Giving structure to the biofilm matrix: an overview of individual strategies and emerging common themes

Biofilms are communities of microbial cells that underpin diverse processes including sewage bioremediation, plant growth promotion, chronic infections and industrial biofouling. The cells resident in the biofilm are encased within a self-produced exopolymeric matrix that commonly comprises lipids, proteins that frequently exhibit amyloid-like properties, eDNA and exopolysaccharides. This matrix fulfils a variety of functions for the community, from providing structural rigidity and protection from the external environment to controlling gene regulation and nutrient adsorption. Critical to the development of novel strategies to control biofilm infections, or the capability to capitalize on the power of biofilm formation for industrial and biotechnological uses, is an in-depth knowledge of the biofilm matrix. This is with respect to the structure of the individual components, the nature of the interactions between the molecules and the three-dimensional spatial organization. We highlight recent advances in the understanding of the structural and functional role that carbohydrates and proteins play within the biofilm matrix to provide three-dimensional architectural integrity and functionality to the biofilm community. We highlight, where relevant, experimental techniques that are allowing the boundaries of our understanding of the biofilm matrix to be extended using Escherichia coli, Staphylococcus aureus, Vibrio cholerae, and Bacillus subtilis as exemplars.

The signature of fine scale local adaptation in Atlantic salmon revealed from common garden experiments in nature

Understanding the extent, scale and genetic basis of local adaptation is important for conservation and management. Its relevance in salmonids at microgeographic scales, where dispersal (and hence potential gene flow) can be substantial, has however been questioned. Here we compare the fitness of communally-reared offspring of local and foreign Atlantic salmon Salmo salar from adjacent Irish rivers and reciprocal F1 hybrid crosses between them, in the wild ‘home’ environment of the local population. Experimental groups did not differ in wild smolt output but a catastrophic flood event may have limited our ability to detect freshwater performance differences, which were evident in a previous study. Foreign parr exhibited higher, and hybrids intermediate, emigration rates from the natal stream relative to local parr, consistent with genetically-based behavioural differences. Adult return rates were lower for the foreign compared to the local group. Overall lifetime success of foreigners and hybrids relative to locals was estimated at 31% and 40% (mean of both hybrid groups), respectively. The results imply a genetic basis to fitness differences among populations separated by only 50km, driven largely by variation in smolt to adult return rates. Hence even if supplementary stocking programs obtain broodstock from neighbouring rivers, the risk of extrinsic outbreeding depression may be high.

Contribution of sewage organic matter to the diet of the common limpet near the former outflow at Blackhead, Northern Ireland

Stable isotopes (δ13C, δ15N) have been used to document the utilisation of sewage effluent in coastal marine foodwebs in a number of studies (e.g. Rau et al. 1981; Risk et al. 2009; Rogers 1999; 2003). δ13C and, especially, δ15N showed clear differences in the diet of common limpets (Patella vulgata) collected in June 2010 near the untreated sewage outfall at Blackhead, Northern Ireland and a ‘clean’ site nearby. Because sewage contains a significant portion of fossil-fuel derived compounds (Law et al. 2013), 14C measurements enabled us to estimate the contribution of fossil carbon to the effluent and to the foodweb and hence of the level of sewage contamination. The effluent was found to contain 12.2 ± x % fossil carbon on the day sampled. The modern marine carbon endmember is enriched by the discharge from the Sellafield nuclear fuel reprocessing plant across the Irish Sea (c.f. Cook et al. 2004) so 14C analyses of samples from the ‘clean’ site were needed. We found that 38.5 ±x % of the diet of common limpets collected near the sewage was derived from fossil fuel. We plan to collect samples from the same two sites in June 2014 to establish whether the 2012 relocation of the outfall, with preliminary treated discharge farther out to sea has eliminated the contamination at Blackhead

Shared common variants in prostate cancer and blood lipids

BACKGROUND: Epidemiological and clinical studies suggest comorbidity between prostate cancer (PCA) and cardiovascular disease (CVD) risk factors. However, the relationship between these two phenotypes is still not well understood. Here we sought to identify shared genetic loci between PCA and CVD risk factors.

METHODS: We applied a genetic epidemiology method based on conjunction false discovery rate (FDR) that combines summary statistics from different genome-wide association studies (GWAS), and allows identification of genetic overlap between two phenotypes. We evaluated summary statistics from large, multi-centre GWA studies of PCA (n=50 000) and CVD risk factors (n=200 000) [triglycerides (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, body mass index, waist-hip ratio and type 2 diabetes (T2D)]. Enrichment of single nucleotide polymorphisms (SNPs) associated with PCA and CVD risk factors was assessed with conditional quantile-quantile plots and the Anderson-Darling test. Moreover, we pinpointed shared loci using conjunction FDR.

RESULTS: We found the strongest enrichment of P-values in PCA was conditional on LDL and conditional on TG. In contrast, we found only weak enrichment conditional on HDL or conditional on the other traits investigated. Conjunction FDR identified altogether 17 loci; 10 loci were associated with PCA and LDL, 3 loci were associated with PCA and TG and additionally 4 loci were associated with PCA, LDL and TG jointly (conjunction FDR <0.01). For T2D, we detected one locus adjacent to HNF1B.

CONCLUSIONS: We found polygenic overlap between PCA predisposition and blood lipids, in particular LDL and TG, and identified 17 pleiotropic gene loci between PCA and LDL, and PCA and TG, respectively. These findings provide novel pathobiological insights and may have implications for trials using targeting lipid-lowering agents in a prevention or cancer setting.

COP and clathrin-coated vesicle budding:different pathways, common approaches

Vesicle and tubule transport containers move proteins and lipids from one membrane system to another. Newly forming transport containers frequently have electron-dense coats. Coats coordinate the accumulation of cargo and sculpt the membrane. Recent advances have shown that components of both COP1 and clathrin-adaptor coats share the same structure and the same motif-based cargo recognition and accessory factor recruitment mechanisms, which leads to insights on conserved aspects of coat recruitment, polymerisation and membrane deformation. These themes point to the way in which evolutionarily conserved features underpin these diverse pathways.

Association of common gene variants in the WNT/β-catenin pathway with colon cancer recurrence

Wnt/β-catenin signaling has a central role in the development and progression of most colon cancers (CCs). Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II CC. A total of 234 patients treated with 5-fluorouracil-based chemotherapy were included in this study. Whole-blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4, NOTCH2 and GLI1 genes by PCR-based restriction fragment-length polymorphism or direct DNA sequencing. Polymorphisms with statistical significance were validated in an independent study cohort. The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (10.7 vs 4.9 years; hazard ratio: 2.48; 95% CI, 0.96-6.38; P=0.04) in high-risk stage II CC patients. This result remained significant in multivariate Cox's regression analysis. This study shows that the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for CC patients after 5-fluorouracil-based adjuvant therapy.