Contact-induced apical asymmetry drives the thigmotropic responses of Candida albicans hyphae

Acknowledgements We thank Marco Thiel for assistance with data interpretation, Peter Sudbery for the provision of strains and Jeremy Craven for useful discussions. This work was supported by a BBSRC-DTG to D. D. T., NIH award DK083592 to F. J. B. and P. A. J., and a Royal Society URF UF080611 and MRC NIRG 90671 to A. C. B.Non peer reviewedPublisher PD

Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen

The survival of all microbes depends upon their ability to respond to environmental challenges. To establish infection, pathogens such as Candida albicans must mount effective stress responses to counter host defences while adapting to dynamic changes in nutrient status within host niches. Studies of C. albicans stress adaptation have generally been performed on glucose-grown cells, leaving the effects of alternative carbon sources upon stress resistance largely unexplored. We have shown that growth on alternative carbon sources, such as lactate, strongly influence the resistance of C. albicans to antifungal drugs, osmotic and cell wall stresses. Similar trends were observed in clinical isolates and other pathogenic Candida species. The increased stress resistance of C. albicans was not dependent on key stress (Hog1) and cell integrity (Mkc1) signalling pathways. Instead, increased stress resistance was promoted by major changes in the architecture and biophysical properties of the cell wall. Glucose- and lactate-grown cells displayed significant differences in cell wall mass, ultrastructure, elasticity and adhesion. Changes in carbon source also altered the virulence of C. albicans in models of systemic candidiasis and vaginitis, confirming the importance of alternative carbon sources within host niches during C. albicans infection

Multi trace element profiling in pathogenic and non-pathogenic fungi

Acknowledgements SW and EM were funded by an MRC NIRG to AB (G0900211/90671). AP was funded by a British Mycological Society Summer Studentship. AB was funded by a Royal Society URF (UF080611) and a Senior Wellcome Research Fellowship (206412/A/17/Z), which also funded TB. DW was funded by a Senior Wellcome Research Fellowship (214317/A/18/Z). The work was carried out in the MRC Centre for Medical Mycology (MR/N006364/2). This article is part of the Fungal Adaptation to Hostile Challenges special issue for the third International Symposium on Fungal Stress (ISFUS), which is supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo grant 2018/20571-6 and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior grant 88881.289327/2018-01.Peer reviewedproofPublisher PD

Antimony isotope fractionation through biomethylation

Fermenter cultures with anaerobe bacteria communities (sewage sludge medium) were analysed for volatile and non-volatile methylantimony species.  Gas-samples were analysed by GC-ICP-MS, and fermenter sludge medium and cytosol by HG-GC-ICP-MS.  Trimethylstibine was the sole volatile species, and non-volatile methylantimony species were found in the fermenter sludge medium, but higher levels were found in sludge cytosol. Antimony isotopic fractionation values were determined as high as d 123Sb + 150 in one fermenter experiment.  Additionally, the species-specific isotope ratio ‘fingerprint’ from the methylantimony species confirmed the mechanism proposed by Challenger for the biomethylation process.  It showed the formation of partially methylated antimony species as intermediates.  However, other stimulated bacteria cultures did not show any antimony isotope fractionation through biomethylation. Further investigation into the biomethylation process was studied to determine whether antimonate, Sb(V), is methylated by anaerobe bacteria communities.  For this purpose, isotopically enriched 123Sb(V) was used to monitor the antimony isotope ratio of the methylantimony metabolite species.  The antimonate was stepwise methylated. Environmental gas samples from a landfill site and a digester plant, showed trimethylstibine as the prominent organometal(loid)-species.  Moreover, the biovolatilisation species trimethylstibine was determined to have an antimony isotope fractionation value of d 123Sb + 10. Antimony-glutathione complexes were identified in both in vivo and in vitro studies of antimony interactions with biomolecules.  The molecular structures of these Sb-GS complexes were determined using FI-ESI-MS.  The glutathione influence was then further investigated in a non-enzymatic methylation of antimony with methylcobalamin.  The prominent species produces in vivo was monomethylantimony, with small amount of dimethylantimony.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The Sinorhizobium meliloti LpxXL and AcpXL Proteins Play Important Roles in Bacteroid Development within Alfalfa▿

Free-living Sinorhizobium meliloti lpxXL and acpXL mutants lack lipid A very-long-chain fatty acids (VLCFAs) and have reduced competitiveness in alfalfa. We demonstrate that LpxXL and AcpXL play important but distinct roles in bacteroid development and that LpxXL is essential for the modification of S. meliloti bacteroid lipid A with VLCFAs

Biochemical characterization of Sinorhizobium meliloti mutants reveals gene products involved in the biosynthesis of the unusual lipid a very long-chain fatty acid

Sinorhizobium meliloti forms a symbiosis with the legume alfalfa, whereby it differentiates into a nitrogen-fixing bacteroid. The lipid A species of S. meliloti are modified with very long-chain fatty acids (VLCFAs), which play a central role in bacteroid development. A six-gene cluster was hypothesized to be essential for the biosynthesis of VLCFA-modified lipid A. Previously, two cluster gene products, AcpXL and LpxXL, were found to be essential for S. meliloti lipid A VLCFA biosynthesis. In this paper, we show that the remaining four cluster genes are all involved in lipid A VLCFA biosynthesis. Therefore, we have identified novel gene products involved in the biosynthesis of these unusual lipid modifications. By physiological characterization of the cluster mutant strains, we demonstrate the importance of this gene cluster in the legume symbiosis and for growth in the absence of salt. Bacterial LPS species modified with VLCFAs are substantially less immunogenic than Escherichia coli LPS species, which lack VLCFAs. However, we show that the VLCFA modifications do not suppress the immunogenicity of S. meliloti LPS or affect the ability of S. meliloti to induce fluorescent plant defense molecules within the legume. Because VLCFA-modified lipids are produced by other rhizobia and mammalian pathogens, these findings will also be important in understanding the function and biosynthesis of these unusual fatty acids in diverse bacterial species