Publications by authors named "Shaurya Chanana"

9 Publications

  • Page 1 of 1

A marine microbiome antifungal targets urgent-threat drug-resistant fungi.

Science 2020 11;370(6519):974-978

Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.

New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Leveraging the microbiomes of marine animals and cutting-edge metabolomics and genomic tools, we identified encouraging lead antifungal molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent in vitro and mouse-model efficacy toward multiple-drug-resistant fungal pathogens, exhibits a wide safety index, and functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway. The efficacy, safety, and mode of action distinct from other antifungal drugs make turbinmicin a highly promising antifungal drug lead to help address devastating global fungal pathogens such as
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abd6919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756952PMC
November 2020

Draft Genome Sequence of sp. Strain WMMC2535, a Marine Ascidian-Associated Bacterium.

Microbiol Resour Announc 2020 Aug 20;9(34). Epub 2020 Aug 20.

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, USA

WMMC2535, a representative of the myxobacteria (family ), was isolated from a ragged sea hare in the Florida Keys, and its genome was sequenced using PacBio technology. The WMMC2535 genome sequence is the first of this genus and validates the notion that myxobacteria represent outstanding sources of structurally diverse natural products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/MRA.00657-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441232PMC
August 2020

: Automated Hierarchical Clustering and Principal Component Analysis of Large Metabolomic Datasets in R.

Metabolites 2020 Jul 21;10(7). Epub 2020 Jul 21.

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.

Microbial natural product discovery programs face two main challenges today: rapidly prioritizing strains for discovering new molecules and avoiding the rediscovery of already known molecules. Typically, these problems have been tackled using biological assays to identify promising strains and techniques that model variance in a dataset such as PCA to highlight novel chemistry. While these tools have shown successful outcomes in the past, datasets are becoming much larger and require a new approach. Since PCA models are dependent on the members of the group being modeled, large datasets with many members make it difficult to accurately model the variance in the data. Our tool, , first groups strains based on the similarity of their chemical composition, and then applies PCA to the smaller sub-groups yielding more robust PCA models. This allows for scalable chemical comparisons among hundreds of strains with thousands of molecular features. As a proof of concept, we applied our open-source tool to a dataset with 1046 LCMS profiles of marine invertebrate associated bacteria and discovered three new analogs of an established anticancer agent from one promising strain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo10070297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407629PMC
July 2020

MS-Derived Isotopic Fine Structure Reveals Forazoline A as a Thioketone-Containing Marine-Derived Natural Product.

Org Lett 2020 02 4;22(4):1275-1279. Epub 2020 Feb 4.

Pharmaceutical Sciences Division , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States.

Forazoline A is a structurally complex PKS-NRPS hybrid produced by marine-derived sp. During the course of studies highlighting the application of IFS analysis as a powerful tool for natural products analysis, we were alerted to an earlier misinterpretation with respect to forazoline A structure elucidation. In particular, IFS reveals that forazoline A contains a thioketone moiety rarely seen in secondary metabolites and, thus, constitutes an even more intriguing structure than originally thought.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.9b04535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494057PMC
February 2020

Phallusialides A-E, Pyrrole-Derived Alkaloids Discovered from a Marine-Derived sp. Bacterium Using MS-Based Metabolomics Approaches.

J Nat Prod 2019 12 3;82(12):3432-3439. Epub 2019 Dec 3.

Pharmaceutical Sciences Division , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States.

Integrating MS-based metabolomics approaches, LC-MS-PCA and molecular networking enabled the targeted isolation of five new pyrrole-derived alkaloids, phallusialides A-E (-), from a marine-derived sp. bacterium. The structures of - were elucidated by analysis of their HRMS, MS/MS, and NMR spectroscopic data. The absolute configuration of phallusialide A () was determined on the basis of comparisons of experimental and theoretically calculated ECD spectra. Compounds and exhibited antibacterial activity against methicillin resistant (MRSA) and , with MIC values of 32 and 64 μg/mL, respectively, whereas - showed no antibacterial activity even at 256 μg/mL, yielding important SAR insights for this class of compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.9b00808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784719PMC
December 2019

Nanogel-DFO conjugates as a model to investigate pharmacokinetics, biodistribution, and iron chelation in vivo.

Int J Pharm 2018 Mar 16;538(1-2):79-86. Epub 2018 Jan 16.

Department of Pharmaceutical & Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA. Electronic address:

Deferoxamine (DFO) to treat iron overload (IO) has been limited by toxicity issues and short circulation times and it would be desirable to prolong circulation to improve non-transferrin bound iron (NTBI) chelation. In addition, DFO is currently unable to efficiently target the large pool of iron in the liver and spleen. Nanogel-Deferoxamine conjugates (NG-DFO) can prove useful as a model to investigate the pharmacokinetic (PK) properties and biodistribution (BD) behavior of iron-chelating macromolecules and their overall effect on serum ferritin levels. NG-DFO reduced the cytotoxicity of DFO and significantly reduced cellular ferritin levels in IO macrophages in vitro. PK/BD studies in normal rats revealed that NG-DFO displayed prolonged circulation and preferential accumulation into the liver and spleen. IO mice treated with NG1-DFO presented significantly lower levels of serum ferritin compared to DFO. Total renal and fecal elimination data point to the need to balance prolonged circulation with controlled degradation to accelerate clearance of iron-chelating macromolecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2018.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845769PMC
March 2018

Natural Product Discovery Using Planes of Principal Component Analysis in R (PoPCAR).

Metabolites 2017 Jul 13;7(3). Epub 2017 Jul 13.

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.

Rediscovery of known natural products hinders the discovery of new, unique scaffolds. Efforts have mostly focused on streamlining the determination of what compounds are known vs. unknown (dereplication), but an alternative strategy is to focus on what is different. Utilizing statistics and assuming that common actinobacterial metabolites are likely known, focus can be shifted away from dereplication and towards discovery. LC-MS-based principal component analysis (PCA) provides a perfect tool to distinguish unique vs. common metabolites, but the variability inherent within natural products leads to datasets that do not fit ideal standards. To simplify the analysis of PCA models, we developed a script that identifies only those masses or molecules that are unique to each strain within a group, thereby greatly reducing the number of data points to be inspected manually. Since the script is written in R, it facilitates integration with other metabolomics workflows and supports automated mass matching to databases such as Antibase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo7030034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618319PMC
July 2017

Brackish habitat dictates cultivable Actinobacterial diversity from marine sponges.

PLoS One 2017 10;12(7):e0176968. Epub 2017 Jul 10.

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

Bacterial communities associated with marine invertebrates such as sponges and ascidians have demonstrated potential as sources of bio-medically relevant small molecules. Metagenomic analysis has shown that many of these invertebrates harbor populations of Actinobacteria, many of which are cultivable. While some populations within invertebrates are transmitted vertically, others are obtained from the environment. We hypothesized that cultivable diversity from sponges living in brackish mangrove habitats have associations with Actinobacterial populations that differ from those found in clear tropical waters. In this study, we analyzed the cultivable Actinobacterial populations from sponges found in these two distinct habitats with the aim of understanding the secondary metabolite potential. Importantly, we wanted to broadly evaluate the potential differences among these groups to guide future Actinobacterial collection strategies for the purposes of drug discovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176968PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503172PMC
September 2017
-->