How to cope with the quest for new antibiotics

Since their introduction in therapy, antibiotics have played an essential role in human society, saving millions of lives, allowing safe surgery, organ transplants, cancer therapy. Antibiotics have also helped to elucidate several biological mechanisms and boosted the birth and growth of pharmaceutical companies, generating profits and royalties. The golden era of antibiotics and the scientific and economical drive of big pharma towards these molecules is long gone, but the need for effective antibiotics is increased as their pipelines dwindle and multi-resistant pathogenic strains spread. Here we outline some strategies that could help meet this emergency and list promising new targets.     

Cadmium retention in rice roots is influenced by cadmium availability, chelation and translocation

Analysis of rice plants exposed to a broad range of relatively low and environmentally realistic Cd concentrations showed that the root capacity to retain Cd ions rose from 49 to 79%, corresponding to increases in the external Cd2+ concentration in the 0.01-1 μM range. Fractioning of Cd ions retained by roots revealed that different events along the metal sequestration pathway (i.e. chelation by thiols, vacuolar compartmentalization, adsorption) contributed to Cd immobilization in the roots. However, large amounts of Cd ions (around 24% of the total amount) predictable as potentially mobile were still found in all conditions, while the amount of Cd ions loaded in the xylem seemed to have already reached saturation at 0.1 μM Cd2+, suggesting that Cd translocation may also play an indirect role in determining Cd root retention, especially at the highest external concentrations. In silico search and preliminary analyses in yeast suggest OsHMA2 as a good candidate for the control of Cd xylem loading in rice. Taken as a whole, data indicate Cd chelation, compartmentalization, adsorption and translocation processes as components of a complex 'firewall system' which acts in limiting Cd translocation from the root to the shoot and which reaches different equilibrium positions depending on Cd external concentration.     

A New Critical Conformational Determinant of Multidrug Efflux by an MFS Transporter

Secondary multidrug (Mdr) transporters utilize ion concentration gradients to actively remove antibiotics and other toxic compounds from cells. The model Mdr transporter MdfA from Escherichia coli exchanges dissimilar drugs for protons. The transporter should open at the cytoplasmic side to enable access of drugs into the Mdr recognition pocket. Here we show that the cytoplasmic rim around the Mdr recognition pocket represents a previously overlooked important regulatory determinant in MdfA. We demonstrate that increasing the positive charge of the electrically asymmetric rim dramatically inhibits MdfA activity and sometimes even leads to influx of planar, positively charged compounds, resulting in drug sensitivity. Our results suggest that unlike the mutants with the electrically modified rim, the membrane-embedded wild-type MdfA exhibits a significant probability of an inward-closed conformation, which is further increased by drug binding. Since MdfA binds drugs from its inward-facing environment, these results are intriguing and raise the possibility that the transporter has a sensitive, drug-induced conformational switch, which favors an inward-closed state.     

Triterpenoids of Terminalia sericea

The structures of sericic acid and sericoside, the major constituents of the roots of Terminalia sericea, have been determined. Sericic acid is 2α,3β,19α,24-tetrahydroxy-olean-12-en-28-oic acid and sericoside the corresponding C-28 D-glucosyl ester.     

Structure and absolute stereochemistry of vanillosmin,a guaianolide from Vanillosmopsis erythropappa

The structure and absolute stereochemistry of vanillosmin were established by chemical and spectral evidence and by comparison with O-acetyl-isophoto-α-santonic lactone and tetrahydroartabsin “C”.     

Plant metabolomics in biotic and abiotic stress: a critical overview

Abiotic and biotic stresses affect plant physiology and growth. The development of metabolomics, along with other -omics technologies, allowed in depth analysis of the reactive processes characterizing plant stress as the result of the alteration of metabolites and gene expressions. Here, we organize and interpret data from 151 studies to provide an overview about metabolomic shift after exposure to either abiotic or biotic stresses including drought, salinity, heat, heavy metal, cold, pathogens and insects. Data showed that amino acids, organic acids, sugars, and sugar alcohols quantities are influenced by stresses. Proline for example, increased in almost every stress condition, while other molecules increased or decreased depending specifically on plant tissue, plant species and type of applied stress. We concluded that although it is difficult to predict precisely what a stress will cause, some general metabolic trends can be described and improve our understanding of plant response to biotic and abiotic stresses.