Michael J. Gault

Bio: Michael J. Gault is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Giardia lamblia & Small intestine. The author has an hindex of 5, co-authored 5 publications receiving 300 citations.

Encystation and expression of cyst antigens by Giardia lamblia in vitro

Abstract: The cyst form of Giardia lamblia is responsible for transmission of giardiasis, a common waterborne intestinal disease. In these studies, encystation of Giardia lamblia in vitro was demonstrated by morphologic, immunologic, and biochemical criteria. In the suckling mouse model, the jejunum was shown to be a major site of encystation of the parasite. Small intestinal factors were therefore tested as stimuli of encystation. An antiserum that reacted with cysts, but not with cultured trophozoites was raised in rabbits and used as a sensitive probe for differentiation in vitro. Cultured trophozoites that were exposed to bile salts showed a more than 20-fold increase in the number of oval, refractile cells that reacted strongly with anticyst antibodies, and in the expression of major cyst antigens. Exposure to primary bile salts resulted in higher levels of encystation than exposure to secondary bile salts. These studies will aid in understanding the differentiation of an important protozoan pathogen.

Biliary lipids support serum-free growth of Giardia lamblia.

Abstract: Giardia lamblia has been grown in vitro only in media containing serum or serum fractions How this pathogen can grow in the human small intestinal lumen without serum is not known We found that samples of human hepatic or gall bladder bile maintained G lamblia survival for 24 to 48 h in medium without serum but did not support growth By contrast, an artificial biliary lipid dispersion containing six bile salts, phosphatidylcholine (PC), and cholesterol, in the ratios characteristic of human bile, supported parasite growth in medium without serum or serum fractions To define the requirements, we showed that 1-palmitoyl-2-linoleoyl-PC or 1-palmitoyl-2-oleoyl-PC (which predominate in human bile) satisfied the requirement for PC Moreover, either glycocholate or glycodeoxycholate could be substituted for the bile salt mixture The finding that biliary lipids can support serum-free growth of G lamblia may help explain why this parasite colonizes the upper small intestine

Cholate-dependent killing of Giardia lamblia by human milk.

Abstract: We showed previously that nonimmune human milk (NHM) kills Giardia lamblia trophozoites in vitro and presented evidence that killing requires the bile salt-stimulated lipase of milk. Since this enzyme is activated by bile salts, killing should be dependent on the presence of bile salts. We now show that killing by fresh NHM or NHM stored at -70 degrees C is totally dependent on sodium cholate (a bile salt). With less than 0.4 mM cholate, no parasites were killed, whereas with 1 mM cholate, greater than 99.7% were killed by 5% NHM in 30 min. Moreover, killing activity was completely heat labile. The G. lamblia-killing activity of human milk was greatly altered by storage at -10 or -20 degrees C. In less than 23 days, the 50% lethal dose decreased, cholate dependence was lost, and killing activity became heat stable. In contrast, the activity of milk stored at -70 degrees C remained unchanged. Milk lipase activity, like killing activity, became cholate independent during storage at -10 or -20 degrees C. On the basis of these results, we hypothesize that killing of G. lamblia by fresh NHM or NHM stored at -70 degrees C depends on bile salt-stimulated lipase, which must be activated by bile salts. In contrast, NHM stored at -20 degrees C accumulated free fatty acids which kill G. lamblia. In support of this thesis, milk stored at -10 degrees C had a concentration of 18.7 mM free fatty acids compared with only 1.1 mM in an identical sample stored at -70 degrees C.

Tolerance of axenically cultured Entamoeba histolytica and Giardia lamblia to a variety of antimicrobial agents

Abstract: Twelve antimicrobial agents were tested for use in axenic cultures of Entamoeba histolytica and Giardia lamblia. Ten did not inhibit parasite growth at concentrations of at least two-fold above the effective antibacterial or antifungal levels. We have found the combination of piperacillin (500 μg/ml) plus amikacin (125 (μ/ml) to be useful in (i) axenization of a new strain of E. histolytica, (ii) eradication of multiply drug-resistant contaminants in cultures and (iii) prevention of bacterial growth in experiments with non-sterile components.

Foam structures with a negative poisson's ratio

Abstract: A novel foam structure is presented, which exhibits a negative Poisson's ratio. Such a material expands laterally when stretched, in contrast to ordinary materials.

Biology of Giardia lamblia.

Abstract: Giardia lamblia is a common cause of diarrhea in humans and other mammals throughout the world. It can be distinguished from other Giardia species by light or electron microscopy. The two major genotypes of G. lamblia that infect humans are so different genetically and biologically that they may warrant separate species or subspecies designations. Trophozoites have nuclei and a well-developed cytoskeleton but lack mitochondria, peroxisomes, and the components of oxidative phosphorylation. They have an endomembrane system with at least some characteristics of the Golgi complex and encoplasmic reticulum, which becomes more extensive in encysting organisms. The primitive nature of the organelles and metabolism, as well as small-subunit rRNA phylogeny, has led to the proposal that Giardia spp. are among the most primitive eukaryotes. G. lamblia probably has a ploidy of 4 and a genome size of approximately 10 to 12 Mb divided among five chromosomes. Most genes have short 5′ and 3′ untranslated regions and promoter regions that are near the initiation codon. Trophozoites exhibit antigenic variation of an extensive repertoire of cysteine-rich variant-specific surface proteins. Expression is allele specific, and changes in expression from one vsp gene to another have not been associated with sequence alterations or gene rearrangements. The Giardia genome project promises to greatly increase our understanding of this interesting and enigmatic organism.

Drug targets and mechanisms of resistance in the anaerobic protozoa

Abstract: The anaerobic protozoa Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica infect up to a billion people each year. G. duodenalis and E. histolytica are primarily pathogens of the intestinal tract, although E. histolytica can form abscesses and invade other organs, where it can be fatal if left untreated. T. vaginalis infection is a sexually transmitted infection causing vaginitis and acute inflammatory disease of the genital mucosa. T. vaginalis has also been reported in the urinary tract, fallopian tubes, and pelvis and can cause pneumonia, bronchitis, and oral lesions. Respiratory infections can be acquired perinatally. T. vaginalis infections have been associated with preterm delivery, low birth weight, and increased mortality as well as predisposing to human immunodeficiency virus infection, AIDS, and cervical cancer. All three organisms lack mitochondria and are susceptible to the nitroimidazole metronidazole because of similar low-redox-potential anaerobic metabolic pathways. Resistance to metronidazole and other drugs has been observed clinically and in the laboratory. Laboratory studies have identified the enzyme that activates metronidazole, pyruvate:ferredoxin oxidoreductase, to its nitroso form and distinct mechanisms of decreasing drug susceptibility that are induced in each organism. Although the nitroimidazoles have been the drug family of choice for treating the anaerobic protozoa, G. duodenalis is less susceptible to other antiparasitic drugs, such as furazolidone, albendazole, and quinacrine. Resistance has been demonstrated for each agent, and the mechanism of resistance has been investigated. Metronidazole resistance in T. vaginalis is well documented, and the principal mechanisms have been defined. Bypass metabolism, such as alternative oxidoreductases, have been discovered in both organisms. Aerobic versus anaerobic resistance in T. vaginalis is discussed. Mechanisms of metronidazole resistance in E. histolytica have recently been investigated using laboratory-induced resistant isolates. Instead of downregulation of the pyruvate:ferredoxin oxidoreductase and ferredoxin pathway as seen in G. duodenalis and T. vaginalis, E. histolytica induces oxidative stress mechanisms, including superoxide dismutase and peroxiredoxin. The review examines the value of investigating both clinical and laboratory-induced syngeneic drug-resistant isolates and dissection of the complementary data obtained. Comparison of resistance mechanisms in anaerobic bacteria and the parasitic protozoa is discussed as well as the value of studies of the epidemiology of resistance.

Immune Response to Giardia duodenalis

Abstract: The intestinal protozoan Giardia duodenalis is a widespread opportunistic parasite of humans and animals. This parasite inhabits the upper part of the small intestine and has a direct life cycle. After ingestion of cysts, which are the infective stage, the trophozoites emerge from the cysts in the duodenum and attach to the small intestinal mucosa of the host. Since the migration of trophozoites from the lumen of the intestine into surrounding tissues is an unusual occurrence, the immune response to Giardia remains localized. The identification of antigens that play a role in acquired immunity has been difficult because of the occurrence of antigenic variation and because, Giardia being an ubiquituous organism, it is possible that the antigenic profiles of isolates from different geographic areas will vary. Innate-immunity mechanisms play a role in the control and/or severity of the infection. Both humoral and cell-mediated immune responses play a role in acquired immunity, but the mechanisms involved are unknown. A variety of serological assays have been used to detect circulating antibodies in serum. Because of the biological characteristics of the parasite and the lack of suitable antigens, the sensitivity of serological assays remains poor. On the other hand, detection of antigens in feces of infected patients has met with success. Commercial kits are available, and they are reported to be more sensitive than microscopic examination for the detection of giardiasis on a single specimen.

Giardia and Giardiasis

Abstract: It is over 10 years since Meyer and Radulescu (1979) reviewed Giardia and giardiasis in Advances in Parasitology. In their introduction, they emphasized that "despite their ubiquity and antiquity, the Giardia have, until recently, been little studied". In the intervening years, Giardia has been extensively studied. The number of papers published has increased enormously, two books on the parasite have been produced (Erlandsen and Meyer, 1984; Meyer, 1990a), and an international conference on Giardia has been organized (Wallis and Hammond, 1988). Yet it is still very difficult to keep up with developments in this productive field of research and, despite all these research efforts, several fundamental questions concerning Giardia and giardiasis remain unresolved (Table 1), particularly with respect to the relationship of Giardia and disease, and the role of zoonotic transmission. Indeed, it is only recently that we have started to appreciate the clinical significance of Giardia infections in developing countries and among disadvantaged groups. Giardia is now recognized as one of the 10 major parasites of humans, being equal to ascariasis as a cause of death in the developing world (Warren, 1989; Meyer, 1990b). In developed countries, Giardia has the distinction of being the most commonly reported human intestinal parasite (Acha and Szyfres, 1987; Thompson et al., 1990a; Schantz, 1991). Regrettably, however, the range of drugs available to treat giardiasis is limited and their efficacy leaves much to be desired. There is an urgent need for new antigiardial agents, yet this search is hampered by our lack of understanding of many fundamental aspects of Giardia biochemistry and metabolism. In addition, although the application of molecular biological techniques to research on Giardia has revealed new avenues of investigation, it has also given rise to many new questions about this intriguing organism concerning its phylogenetic position, reproductive behaviour and genetic diversity. To review Giardia and giardiasis in detail would require at least an entire volume of Advances in Parasitology. Such treatment in depth is not warranted at this time in view of the excellent book recently edited by Meyer (1990a). Our intention here is to give an up-to-date overview of Giardia and giardiasis and provide an insight into the enormous wealth of literature on the subject, as well as highlight the most important recent developments and unresolved questions.