Cheating, trade-offs and the evolution of aggressiveness in a natural pathogen population

The evolutionary dynamics of pathogens are critically important for disease outcomes, prevalence and emergence. In this study we investigate ecological conditions that may promote the long-term maintenance of virulence polymorphisms in pathogen populations. Recent theory predicts that evolution towards increased virulence can be reversed if less-aggressive social 'cheats' exploit more aggressive 'cooperator' pathogens. However, there is no evidence that social exploitation operates within natural pathogen populations. We show that for the bacterium Pseudomonas syringae, major polymorphisms for pathogenicity are maintained at unexpectedly high frequencies in populations infecting the host Arabidopsis thaliana. Experiments reveal that less-aggressive strains substantially increase their growth potential in mixed infections and have a fitness advantage in non-host environments. These results suggest that niche differentiation can contribute to the maintenance of virulence polymorphisms, and that both within-host and between-host growth rates modulate cheating and cooperation in P. syringae populations.     

Docking of the alkaloid geissospermine into acetylcholinesterase: a natural scaffold targeting the treatment of Alzheimer’s disease

Pharmacological studies from our group [Lima et al. Pharmacol Biochem Behav 92:508, (2009)] revealed that geissospermine (GSP), the major alkaloid of the bark extract of Brazilian Geissospermum vellosii, inhibits acetylcholinesterases (AChEs) in the brains of rats and electric eels (Electrophorus electricus). However, the binding mode (i.e., conformation and orientation) of this indole-indoline alkaloid into the AChE active site is unknown. Therefore, in order to propose a plausible binding mode between GSP and AChE, which might explain the observed experimental inhibitory activity, we performed comparative automatic molecular docking simulations using the AutoDock and Molegro Virtual Docker (MVD) programs. A sample of ten crystal structures of the Pacific electric ray (Torpedo californica) TcAChE, in complex with ten diverse active site ligands, was selected as a robust re-docking validation test, and also for GSP docking. The MVD results indicate a preferential binding mode between GSP and AChE, in which GSP functional groups may perform specific interactions with residues in the enzyme active site, according to the ligand–protein contacts detected by the LPC/CSU server. Four hydrogen bonds were detected between GSP and Tyr121, Ser122, Ser200, and His440, in which the last two residues belong to the catalytic triad (Ser200···His440···Glu327). Hydrophobic and π–π stacking interactions were also detected between GSP and Phe330 and Trp84, respectively; these are involved in substrate stabilization at the active site. This study provides the basis to propose structural changes to the GSP structure, such as molecular simplification and isosteric replacement, in order to aid the design of new potential AChE inhibitors that are relevant to the treatment of Alzheimer’s disease.     

Environmental and genetic factors affecting the weaning-estrus interval in sows

We examined the effects of environmental and genetic factors on the weaning-to-estrus interval (WEI) in sows. In order to perform the analyses of the environmental factors, 8104 observations of the 1st to the 6th WEI were carried out, while 6548 observations of the 1st to the 3rd WEI were carried out for the analyses of genetic factors. The environmental model included as fixed effects, herd, genetic line, year and season of birth, as well as the covariates, age of sow at farrowing, litter size at birth and lactation length. Genetic analysis was performed by repeatability and multitrait models. The mean and coefficient of variation for WEI were 7.02 days and 100.6%, respectively. The linear effect of lactation length and the quadratic effect of the age of sow at farrowing affected the WEI. Herd, year and season of farrowing were significant sources of variation for WEI, and there was no influence of genetic line or of litter size at birth. Heritability estimated by the repeatability model was 0.04, while heritabilities obtained by the multitrait model were 0.07, 0.02 and 0.07 for the first three WEI, respectively. Estimates of genetic correlations among the different WEI were of moderate to low magnitude. It was concluded that environmental factors, such as year and season of farrowing, lactation length, age of sow at farrowing and herd, should be considered in the model for best estimation of genetic parameters for this trait. Although with only a small possible genetic gain, selection can be made based on the first WEI.     

How sulphate-reducing microorganisms cope with stress: lessons from systems biology

Sulphate-reducing microorganisms (SRMs) are a phylogenetically diverse group of anaerobes encompassing distinct physiologies with a broad ecological distribution. As SRMs have important roles in the biogeochemical cycling of carbon, nitrogen, sulphur and various metals, an understanding of how these organisms respond to environmental stresses is of fundamental and practical importance. In this Review, we highlight recent applications of systems biology tools in studying the stress responses of SRMs, particularly Desulfovibrio spp., at the cell, population, community and ecosystem levels. The syntrophic lifestyle of SRMs is also discussed, with a focus on system-level analyses of adaptive mechanisms. Such information is important for understanding the microbiology of the global sulphur cycle and for developing biotechnological applications of SRMs for environmental remediation, energy production, biocorrosion control, wastewater treatment and mineral recovery.     

Grazing lucerne as fattening management for young bulls: technical and economic performance and diet authentication

Three fattening systems were evaluated from weaning to slaughter in order to find alternatives to grain feeding in young bulls, and to test the reliability of carcass subcutaneous fat colour to discriminate among them. After weaning (224 kg), one group of animals was fed concentrates and straw until they reached the target slaughter weight (450 kg; Feedlot), another group grazed rotationally on lucerne supplemented with 1.8 kg DM/day barley until slaughter (LUC), and the third group had the same management as LUC animals for 3 months (period 1) and thereafter was finished on concentrates and straw until slaughter (period 2; LUC + Feedlot). Animals were weighed weekly and sampled monthly for serum IGF-I and leptin, and plasma non-esterified fatty acids and carotenoid pigment concentration analyses. Carcass characteristics and subcutaneous fat colour were recorded after slaughter. In period 1, Feedlot animals had slightly greater weight gains than their grazing counterparts (P < 0.10), and at the end of period 1 they had 66% greater IGF-I and 35% greater leptin concentration (P < 0.01). Plasma carotenoid pigments were undetectable in Feedlot animals, but increased during grazing in LUC and LUC + Feedlot treatments. In period 2, weight gains were lowest for LUC, intermediate for Feedlot and greatest for LUC + Feedlot animals (P < 0.001), conditioning the time taken to reach slaughter weight (73, 58 and 47 days, respectively; P < 0.05). Leptin and IGF-I concentrations increased in all management systems during period 2. Plasma carotenoid pigment concentration reached its maximum at the end of period 2 in LUC animals, but it decreased sharply in LUC + Feedlot animals in this period. Management did not affect carcass traits except for subcutaneous fat colour. Yellowness, Chroma (C*) and the value of the integral of the translated reflectance spectrum (SUM), estimator of carotenoid pigment content in fat, were higher in LUC than in LUC + Feedlot and Feedlot animals (P < 0.001). Two logistic regressions were obtained to discriminate carcasses from LUC treatment: P (LUC) = (1 + e(18.8-5.6 × lightness-36.9 × redness + 0.3 × SUM + 29.8 × C*))(-1) and LUC + Feedlot treatment: P (LUC + Feedlot)=(1 + e(833.7-11.8 × lightness + 4.7 × redness + 0.2 × SUM-2.5 × C*))(-1). The economic margin, calculated as income achieved minus costs, was greatest for LUC, intermediate for LUC + Feedlot and lowest for Feedlot treatment. Therefore, grazing lucerne supplemented with barley was an interesting alternative for fattening young bulls in these conditions, producing carcasses of similar quality, which could be accurately traced by measuring subcutaneous fat colour.     

In silico and in vitro investigations of the mutability of disease-causing missense mutation sites in spermine synthase

Background

Spermine synthase (SMS) is a key enzyme controlling the concentration of spermidine and spermine in the cell. The importance of SMS is manifested by the fact that single missense mutations were found to cause Snyder-Robinson Syndrome (SRS). At the same time, currently there are no non-synonymous single nucleoside polymorphisms, nsSNPs (harmless mutations), found in SMS, which may imply that the SMS does not tolerate amino acid substitutions, i.e. is not mutable.

Methodology/Principal Findings

To investigate the mutability of the SMS, we carried out in silico analysis and in vitro experiments of the effects of amino acid substitutions at the missense mutation sites (G56, V132 and I150) that have been shown to cause SRS. Our investigation showed that the mutation sites have different degree of mutability depending on their structural micro-environment and involvement in the function and structural integrity of the SMS. It was found that the I150 site does not tolerate any mutation, while V132, despite its key position at the interface of SMS dimer, is quite mutable. The G56 site is in the middle of the spectra, but still quite sensitive to charge residue replacement.

Conclusions/Significance

The performed analysis showed that mutability depends on the detail of the structural and functional factors and cannot be predicted based on conservation of wild type properties alone. Also, harmless nsSNPs can be expected to occur even at sites at which missense mutations were found to cause diseases.