A Virulence-Associated Glycolipid with Distinct Conformational Attributes: Impact on Lateral Organization of Host Plasma Membrane, Autophagy, and Signaling.

Mycobacterium tuberculosis (Mtb) serves as the epitome of how lipids-next to proteins-are utilized as central effectors in pathogenesis. It synthesizes an arsenal of structurally atypical lipids (C60-C90) to impact various membrane-dependent steps involved in host interactions. There is a growing precedent to support insertion of these exposed lipids into the host membrane as part of their mode of action. However, the vital role of specific virulence-associated lipids in modulating cellular functions by altering the host membrane organization and associated signaling pathways remain unanswered questions. Here, we combined chemical synthesis, biophysics, cell biology, and molecular dynamics simulations to elucidate host membrane structure modifications and modulation of membrane-associated signaling using synthetic Mycobacterium tuberculosis sulfoglycolipids (Mtb SL). We reveal that Mtb SL reorganizes the host cell plasma membrane domains while showing higher preference for fluid membrane regions. This rearrangement is governed by the distinct conformational states sampled by SL acyl chains. Physicochemical assays with SL analogues reveal insights into their structure-function relationships, highlighting specific roles of lipid acyl chains and headgroup, along with effects on autophagy and cytokine profiles. Our findings uncover a mechanism whereby Mtb uses specific chemical moieties on its lipids to fine-tune host lipid interactions and confer control of the downstream functions by modifying the cell membrane structure and function. These findings will inspire development of chemotherapeutics against Mtb by counteracting their effects on the host-cell membrane.

Biocompatible surface-enhanced Raman scattering nanotags for in vivo cancer detection.

The advancement of surface-enhanced Raman scattering (SERS) is significantly increasing as an ultra-sensitive sensing technology in biomedical research. In this review, we focus on the most recent developments of biocompatible nanoprobes for cancer research. First, we discuss coating approaches to enhance the biocompatibility of SERS substrate and Raman reporters. Furthermore, interesting ligands such as antibodies, aptamers and polypeptides are attached to the surface of nanotags for targeting the cancerous cells in vitro. The unique multiplexing capabilities of the SERS technique have been applied for simultaneous multiple target recognition. Finally, these noninvasive, ultrasensitive tools are mostly highlighted for in vivo tumor detection. Potential application of SERS nanotags in therapeutic study and the possibility of SERS nanotags in biomedical applications are outlined briefly in this review.

Mutagenicity and clastogenicity evaluation of tacrine by Ames and micronucleus assays.

Tacrine was evaluated for its mutagenic and clastogenic activities using the Ames bacterial reverse-mutation assay and the rodent bone marrow micronucleus assay. Tacrine was tested for mutagenic potential at six different concentrations, with 1,250 µg/plate as the highest concentration, followed by five lower concentrations with 2-fold spacing. In clastogenic evaluation, tacrine was administered orally to Wistar rats for 2 days at 5, 10, and 20 mg/kg body weights to assess micronucleus induction in bone marrow erythrocytes. In the Ames assay, tacrine showed nonmutagenicity in four tester strains of Salmonella typhimurium viz. TA98, TA100, TA102, and TA1535, but it was found to be mutagenic in the TA1537 tester strain, both in the presence and absence of a metabolic activation system. Tacrine was found to be nonclastogenic on bone marrow cells of rats at all doses tested and was found to be mutagenic in only the TA1537 strain of Salmonella.