The differential permeability of cell membranes to various electrolytes and non-electrolytes represents one of the most fundamental characteristics of life. In the context of parasitology, differences in transport properties when parasite and host cells are compared represent an important avenue for chemotherapy. For example, a recent success in this area exploits the difference in nucleoside transport systems between host and parasite to produce combination therapy of Schistosoma japonicum by tubercidin and nitrobenzylthioinosine-5′-monophosphate (Elkouni, Diop & Cha, 1983). The morning session of this symposium was devoted to various aspects of membrane structure and function, particularly in the context of characterizing parasite transport systems. It is therefore probably worth while to present a simple classification of membrane transport systems, based on their complexity, and energy requirements. Table 1 summarizes the principal types of transport to be considered, starting with simple (Stokesian) diffusion. This will depend on permeant size, charge and lipid solubility. Classically, transmembrane transport of such molecules as aliphatic alcohols, ureas and small sugars has been studied, in simple systems such as the red cell (see Stein (1986) for references). In fact this route is important for intracellular delivery of a variety of hydrophobic molecules, for example phenylalanine benzyl ester transport as an antisickling agent (Acquaye, Young, Ellory, Grecki & Wilchek, 1983), or quin-2 and fura-2 for intracellular calcium measurements (Tsien, 1981).

The consensus view of biomembrane structure is outlined. The present model is built upon a fluid lipid matrix, usually two molecules in length, into which the proteins are embedded. The lipid bilayer organization is discussed, such as their phase transition and fluid character and the effect of cholesterol upon the chain organization. The non-lamellar arrangement which some lipids adopt is described. The use of new physical techniques for obtaining information about the structure and dynamics of membrane proteins are described. These techniques include electron diffraction, electron microscopy and FTIR spectroscopy. Models of the structures of the Ca2+–ATPase and the glucose transporter from erythrocytes are shown, indicating the putative helices embedded in the lipid bilayer and the groups of amino acids in the aqueous environment. These models are based upon biochemical methods to obtain amino acid sequences using DNA cloning techniques. Finally, an experimental method using triplet probes is described for the study of the rotational dynamics of membrane proteins. Labelled monoclonal antibodies for studying the dynamics of the glucose transporter have been used.

Many clinically useful antibacterial drugs have intracellular target sites. Therefore, in order to reach their targets, these compounds must be able to cross bacterial outer and cytoplasmic membranes. Considerable information is available on the mechanisms by which antibiotics cross bacterial membranes and, in many cases, it is now possible to define the molecular basis of their uptake. Passage of drugs across the outer membrane of Gram-negative bacteria can occur by diffusion through porin channels (e.g. β-lactams and tetracyclines), by facilitated diffusion using specific carriers (e.g. albomycin), or by self-promoted uptake (e.g. aminoglycosides and polymyxins). Transfer of antibiotics across the bacterial cytoplasmic membrane is usually mediated by active, carrier-mediated, transport systems normally operating to transport essential solutes into the cell. For example, the antibiotic streptozotocin bears sufficient structural resemblance to N-acetyl-D-glucosamine to be transported by the phosphoenolpyruvate : phosphotransferase system, and D-cycloserine is recognized by the D-alanine, proton motive force dependent transport system. However, in some cases (e.g. tetracycline) although carrier-mediated transport is implied by the observation that drug uptake is energy dependent, the nature of the membrane carrier(s) responsible is unknown. Knowledge acquired from studies on bacterial peptide transport has been successfully used to deliver (or smuggle) amino acid mimetics disguised as peptides into the bacterial cell. These amino acid mimetics, although often poorly transported in their own right, are frequently potent inhibitors of bacterial peptidoglycan or lipopolysaccharide synthesis once they have gained access to the interior of the cell.

This essay deals in turn with the six main mechanisms that are believed to be involved in the passage of small molecules across the cell membrane of yeasts and fungi. Such solutes include amino acids, carbohydrates, purines and pyrimidines and other nutrients, among which are the ions K+, , or . The subject has been reviewed extensively (see, for example, Eddy, 1982; Cooper, 1982; Serrano, 1984; Harold, 1986). Transport systems relate to chemotherapy in two ways. First, they may themselves be potential targets for drug action. Second, they may deliver a drug to its intracellular target, the drug being an illicit passenger in a transport system with a different primary role. Most of our knowledge about yeast and fungal transport is currently based on studies with relatively few species selected because they are known to be amenable to genetic and biochemical analysis. The organisms include representative strains of Neurospora crassa or of Saccharomyces cerevisiae and selected species of Rhodotorula and Schizosaccharomyces. Fungal organisms pathogenic to man, such as Candida albicans, those causing either systemic fungal infections (see Kerridge, 1986; Shepherd, Poulter & Sullivan, 1985), or the numerous fungal diseases of plants have been little used as models of nutrient transport, despite their clinical or economic importance. Whether all these ecologically diverse organisms, which in evolutionary terms are only distantly related, employ only the transport mechanisms so far discovered in Saccharomyces cerevisiae is an open question.

The asexual stages of Plasmodium living within the erythrocyte result in growth-related changes in the permeability properties of the red cell for substances such as glucose, amino acids, purine nucleosides, sodium, potassium, calcium, zinc, iron and several antimalarial drugs such as chloroquine, amodiaquine and mefloquine. In most cases such changes do not appear to be due to a modification in the affinity or specificity of red cell transporters; indeed, for most substances the membrane-associated transporters are either unaffected or are partially inactivated. In malaria-infected erythrocytes, where a striking increase in influx has been observed, it has been attributed to the insertion of parasite-encoded transporters into the red cell membrane or the formation of aqueous leaks and/or pores. Leak formation, in the vast majority of cases, does not appear to be dependent on the insertion of plasmodial proteins into the red cell membrane. However, since the data presently available are less than satisfactory for discriminating amongst the various possible transport mechanisms future studies will require painstaking efforts and carefully controlled conditions to discriminate amongst the various transport systems which are operational in the malaria-infected red cell and the parasite.

During their life-cycle many parasites experience a wide range of environments including free living and those provided by a variety of intermediate and final hosts. The nutritional requirements of parasites are met by physiological processes adapted to exploit the physico-chemical characteristics provided by different hosts. In helminth parasites these adaptations are frequently expressed on the tegumentary surface. As an example of adaptations within the Trematoda, the control of monosaccharide transport in Proterometra sp. is described. Environmental sodium, although not directly involved in the uptake process, nevertheless regulates the expression of transport capabilities. In the Cestoda, the uptake of monosaccharides and amino acids is described for Hymenolepis diminuta. The metacestode of this tapeworm inhabits the blood system of an arthropod, and the adult the gut of a mammal. There are quantitative and qualitative differences in the amino acids and monosaccharides in these two environments and these are reflected in the transport mechanisms exhibited by the two forms of the life-cycle. In Echinococcus granulosus the transfer of amino acids, sugars and macromolecules across the membranes of hydatid cysts and protoscoleces is described. The major difference between these two stages in the life-cycle relates to the ability of hydatid cysts to absorb macromolecules, whereas protoscoleces are impermeable to these compounds. The potential for future work is emphasized.

Several major groups of parasitic helminths (Monogenea, Digenea and Nematoda) possess two surfaces that are potentially absorptive in nature. These are an external surface, a tegument in the platyhelminths and cuticle in the nematodes, and the intestine. This paper discusses the relative contributions of these absorptive surfaces in the nutrition of these parasitic helminths. There are many factors that determine the availability of, and a parasite's ability to absorb nutrients via either of these surfaces, and this review discusses individually some of the more important morphological, physiological and environmental factors affecting the potential nutritional roles of these surfaces. It is clear from such a summary of previous studies that the intestines and teguments (cuticles) of helminth parasites can each serve an important nutritional role. However, insufficient data make it impossible at this time to determine the relative nutritional roles of these surfaces in any single parasitic helminth.

Parasitic helminths excrete or secrete (ES) a variety of molecules into their mammalian hosts. The effects of these ES products on the host's immune responses are reviewed. Investigations into the source of antigenic or immunoregulatory ES products have identified the cuticular and tegumental surfaces of some nematodes and trematodes respectively as being important sources of ES products; other ES molecules are released through specialized excretory or secretory organs. It is proposed that the active shedding of surface antigens may serve as an important source of parasite antigens available to the immune system in a form in which they can be taken up and processed by antigen-presenting dendritic cells, macro-phages and certain B cells for presentation to T helper cells. The ES products of nematodes, trematodes and cestodes contribute to immune evasion strategies of the parasites through mechanisms including shedding of surface-bound ligands and cells, alteration of lymphocyte, macrophage and granulocyte functions and modulation of complement and other host inflammatory responses. Immunopathology may be induced by ES products as in the development of granulomas around entrapped schistosome eggs. In some host – parasite systems ES antigens may induce host-protective immune responses and this source of protective antigens has been utilized in the successful vaccination against helminth infections, particularly against infection with trichurid nematodes and the metacestode stage of cestode parasites. The use of ES antigens in immunodiagnosis of helminth infection is also briefly discussed.

The interrelationships between drugs and parasite surfaces are considered under the headings of (a) effects on membrane transport, (b) drug uptake mechanisms and (c) effects on surface morphology and function: praziquantel is discussed under a separate heading. The range of chemotherapeutic compounds that cause permeability changes and concomitant morphological disruption is discussed in terms of mode of drug action. Interpretation of the available data renders it difficult to identify the primary mode of action in the drugs considered. Drug uptake mechanisms are known for relatively few compounds; drug resistance as a function of drug acquisition is discussed. The role of the parasite surface as a specific drug target is argued.