Nutritional Versatility. Versatility as the Ability to Do Many Things

The dogma in microbiology is that microbes are ‘versatile.’ But what does this mean and are they really more versatile than macroorganisms? Certainly bacteria, for instance, can be found almost everywhere—from hot springs, to the ocean floor, to Antarctic ice sheets. Although this has been taken to mean that the Bacteria and Archaea collectively are versatile (in this case with regard to extremes of physical habitat), it says nothing about versatility of the individual species or clone, which is the relevant context here.

From the standpoint of the organism, ‘versatility’ can be adopted in scientific parlance from its common usage in two contexts. First, we say that someone who can do many things—wrestle, play the saxophone, speak several languages, etc.—is versatile. Second, a person who can master different situations or tasks quickly and with apparent ease is said to be versatile. Unlike the first definition, the emphasis in this latter case is on speed of response to new conditions and less on the spectrum of accomplishments. The constraint is time. After all, it can be argued, many things can be accomplished given sufficient time; the truly versatile are those who adjust quickly. Based on these two criteria and the issue of nutritional versatility let us now compare microorganisms with plants and animals. ‘Metabolic’ is used with reference to anabolic and catabolic pathways (in terms of their number and regulation and the metabolites involved) and to the range of substances synthesized or degraded.

Versatility as the Ability to Do Many Things.Evaluated by the first criterion of being able to do many things, both microbes and macroorganisms are highly versatile metabolically with respect to biosyntheses. Despite remarkable advances in genomics and proteomics, all the metabolites, end products, and metabolic pathways for even a single organism are not yet known. The potential metabolic complexity of even a small organism is illustrated by E. coli (about one five-hundredth the size of a plant or animal cell). This is probably the most studied and best understood of all organisms. Its genome has been sequenced, so the number of genes and known or predicted gene functions (4453) are established (Riley et al. 2006; Orth et al. 2011). Approximately 2200 metabolic reactions and more than 1100 unique metabolites have been documented. However, direct evidence exists to date for the function of slightly more than half of the protein-coding gene products, and about one-third of the proteome is functionally not annotated. Metabolic reconstructions for multicellular eukaryotes to date have been relatively few, with a predicted metabolome generally higher than for prokaryotes (de Oliveira Dal’Molin and Nielsen 2013). These data are fluid benchmarks, changing with time as knowledge of the metabolic network becomes increasingly comprehensive. Though small and often misleadingly dismissed as ‘simple’ the bacterial cell is in fact complex in many ways.

Many, perhaps most, bacteria and to a lesser extent fungi can synthesize basically all of the organic compounds they need for cellular macromolecules. In essence they are specialized synthetic chemists, possessing the hundreds of enzymes required to make all their building blocks and polymerizations. As so-called prototrophs they will grow if almost any relatively simple carbon source is available and other conditions are not limiting. E. coli, a facultative inhabitant of the gut, has extraordinary biosynthetic versatility, being able to produce all its cellular components from a simple medium of glucose and mineral salts (including a nitrogen source). This means that a pathway, separate at least in part, exists for each of the 20 amino acids synthesized. In the absence of a sugar, any amino acid can serve as a sole carbon source. The bacterium’s extensive synthetic capability likely reflects characteristics of its habitat—the highly oscillating nutrient realm of the gut, as well as its life elsewhere (see, e.g., Koch 1971; Savageau 1983).

At the other extreme, some bacteria and fungi called auxotrophs lack one or several biosynthetic steps or pathways; as such they are fastidious and require growth factors such as vitamins, amino acids, or purines and pyrimidines in small amounts. Auxotrophs tend to occur in environments of relatively rich media, such as other parts of the human body, where building blocks can consistently be found preformed, obviating the need for synthesis pathways. Such close associates of humans include species of Staphylococcus and Haemophilus. Indeed, they have become auxotrophs because, by living in nutrient-rich environments and under selection pressure, such bacteria have dispensed with redundant biochemical pathways. Instead of a nutritional strategy based on maintaining pathways of biosynthesis for all the building blocks, they have maintained active transport mechanisms capable of efficiently importing end products into their cells (Koch 1995). Another example of a fastidious microbe is the lactic acid bacterium Leuconostoc mesenteroides, which, unlike E. coli, requires a complex culture medium containing yeast extract and peptone as well as glucose. In nature, species of Leuconostoc are found on plant surfaces and in dairy and other food products.

Since degradative pathways are distinct from (not simply the reverse of) biosynthetic pathways, this means that there are also numerous pathways for metabolite degradation. Microbes excel in their degradative capabilities, outstripping those of either plants or animals. Indeed, bacteria collectively can grow in virtually any natural environment and, with few exceptions, can metabolize effectively any organic compound. As such, they have been called ‘metabolically infallible.’ Degradations are frequently accomplished by microbial consortia with intimate and occasionally obligatory interdependencies (such as cross-feeding relationships or syntrophy) among member species (Embree et al. 2015). Degradation pathways, most of which are fairly specific, exist not only for proteins but also for lipids, carbohydrates, and other biopolymers and compounds.

As noted at the outset, these degradative reactions produce key precursor metabolites (plus ATP and reducing power in the form of NADH) through central pathways that are common to all species of bacteria. E. coli and other prokaryotes also have peripheral metabolic pathways, which may be unique to the species or function only where the bacterium grows on compounds that are not part of the central pathway. E. coli has more than 75 such pathways consisting of at least 200-300 different enzymatic reactions (Neidhardt et al. 1990; Lengeler et al. 1999). The number could be expected to exceed this in certain bacteria such as the pseudomonads, which grow on diverse molecules (see Generalists and Specialists, below). Such peripheral pathways illustrate the true nutritional diversity of bacteria.

Plants are even more versatile than heterotrophic bacteria and fungi (note, however, that there are photolithoautotrophic bacteria; recall earlier discussion and Table 3.2). Starting with only CO₂ rather than a sugar as a carbon source, and using water as an electron or hydrogen donor and light instead of chemical energy, plants manufacture an immense array of primary and secondary compounds. Many of these groups, such as the terpenoids, flavo- noids, and alkaloids, are biochemically complex (Chae et al. 2014). Finally, animals, unlike plants or many microorganisms, lack the biochemical machinery to synthesize all their requirements from a few simple molecules such as CO₂ or glucose. Vertebrates, for example, can make only half of the basic 20 amino acids; the others must be supplied in the diet. The complex nutritional requirements of animals are evident in culture, where 13 amino acids, 8 vitamins, and various undefined growth factors supplied by dialyzed serum, in addition to glucose and inorganic salts, are needed in order to grow human (HeLa) cells (Eagle 1955; this basic medium and variations such as that by Dulbecco, persist to this day).

To summarize, by the first definition, nutritional versatility in the case of plants and the bacteria or fungi entails the capacity to synthesize essentially all macromolecules from a few relatively simple, inorganic or organic compounds. In contrast, nutrition for animals generally involves degrading complex food sources, the component units of which are rearranged into new metabolites. While in terms of the ability to do many things this may seem to imply that animals are less versatile than microbes, it does not necessarily: Few microbes synthesize specialized cell types or complex molecules akin to antibodies, eye pigment, neurotransmitters, or any of the vast assortment of other chemicals and structures characteristic of at least the complex metazoans.

These metazoan gene products are often encoded by many spatially separate genes. Such products interact with others in a precisely orchestrated sequence of events to coordinate assembly and function of cells, tissues, organs, and ultimately the entire organism. Microbial biochemical coordination is focused largely at the gene expression and pathway level; for macroorganisms the focus is more at the levels of interaction among gene products and timing of gene activity.