Chemical and Structural Insights into the Regioversatility of the Aminoglycoside Acetyltransferase Eis

A recently discovered cause of tuberculosis resistance to a drug of last resort, the aminoglycoside kanamycin, results from modification of this drug by the enhanced intracellular survival (Eis) protein. Eis is a structurally and functionally unique acetyltransferase with an unusual capability of acetylating aminoglycosides at multiple positions. The extent of this regioversatility and its defining protein features are unclear. Herein, we determined the positions and order of acetylation of five aminoglycosides by NMR spectroscopy. This analysis revealed unprecedented acetylation of the 3′′‐amine of kanamycin, amikacin, and tobramycin, and the γ‐amine of the 4‐amino‐2‐hydroxybutyryl group of amikacin. A crystal structure of Eis in complex with coenzyme A and tobramycin revealed how tobramycin can be accommodated in the Eis active site in two binding modes, consistent with its diacetylation. These studies, describing chemical and structural details of acetylation, will guide future efforts towards designing aminoglycosides and Eis inhibitors to overcome resistance in tuberculosis.     

Quantification of polycyclic aromatic hydrocarbons (PAHs) in the smoke from six woods and comparative study of their distribution

Polycyclic aromatic hydrocarbons (PAHs) are considered as undesirable molecules in smoke. It is important to know the smoke composition applied to meat-based products. PAH extracts of the smoke from five tropical woods were fractionated, analyzed then compared to that of beechwood, a European wood commonly used in the smoking industry of meat-based products. The identification and quantification of the aromatic molecules was carried out with gas chromatography coupled to mass spectrometry (GC/MS).     

CD44, γ-H2AX,and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma

Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies. Biopsies were collected prior to treatment from a cohort of 28 patients with non-operable tumours of the oral cavity or oropharynx, and then cultured ex vivo. Short-term biopsy slice culture is a robust method that keeps cells viable for 7 days. Different biomarkers involved in the stemness status (CD44) or the DNA damage response (pATM and γ-H2AX) were investigated for their potential to predict the treatment response. A higher expression of all these markers was predictive of a poor response to treatment. This allowed the stratification of responder or non-responder patients to treatment. Moreover, the ratio for the expression of the three markers 24 h after 4 Gy irradiation versus 0 Gy was higher in responder than in non-responder patients. Finally, combining these biomarkers greatly improved their predictive potential, especially when the γ-H2AX ratio was associated with the CD44 ratio or the pATM ratio. These results encourage further evaluation of these biomarkers in a larger cohort of patients.     

Urban Wastewater Treatment by Catalytic Ozonation

This study focuses on the catalytic ozonation of organic matter recalcitrant to usual water treatment technologies. Experiments aimed to investigate the efficiency of the process TOCCATA®, which uses a granular catalyst coupled with ozonation. Comparison was made between single ozonation, single adsorption onto the catalyst and catalytic ozonation. Adsorption was proven to contribute to decreased dissolved organic carbon. Catalytic ozonation enhanced organic matter removal and ozone transfer compared to single ozonation. Catalytic ozonation was modeled with global apparent first-order kinetics and single adsorption with pseudo–second-order sorption kinetics.