitroxyl
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