Ionophores: their use as ruminant growth promotants and impact on food safety

Ionophores (such as monensin, lasalocid, laidlomycin, salinomycin and narasin) are antimicrobial compounds that are commonly fed to ruminant animals to improve feed efficiency. These antimicrobials specifically target the ruminal bacterial population and alter the microbial ecology of the intestinal microbial consortium, resulting in increased carbon and nitrogen retention by the animal, increasing production efficiency. Ionophores transport ions across cell membranes of susceptible bacteria, dissipating ion gradients and uncoupling energy expenditures from growth, killing these bacteria. Not all bacteria are susceptible to ionophores, and several species have been shown to develop several mechanisms of ionophore resistance. The prophylactic use of antimicrobials as growth promotants in food animals has fallen under greater scrutiny due to fears of the spread of antibiotic resistance. Because of the complexity and high degree of specificity of ionophore resistance, it appears that ionophores do not contribute to the development of antibiotic resistance to important human drugs. Therefore it appears that ionophores will continue to play a significant role in improving the efficiency of animal production in the future.     

Chitosan as antimicrobial agent: applications and mode of action

Chitosan, a hydrophilic biopolymer industrially obtained by N-deacetylation of chitin, can be applied as an antimicrobial agent. The current review of 129 references describes the biological activity of several chitosan derivatives and the modes of action that have been postulated in the literature. It highlights the applications of chitosan as an antimicrobial agent against fungi, bacteria, and viruses and as an elicitor of plant defense mechanisms.     

Surface films as mosquito larvicides: partitioning the mode of action

Oils and other surface films used against mosquito larvae may act by flooding the tracheal system with oil, by disrupting the surface forces that allow larvae to rest at the surface, by toxicity, or by eliciting chemosensory responses. In an attempt to identify diagnostic symptoms of these modes of action we treated fourth-stage larvae of Culex pipiens L. form molestusForskål (Diptera: Culicidae: Culicinae) with agents operating in a single mode (Ondina oil for flooding with oil, nicotine for toxicity, and the detergent Triton X-100 for disruption of surface forces), in two modes (silicone oil) or in three (eucalyptus oil, citronellal, or caproic acid ethyl ester). We monitored the time course of flooding and immobilisation, used experiments to separate volatile toxicity from toxicity of the aqueous solution, and used video and The Observer software to analyse larval behaviour.Larvae that experienced tracheal flooding applied their mouthparts to the siphon (tail nibbling), often losing contact with the surface while doing so and falling to the bottom. Nicotine immobilised larvae without interfering with surface forces, and the larvae remained immobile hanging from the air-water interface for long periods. In detergent, larvae made repeated unsuccessful attempts to thrust the siphon through the surface. The behaviour-modifying chemicals caproic acid ethyl ester, eucalyptus oil and citronellal all operated in more than one mode. They all decreased the proportion of time larvae spent at the surface, whereas Ondina oil and silicone fluid increased it.Using this approach it should be possible to identify the modes of action of novel larvicidal agents. This could form a basis for rational design of larvicides giving an optimal compromise between efficacy against mosquito larvae and minimal damage to non-target organisms.     

Improved health and growth of fish fed mannan oligosaccharides: Potential mode of action

Nowadays, aquaculture industry still confronts several disease-related problems mainly caused by viruses, bacteria and parasites. In the last decade, the use of mannan oligosaccharides (MOS) in fish production has received increased attention due to its beneficial effects on fish performance and disease resistance. This review shows the MOS use in aquaculture with a specific emphasis on the effectiveness of the several MOS forms available in the market related to disease resistance, fish nutrition and the possible mechanisms involved. Among the main beneficial effects attributed to MOS dietary supplementation, enhanced fish performance, feed efficiency and pathogen protection by potentiation of the systemic and local immune system and the reinforcement of the epithelial barrier structure and functionality are some of the most commonly demonstrated benefits. These combined effects suggest that the reinforcement of the intestinal integrity and functionality, together with the stimulation of the innate immune system, are the primary mode of action of MOS in fish. However, the supplementation strategy related to the structure of the MOS added, the correct dose and duration, as well as fish species, size and culture conditions are determinant factors to achieve improvements in health status and growth performance.     

Bt: mode of action and use

The insecticidal toxins from Bacillus thuringiensis (Bt) represent a class of biopesticides that are attractive alternatives to broad-spectrum "hard" chemistries. The U.S. Food Quality Protection Act and the European Economic Council directives aimed at reducing the use of carbamate and organophosphate insecticides were expected to increase the use of narrowly targeted, "soft" compounds like Bt. Here we summarize the unique mode of action of Bt, which contributes to pest selectivity. We also review the patterns of Bt use in general agriculture and in specific niche markets. Despite continued predictions of dramatic growth for biopesticides due to US Food Quality Protection Act-induced cancellations of older insecticides, Bt use has remained relatively constant, even in niche markets where Bt has traditionally been relatively high.     

The mode of action of nerve growth factor in PC12 cells

This review deals with the mechanism of nerve growth factor action. In view of the many and diversified effects of this growth factor, and since it could utilize different mechanism(s) in distinct types of cells, we have confined our analysis to the best characterized and more extensively studied target, the clonal cell line PC12. When exposed to NGF in vitro, these neoplastic cells recapitulate the last major steps of neuronal differentiation, i.e., the commitment to become a neuron and the acquisition of the neuronal phenotype. This is characterized by electrically excitable neurites, a display of a highly organized cytoskeleton, and the specific chemical and molecular neuronal properties. These effects are elicited upon the interaction of NGF with a receptor whose gene has been cloned and whose kinetic properties are now relatively well characterized. It is not yet clear, on the contrary, if and which of the several potential second messengers (cAMP, Ca, or phosphoinositides) that undergo marked fluctuations following NGF binding, transduce and amplify the NGF message. Among both the early and late effects of NGF is the modulation of expression of several genes. Some of the products of these genes are mainly restricted to nerve cells and others appear to play a crucial role in regulating the proper assembly of cytoskeletal elements. It is hypothesized that this complex array of chemical, molecular, and ultrastructural changes is triggered by NGF, not through activation of a single pathway, but more likely via combinatorial processes whereby several intracellular signals interplay before the irreversible commitment of becoming a neuron is undertaken.     

Pyrrolidinedione derivatives as antibacterial agents with a novel mode of action

The pseudopeptide pyrrolidinedione natural products moiramide B and andrimid represent a new class of antibiotics that target bacterial fatty acid biosynthesis. Structure-activity relationship (SAR) studies revealed a high degree of variability for the fatty acid side chain, allowing optimization of physicochemical parameters, and a restricted SAR for the pyrrolidinedione group, indicating major relevance of this subunit for efficient target binding.     

Flavonols and fertilization in Petunia hybrida: localization and mode of action during pollen tube growth

Flavonols form an important class of flavonoids which serve an essential function during plant reproduction. Flavonoid biosynthesis is initiated by the enzyme chalcone synthase (CHS). A high abundance of flavonols and chs mRNA was demonstrated in male and female reproductive organs of Petunia hybrida. Detailed analyses revealed precise spatial and temporal regulation of the chs promoter and flavonol synthesis in the stigma, style and ovules. Transgenic plants were generated with a complete block of flavonol biosynthesis as the result of anti-sense inhibition of chs gene activity. The absence of flavonols by this dominant mutation rendered these plants self-sterile. Pollination experiments with wild-type and mutant plants revealed that the production of flavonols in either the anthers or the pistils was required for pollen tube growth and seed set. Mutant pollen without flavonols in their exine germinated normally. However, after a short period of in vitro pollen tube growth the tips of these tubes disrupted and the protoplasm was disloaded leading to the death of the pollen grain. Addition of flavonol aglycones but not other flavonoids complemented this phenotype. Confocal laser scanning microscopy revealed the localization of high levels of flavonols throughout the wild-type pollen tube. These compounds were not detected in the exine or cell wall of growing tubes. In addition, it was observed that the flavone apigenin could completely inhibit pollen tube growth. Taken together, it is shown that flavonols play an important role in the growth of the pollen tube and their mode of action is discussed.     

Understanding the mode of action of L-nucleosides as antiviral agents: a molecular modeling approach

Computer modeling studies have been performed on the several pairs of D- and L-nucleoside inhibitors with the HIV-1 RT model. Additionally, clinically important M184V mutation, which confers the viral resistance against 3TC and FTC, were studied by the same modeling system.