Anti-SAT1 monoclonal antibody Made to order

Background Airway epithelial injury is a crucial component of acute and severe asthma pathogenesis and a promising target for treatment of refractory asthma. However, the underlying mechanism of epithelial injury remains poorly explored. Although high levels of polyamines, mainly spermine, have been found in asthma and comorbidity, their role in airway epithelial injury and the cause of their altered levels in asthma have not been explored. Methods Results We measured key polyamine metabolic enzymes in lung samples from normal and asthmatic subjects and in mice with OVA-induced allergic airway inflammation (AAI). Polyamine metabolism was modulated using pharmacologic/genetic modulators. Epithelial stress and apoptosis were measured by TSLP levels and TUNEL assay, respectively. We found loss of the polyamine catabolic enzymes spermidine/spermine-N (1)-acetyltransferase-1 (SAT1) and spermine oxidase (SMOX) predominantly in bronchial epithelial cells (BECs) of human asthmatic lung samples and mice with AAI. In naive mice, SAT1 or SMOX knockdown led to airway hyper-responsiveness, remodeling, and BEC apoptosis. Conversely, in mice with AAI, overexpression of either SAT1 or SMOX alleviated asthmatic features and reduced TSLP levels and BEC apoptosis. Similarly, while pharmacological induction of SAT1 and SMOX using the polyamine analogue bis(ethyl)norspermine (BENSPM) alleviated asthmatic features with reduced TSLP levels and BEC apoptosis, pharmacological inhibition of these enzymes using BERENIL or MDL72527, respectively, worsened them. Spermine accumulation in lungs correlated with BEC apoptosis, and spermine treatment caused apoptosis of human BEAS-2B cells in vitro. Conclusions Spermine induces BEC injury. Induction of polyamine catabolism may represent a novel therapeutic approach for asthma via reversing BEC stress.

Objectives: A carbapenem-resistant Morganella morganii clinical isolate that was phenotypically metallo-beta-lactamase (MBL)-positive was recovered from a Greek patient. The aim of the study was to analyse the structure of the integron containing the MBL gene. Methods: MICs were determined by the broth microdilution method. PCR assays and nucleotide sequencing were used for identification of bla, gene types and mapping of the integron carrying the MBL gene. The location of the MBL allele was investigated by mating experiments and plasmid analysis as well as by Southern blotting of the plasmid extract and gene-specific hybridization with a bla(VIM-1) probe. Results: The strain contained In3Mor, a novel class 1 integron carrying a carbapenemase gene (bla(VIM-1)) associated with a trimethoprim (dfrA1), a streptothricin (sat1) and two aminoglycoside resistance genes (aacA7 and aadAl). Conjugation experiments failed to detect a transferable MBL determinant and plasmid DNA was not visualized. The chromosomal location of bla(VIM-1) was confirmed after hybridization of the chromosomal band with the bla(VIM-1) probe. Conclusions: Production of a VIM-type MBL in a M. morganii clinical isolate is documented in this study for the first time. Also, the dfrA1-sat1-aadA1 array which is typically described in the variable region of class 2 integrons consistent with that on Tn 7 transposons, is originally detected herein in a class 1 integron.