Biology subjects

Poliseno, L.

Publications and source records attributed to Poliseno, L..

2 recordsLinked to original sources

bioRxiv2025

The mycomembrane differentially and heterogeneously restricts antibiotic permeation

The recalcitrance of Mycobacterium tuberculosis to antibiotic treatment has been broadly attributed to the impermeability of the organisms outer mycomembrane. However, the studies that support this inference have been indirect and/or reliant on bulk population measurements. We previously developed the Peptidoglycan Accessibility Click-Mediated AssessmeNt (PAC-MAN) method to covalently trap azide-modified small molecules in the peptidoglycan cell wall of live mycobacteria, after they have traversed the mycomembrane. Using PAC-MAN we now show that the mycomembrane differentially restricts access of fluorophores and antibiotic derivatives. Mycomembranes of both M. tuberculosis and the model organism M. smegmatis discriminate between divergent classes of antibiotics as well as between antibiotics within a single family, the fluoroquinolones. By analyzing sub-populations of M. tuberculosis and M. smegmatis, we also found that some fluorophores and vancomycin are heterogeneously restricted by the mycomembrane. Our data indicate that the mycomembrane is a molecule- and cell-specific barrier to antibiotic permeation. Abstract Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/630956v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@4bdeb7org.highwire.dtl.DTLVardef@10ade47org.highwire.dtl.DTLVardef@872dceorg.highwire.dtl.DTLVardef@d04b59_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2020

An Eutherian-Specific microRNA Controls the Translation of Satb2 in a Model of Cortical Differentiation

Cerebral cortical development is controlled by key transcription factors that specify the neuronal identities in the different cortical layers. These transcription factors are crucial for the identity of the different neurons, but the mechanisms controlling their expression in distinct cells are only partially known. Here we investigate the expression and stability of the mRNAs of Tbr1, Bcl11b, Fezf2, Satb2 and Cux1 in single developing mouse cortical cells. We focus on Satb2 and find that its mRNA expression occurs much earlier than its protein synthesis and in a set of cells broader than expected, suggesting an initially tight control of its translation, which is subsequently de-repressed at late developmental stages. Mechanistically, Satb2 3UTR modulates protein translation of GFP reporters during mouse corticogenesis. By in vitro pull-down of Satb2 3UTR-associated miRNAs, we select putative miRNAs responsible for SATB2 inhibition, focusing on those strongly expressed in early progenitor cells and reduced in late cells. miR-541, an Eutherian-specific miRNA, and miR-92a/b are the best candidates and their inactivation triggers robust and premature SATB2 translation in both mouse and human cortical cells. Our findings indicate that RNA interference plays a major role in the timing of cortical cell identity and may be part of the toolkit involved in specifying supra-granular projection neurons.

developmental biology↗