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PURPOSE OF REVIEW: Environmental fungi such as Cryptococcus neoformans and Aspergillus fumigatus must survive many different and changing environments as they transition from their environmental niches to human lungs and other organs. Fungi alter their cell surfaces and secreted macromolecules to respond to and manipulate their surroundings. RECENT FINDINGS: This review focuses on exo-polysaccharides, chains of sugars that transported out of the cell and spread to the local environment. Major exo-polysaccharides for C. neoformans and A. fumigatus are glucuronylxylomannan (GXM) and galactosaminogalactan (GAG), respectively, which accumulate at high concentrations in growth medium and infected patients SUMMARY: Here we discuss GXM and GAG synthesis and export, their immunomodulatory properties, and their roles in biofilm formation. We also propose areas of future research to address outstanding questions in the field that could facilitate development of new disease treatments.

SUMMARYEnvironmental pathogens, which move from ecological niches to mammalian hosts, must adapt to dramatically different environments. Microbes that disseminate farther, including the fungal meningitis pathogen Cryptococcus neoformans, require additional adaptation to diverse tissues. When C. neoformans enters the lungs, infecting cells (30 μm diameter), then form a heterogeneous population. The brain contains uniformly small cells (∼7 μm). We demonstrate that formation of a small C. neoformans morphotype – called “seed” cells due to their disseminating ability – is critical for extrapulmonary organ entry. Seed cell formation is triggered by environmental factors, including C. neoformans’ environmental niche, pigeon guano. The underlying trigger, phosphate, can be released by tissue damage, potentially establishing a feed-forward loop of seed cell formation and dissemination. We demonstrate that C. neoformans’ size variation is not just a continuum but inducible subpopulations that change host interactions to facilitate microbe survival and spread.

The commensal microbiota has an important impact on host health, which is only beginning to be elucidated. Despite the presence of fungal, archaeal, and viral members, most studies have focused solely on the bacterial microbiota. Antibodies against the yeast Saccharomyces cerevisiae are found in some patients with Crohn’s disease (CD), suggesting that the mycobiota may contribute to disease severity. We report that S. cerevisiae exacerbated intestinal disease in a mouse model of colitis and increased gut barrier permeability. Transcriptome analysis of colon tissue from germ-free mice inoculated with S. cerevisiae or another fungus, Rhodotorula aurantiaca, revealed that S. cerevisiae colonization affected the intestinal barrier and host metabolism. A fecal metabolomics screen of germ-free animals demonstrated that S. cerevisiae colonization enhanced host purine metabolism, leading to an increase in uric acid production. Treatment with uric acid alone worsened disease and increased gut permeability. Allopurinol, a clinical drug used to reduce uric acid, ameliorated colitis induced by S. cerevisiae in mice. In addition, we found a positive correlation between elevated uric acid and anti-yeast antibodies in human sera. Thus, yeast in the gut may be able to potentiate metabolite production that negatively affects the course of inflammatory bowel disease.

The aflatoxin biosynthetic pathway represents one of the est studied pathways of fungal secondary metabolism. Its lucidation is the result of over 30 years of study by cientists in many disciplines. For recent reviews on the hemistry of the pathway see articles by Bhatnagar et al. 1992) Minto and Townsend (1997), and Woloshuk and rieto (1997). Concern over the toxicity and carcinogenicty of aflatoxin has been the prime force driving research in his area. Aflatoxin B1 (AFB1) is the most potent naturally ccurring carcinogen known (Squire, 1989), and epidemioogical data implicate aflatoxin as a component of liver ancer in humans in certain parts of the world (Hall and ild, 1994). Although aflatoxins are not extremely toxic, onsumption of aflatoxin contaminated food by animals can ead to decreased weight gain, hemorrhaging, and suppression f the immune system (Miller and Wilson, 1994). Aflatoxins are produced by four species of Aspergillus: . flavus, A. parasiticus, A. nomius, and A. tamarii (Payne, 998; Kurtzman et al., 1986; Goto et al., 1996). From an gricultural standpoint, the two most significant fungi are

Four bacteriophages (phages) growing on the same Leuconostoc strain were characterised. Electron micrographs showed these phages to be similar in morphology to the commonly isolated lactococcal phages with head diameters ranging from 49–55 nm and tail lengths of 117–131 nm. A distinctive base plate and collar were also present. From restriction enzyme analysis of purified phage DNA, the genome sizes were 23–29 kb. All four phages showed one major structural protein (of approximately 24 kDa) on SDS polyacrylamide gels. Hybridization experiments confirmed that the phages belonged to the same homology group. There was no homology between DNA from these phages and DNA from a prolate or small isometric lactococcal phage.

This paper reports on the application of the ligase chain reaction (LCR) to the specific detection of variants of the nisin structural gene (nisinA and nisinZ) in nisin producing strains of Lactococcus lactis ssp lactis. The LCR assay was used to screen nisin producing strains to determine which form of the nisin structural gene they contained. This method of differentiating the nisin structural gene variants provides a useful alternative to the only other available genetic differentiation, that of sequencing the gene.

The Durham route to polyacetylene provides, for the first time, the possibility of controlling the crystalline structure of this fascinating material. This control will enable us to probe the role of the redox doping and relative spatial co-ordinates of the chains in determining electrical conductivity. Before this can be accomplished it is necessary to understand the nature of the order within the variety of materials which can now be produced. Material produced from quiescent films can have a range of structures from largely amorphous (inasmuch as a structure composed of rigid rods can exhibit disorder) to slightly crystalline. By stretching the precursor film during transformation highly oriented, crystalline polyacetylene can be produced. This offers a range of structures and should enable the separation of inter- and intra-chain electronic effects for the first time.

The structure of polyacetylene produced from a precursor polymer is compared with that of polymer produced by a soluble Ziegler-Natta catalyst. X-ray diffraction shows that the precursor polyacetylene can be produced with a wide range of ordering from apparently amorphous to crystalline, although the ordering is never as high as that of polymer produced by the Ziegler-Natta route. An increase in ordering, as measured by X-ray peak width, has been observed during isomerization; this contrasts with normal polyacetylene where no change in order is found. Both forms of polyacetylene show a gradual shift in the interchain d -spacing from 395 pm ( cis/trans mixed) to 365 pm ( trans ). Since only a single peak is found in this region the cis - and trans -forms are not phase-separated on a scale of 3 nm or more. Small-angle X-ray scattering also indicates that discrete crystalline and amorphous regions, as found in polyethylene, are not present

The processes involved in the thermal transformation of ‘Durham polyacetylene precursor’, poly[[5,6-bis(trifluoromethyl)-bicyclo[2,2,2]octa-5,7-diene-2,3-diyl]-1,2-ethenediyl], to all- trans polyacetylene have been studied. Above about 100°C the reactions are virtually concurrent, but at 50°C one can distinguish a first-order elimination ( k = 7.6 × 10 −4 s −1 ), effusion of the elimination product ( D = 4 × 10 −9 cm 2 s −1 ), and a first order cis-trans isomerization ( k = 1.5 × 10 −5 s −1 ). The isomerization is very sensitive to traces of oxygen below 80°C, but at higher temperatures this is less pronounced and the reaction becomes approximately second order. Isomerization is generally more facile in the less ordered Durham polymer than in polymers from the Shirakawa route.

Mechanistic aspects of the two step Durham route to polyacetylene are discussed. It is shown that a catalyst based on MoCl5 gives a higher proportion of cis vinylenes in both precursor polymer and nascent polyacetylene than does a WC16 based system.

Polyacetylene prepared by the Shirakawa route is a mat of crystalline fibrills, which are capable of being oxidized or reduced to a highly conducting state. Polyacetylene can also be produced from a soluble precursor polymer by a thermally driven transformation reaction (the ‘Durham’ route) as a solid, coherent film. This transformation consists of the elimination of a substituted benzene unit followed by the isomerization of the largely cis polyacetylene produced to a disordered trans isomer. We have studied the effect of different transformation conditions and from these studies it is possible to gain an insight into these processes. Techniques such as caloremetry, infrared, resonance Raman and optical spectroscopy, e.s.r., X-ray diffraction and electrical conductivity have all been used to probe the transformation and the product. The resultant information gives a consistent picture of the overall transformation processes detailed above but also shows an ordering associated with higher transformation temperatures. A thorough knowledge of these processes enables the orientation of the precursor to produce highly crystalline material.