ECOLOGICAL BIOCHEMISTRY - Study Guide - V. M. Isaenko 2005

Chapter 2. ECOLOGICAL AND BIOCHEMICAL INTERACTIONS OF PROKARYOTES, MICROSCOPIC FUNGI, AND ALGAE WITH HIGHER PLANTS AND ANIMALS

2.6. Toxic effects of microorganisms on animals

Bacterial toxins. Among the toxins produced by pathogenic Bacteria, protein exotoxins are the most hazardous, capable of causing severe diseases in mammals, including humans—such as cholera, diphtheria, botulism, and tetanus. They exhibit wide Structural and functional diversity. Most of these toxins are synthesized by bacteria as inactive precursors known as protoxins, which undergo activation to manifest their biological activity. Protein Kinases cleave protoxins to generate fragments that form a bifunctional system. For instance, the molecules of cholera, diphtheria, botulinum, tetanus, and certain other protein toxins consist of linked components: fragment A, which possesses enzymatic activity, and fragment

B, responsible for binding the toxin to Cell-surface receptors and facilitating the translocation of fragment A into the interior of the target cell.

It should be noted that proteolysis of protoxins in pathogenic bacteria is limited. Their activation likely involves a combination of bacterial Proteolytic Enzymes and cellular proteinases.

Unlike simple toxins, which are initially synthesized as a single polypeptide protoxin chain that is subsequently converted into a bifunctional system via proteolysis, complex toxins feature active and receptor domains synthesized independently and subsequently assembled into a complex.

Bacterial toxins exert their biological effects through several sequential stages: receptor binding, protoxin activation, endocytosis and Intracellular Transport, translocation of the catalytic fragment into the Cytosol, and action on the intracellular target.

Toxins typically bind to specific receptors On the surface of the target cell. For example, the receptor for diphtheria toxin is the heparin-binding epidermal growth factor precursor, whereas for cholera toxin, it is a specific ganglioside.

These receptors not only mediate the attachment of the toxin to The Cell surface but also participate in its subsequent transport to the intracellular target at various Stages of the process.

Following receptor binding, toxins generally undergo endocytosis and intracellular transport prior to membrane translocation into the cytosol to reach the intracellular target. Another potential mechanism involves retrograde transport via the secretory pathway—passing through endosomes and the Golgi apparatus to The Endoplasmic reticulum—followed by translocation across its membrane. Regardless of the specific endocytic pathway utilized for The transport of bacterial toxins, they may bypass the endosomal stage and reach their translocation site via alternative routes. For instance, to deliver the catalytic enzyme into the cell, a channel (pore) may form within the membrane, through which cytosol leakage can also occur.

Based on their MECHANISM OF ACTION, bacterial toxins are categorized into membrane-damaging agents (such as phospholipases, hemolysins, hyaluronidases, and collagenases) and those that act on intracellular targets. Examples of the latter include streptokinase from Streptococcus pyogenes, which hydrolyzes plasminogen, as well as clostridial collagenases.

Intracellular targets of bacterial toxins include G-Proteins, Actin, and Ribosomes. They are capable of catalyzing

specific biochemical reactions that result in the disruption of these intracellular targets (Table 2.2).

Class="center">Table 2.2

EFFECTS OF SELECTED BACTERIAL TOXins (after Pozur et al., 2003)

Overall, A wide variety of mechanisms exist by which bacterial toxins damage their target Cells.

Fungi. These organisms are capable of producing a vast array of toxins known as mycotoxins, some of which are listed in Table 2.3.

Mycotoxins produced by macrofungi (forming large fruiting bodies) likely serve as a defense mechanism against animals that might consume them prior to spore dispersal.

Toxic fungi that do not form large fruiting bodies (such as Aspergillus, Penicillium, and Fusarium) presumably protect not only themselves but also their food substrate from other consumers. Thus, they act as ecological chemoregulators. This plays a crucial role in the interactions between carnivorous fungi and nematodes. Nematodes can produce and release specific substances (nemins) that induce trap formation in carnivorous fungi. Conversely, the carnivorous fungi themselves secrete attractants that lure nematodes into their traps. Such substances include volatile Terpenes produced by Arthrobotrys oligospora and Candelabriella musiformis. In some fungal species, the same chemical acts as both an attractant and a toxin for nematodes, whereas in others, these Functions are performed by distinct compounds.

Table 2.3

EXAMPLES OF MYCOTOXINS (after Barbier, 1978 with additions)

The Biochemical Mechanisms of mycotoxin action are extremely diverse, encompassing the inhibition of various enzymes (including RNA polymerases), disruption of Protein Synthesis, and impairment of cellular Bioenergetics.

Among the substances produced and secreted by fungi, some exhibit antitumor activity. These include Polysaccharides (e.g., β-1,6-glucan from Grifola frondosa), certain alkaloids (such as agroclavine produced by Claviceps, several species of the genera Penicillium and Aspergillus, etc.).

At the same time, certain mycotoxins can induce oncological diseases. Such substances include aflatoxins (Fig. 2.9).

Certain symbiotic fungi, as well as bacteria and Yeasts inhabiting the Skin and dermal glands of mammals, contribute to The Development of their specific body odors, which play an important role in animal communication.

Algae and cyanobacteria. Unicellular algae and cyanobacteria are capable of synthesizing substances that are highly toxic to animals. Some of these are shown in Fig. 2.10.

Based on their effects on animals, algal toxins are classified into paralytic, diarrhetic, neurotoxic, and others.

Fig. 2.9. Structure of certain aflatoxins:

1 — aflatoxin B₂; 2 — sterigmatin; 3 — ochratoxins A (R=H, R₁=Cl), B (R=H, R₁=H), C (R=C₂H₅, R₁=Cl); 4 — aflatoxin G₁

Fig. 2.10. Substances toxic to vertebrates, produced

and secreted by algae:

1 — riprocephaelin from the green alga Rhipocephalus phoenix; 2 — brevetoxin B from the alga Ptychodiscus brevis; 3 — phosphohydrazidothioate from Ptychodiscus brevis; Ac — acetyl

The perennial brown algae Fucus vesiculosus and Ascophyllum nodosum produce chemical deterrents that repel the gastropod mollusk Littorina littorea, which acts as a consumer of these algae. These defensive compounds are polyphytols—low-molecular-weight phloroglucinol polymers.

Antagonistic interactions mediated by exometabolites can occur between algae and invertebrate animals. For instance, Water-soluble substances released by the sea anemone Condylactis gigantea inhibit the growth of green, red, and brown algae.

At the same time, A number of aquatic invertebrates (Mollusks, corals, sea anemones, etc.) form symbiotic associations with algae. For example, the sea anemone Anthopleura elegantissima, certain Tissues of the mollusk Tridacna crocea, and other organisms contain symbiotic algae with elevated levels of superoxide dismutase and catalase. These enzymes neutralize the excess oxygen produced by photosynthetic algae.

The quality and adequacy of the habitat, shaped by a combination of environmental factors, are of vital importance for the functioning and survival of living organisms.

In aquatic ecosystems, hydrobionts release a wide variety of Organic compounds into their habitat, leading to the accumulation of soluble forms. These substances may include compounds that disrupt the balance of oxidation-reduction processes in aquatic ecosystems. This occurs because hydrobionts, particularly algae, can release oxidizable soluble substances and antioxidants into the aquatic environment.

One of the consequences of the release of algal exometabolites into the aquatic environment is an increased concentration of hydrogen peroxide. It has also been established that certain algae, notably Westella botryoides, release cellular lipid extracts that exhibit antibacterial activity. Metabolites from various other algae (Table 2.4) and hydrobionts share similar properties.

The quality and suitability of the aquatic environment also depend on the composition and concentration of toxins released by hydrobionts, particularly algae.

Microorganisms are capable of secreting various chelators that can bind metals. On the one hand, this may lead to a micronutrient deficiency, while on the other hand, it can reduce the toxicity of anthropogenic pollution.

Other Aspects of metabolite accumulation in the habitat are also of great importance for hydrobionts, including those associated with the presence of enzymes, Vitamins, and various BIOLOGICALLY ACTIVE SUBSTANCES.

Table 2.4

EXAMPLES OF ANTIBACTERIAL SUBSTANCES PRODUCED AND SECRETED BY ALGAE (after Telitchenko and Ostroumov, 1990)

Soil microorganisms, much like aquatic ones, are also capable of producing and releasing bactericidal substances, toxins, and Other Compounds. Their vital activity likewise depends on the quality and adequacy of their habitat. A wide variety of toxins can be produced by cyanobacteria (Table 2.5).

Table 2.5

SOME CYANOBACTERIAL TOXINS

(after Telytchenko, Ostroumov, 1990)

It should be noted that the biochemical interaction of prokaryotes, fungi, and lower plants with other organisms likely promoted the adaptive response of these organisms and, consequently, an increase in the overall species diversity within these groups.