Anthranilic Acid Derivatives as Novel Antibiotics against MRSA and other Gram Positive Microorganisms: Combating Antibiotic Resistance

Implementation of antibiotics to treat bacterial infections began during World War II. Since then, a number of antibiotic resistance microorganisms have emerged, one of these being Methicillin Resistant Staphylococcus aureus (MRSA). This resistance can be accredited to multiple factors, but the greatest contributors are the similarity in the chemical composition of the commonly prescribed antibiotics used to treat MRSA and the improper use and disposal of these agents. MRSA is the most frequent health acquired infection in the United States and to combat this growing problem, we have developed a novel class of antibiotics derived from anthranilic acids that show antibacterial activity against MRSA. Our derivatives record a minimum inhibitory concentration (MIC) ranging from 2-64 μg/ml, however when in the presence of human serum protein (HSP) this value increases, decreasing their effectiveness. We have identified a component of HSP, albumin, that causes the increase in MIC, and have determined that intermolecular hydrogen bonding is the cause of this increase. Using this information we are currently synthesizing new derivatives with a low binding affinity for albumin, or when bound do not lose antibacterial activity

Antibacterial Activity of GV-1 Chemical Derivatives in the Presence of Human Serum

Despite advancements in many areas of human medicine, infectious disease continues to be a major cause of mortality worldwide. Improper and excessive use of antibacterial compounds has led to the rise of resistant species of bacteria like Methicillin Resistant Staphylococcus aureus (MRSA). We have discovered a new class of antibiotics that inhibit the growth of Gram-positive bacteria. Upon discovery of inhibition against S. aureus and other Gram-positive bacteria, MRSA, VRE, and other resistant strains were tested. Inhibition by the newly developed compounds on the resistant strains was identical to their inhibition levels against non-resistant strains of these species. We have continued to synthesize and test chemical derivatives of our lead compound in an effort to increase their effectiveness. Overall, these results demonstrate that our carboxylic amide compounds are a novel, non-penicillin based antibiotic that could be used to treat MRSA and other Gram-positive infections

Associations of marker panel scores with feed intake and efficiency traits in beef cattle using preselected single nucleotide polymorphisms

Because of the moderate heritability and the expense associated with collecting feed intake data, effective selection for residual feed intake would be enhanced if marker-assisted evaluation were used for accurate estimation of genetic merit. In this study, a suite of genetic markers predictive of residual feed intake, DMI, and ADG were preselected using singlemarker regression analysis, and the top 100 SNP were analyzed further to provide prediction equations for the traits. The data used consisted of 728 spring-born beef steers, offspring of a cross between a composite dam line and Angus, Charolais, or University of Alberta hybrid bulls. Feed intake data were collected over a 5-yr period, with 2 groups (fall-winter and winter-spring) tested every year. Training and validation data sets were obtained by splitting the data into 2 distinct sets, by randomly splitting the data into training and testing sets based on sire family (split 1) in 5 replicates or by retaining all animals with no known pedigree relationships as the validation set (split 2). A total of 37,959 SNP were analyzed by single-marker regression, of which only the top 100 that corresponded to a Pvalu

Data from: Sustained fitness gains and variability in fitness trajectories in the long-term evolution experiment with Escherichia coli

Many populations live in environments subject to frequent biotic and abiotic changes. Nonetheless, it is interesting to ask whether an evolving population's mean fitness can increase indefinitely, and potentially without any limit, even in a constant environment. A recent study showed that fitness trajectories of Escherichia coli populations over 50 000 generations were better described by a power-law model than by a hyperbolic model. According to the power-law model, the rate of fitness gain declines over time but fitness has no upper limit, whereas the hyperbolic model implies a hard limit. Here, we examine whether the previously estimated power-law model predicts the fitness trajectory for an additional 10 000 generations. To that end, we conducted more than 1100 new competitive fitness assays. Consistent with the previous study, the power-law model fits the new data better than the hyperbolic model. We also analysed the variability in fitness among populations, finding subtle, but significant, heterogeneity in mean fitness. Some, but not all, of this variation reflects differences in mutation rate that evolved over time. Taken together, our results imply that both adaptation and divergence can continue indefinitely—or at least for a long time—even in a constant environment

Candidate genes and single nucleotide polymorphisms associated with variation in residual feed intake in beef cattle

The candidate gene approach was used to identify genes associated with residual feed intake (RFI) in beef steers. The approach uses prior knowledge of gene functions to predict their biological role in the variation observed in a trait. It is suited to identify genes associated with complex traits where each gene has a relatively small effect. First, positional candidate genes were identified within the genomic positions of previously reported QTL associated with component traits related to RFI such as dry matter intake (DMI), growth, feed conversion ratio (FCR), average daily gain (ADG), and energy balance. Secondly, the positional candidate genes were prioritized into functional candidate genes according to their biological functions and their relationship with the biological processes associated with RFI including carbohydrate, fat and protein metabolism, thermoregulation, immunity and muscle activity. Single nucleotide polymorphisms (SNPs) located within the functional candidate genes were identified using mRNA sequences and prioritized into functional classes such as non-synonymous (nsSNP), synonymous (sSNP) or intronic SNP. A total of 117 nsSNP were considered as functional SNP and genotyped in steers at the University of Alberta ranch in Kinsella. Multiple marker association analysis in ASReml was performed using RFI data obtained from 531 beef steers. Twenty-five SNP were significantly associated with RFI (P < 0.05) accounting for 19.7% of the phenotypic variation. Using SIFT program to predict the effect of the SNP on the function of the corresponding protein, 3 of the 25 SNP were predicted to cause a significant effect on protein function (P < 0.05). One of the 3 SNP was located in the GHR gene and was also associated with a significant effect on the tertiary structure of the GHR protein (P < 0.05) as modeled using SWISSModel software. Least square means for each genotype were estimated and an over-dominance effect was observed for the SNP located in the GHR, CAST, ACAD11 and UGT3A1 genes. In addition, 2 other SNP showed a dominance effect and 3 genes had an additive effect. Gene network analysis performed in Ingenuity pathway analysis (IPA) software (Ingenuity Systems, www.ingenuity.com) indicated that the significant genes were involved in biological pathways such as lipid, protein and energy metabolism, electron transport and membrane signaling. The genes in this study, if validated in other beef cattle populations, may be useful for marker assisted selection for feed efficiency