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  1. Article ; Online: Reply to: Erroneous predictions of auxotrophies by CarveMe.

    Machado, Daniel / Patil, Kiran R

    Nature ecology & evolution

    2022  Volume 7, Issue 2, Page(s) 196–197

    Language English
    Publishing date 2022-12-05
    Publishing country England
    Document type Letter
    ISSN 2397-334X
    ISSN (online) 2397-334X
    DOI 10.1038/s41559-022-01939-0
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  2. Book ; Thesis: Pathogen mimicry of eurkaryotic linear motifs

    Sámano-Sánchez, Hugo C. / Patil, Kiran Raosaheb / Lanzer, Michael

    2019  

    Institution Universität Heidelberg
    Author's details presented by M.Sc. Hugo Carlos Sámano Sánchez ; referees: Dr. Kiran Patil, Prof. Dr. Michael Lanzer
    Language English
    Size 142 Seiten, Illustrationen, Diagramme, 30 cm
    Publishing place Heidelberg
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Ruperto Carola University Heidelberg, Germany, 2019
    Note Text in Englisch, Zusammenfassung in deutscher und englischer Sprache
    HBZ-ID HT020994186
    Database Catalogue ZB MED Medicine, Health

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    2021 E 830 order for loan Magazin

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  3. Article ; Online: The Pioneer platform: A novel approach for selection of selective anti-cancer cytotoxic activity in bacteria through co-culturing with engineered human cells.

    Garland, Gavin D / Patil, Kiran R / Turner, Suzanne D / Willis, Anne E

    PloS one

    2023  Volume 18, Issue 6, Page(s) e0286741

    Abstract: Most of the small-molecule drugs approved for the treatment of cancer over the past 40 years are based on natural compounds. Bacteria provide an extensive reservoir for the development of further anti-cancer therapeutics to meet the challenges posed by ... ...

    Abstract Most of the small-molecule drugs approved for the treatment of cancer over the past 40 years are based on natural compounds. Bacteria provide an extensive reservoir for the development of further anti-cancer therapeutics to meet the challenges posed by the diversity of these malignant diseases. While identifying cytotoxic compounds is often easy, achieving selective targeting of cancer cells is challenging. Here we describe a novel experimental approach (the Pioneer platform) for the identification and development of 'pioneering' bacterial variants that either show or are conduced to exhibit selective contact-independent anti-cancer cytotoxic activities. We engineered human cancer cells to secrete Colicin M that repress the growth of the bacterium Escherichia coli, while immortalised non-transformed cells were engineered to express Chloramphenicol Acetyltransferase capable of relieving the bacteriostatic effect of Chloramphenicol. Through co-culturing of E. coli with these two engineered human cell lines, we show bacterial outgrowth of DH5α E. coli is constrained by the combination of negative and positive selection pressures. This result supports the potential for this approach to screen or adaptively evolve 'pioneering' bacterial variants that can selectively eliminate the cancer cell population. Overall, the Pioneer platform demonstrates potential utility for drug discovery through multi-partner experimental evolution.
    MeSH term(s) Humans ; Escherichia coli/genetics ; Neoplasms ; Antineoplastic Agents/pharmacology ; Cell Line ; Coculture Techniques
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2023-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0286741
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  4. Article ; Online: Gut reaction: it's not all about enzymes.

    Kamrad, Stephan / Lindell, Anna E / Patil, Kiran R

    Nature metabolism

    2022  Volume 4, Issue 10, Page(s) 1219–1220

    Language English
    Publishing date 2022-10-20
    Publishing country Germany
    Document type Journal Article
    ISSN 2522-5812
    ISSN (online) 2522-5812
    DOI 10.1038/s42255-022-00637-2
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  5. Article ; Online: Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota.

    Lindell, Anna E / Zimmermann-Kogadeeva, Maria / Patil, Kiran R

    Nature reviews. Microbiology

    2022  Volume 20, Issue 7, Page(s) 431–443

    Abstract: The gut microbiota contributes to diverse aspects of host physiology, ranging from immunomodulation to drug metabolism. Changes in the gut microbiota composition are associated with various diseases as well as with the response to medications. It is ... ...

    Abstract The gut microbiota contributes to diverse aspects of host physiology, ranging from immunomodulation to drug metabolism. Changes in the gut microbiota composition are associated with various diseases as well as with the response to medications. It is therefore important to understand how different lifestyle and environmental factors shape gut microbiota composition. Beyond the commonly considered factor of diet, small-molecule drugs have recently been identified as major effectors of the microbiota composition. Other xenobiotics, such as environmental or chemical pollutants, can also impact gut bacterial communities. Here, we review the mechanisms of interactions between gut bacteria and antibiotics, host-targeted drugs, natural food compounds, food additives and environmental pollutants. While xenobiotics can impact bacterial growth and metabolism, bacteria in turn can bioaccumulate or chemically modify these compounds. These reciprocal interactions can manifest in complex xenobiotic-microbiota-host relationships. Our Review highlights the need to study mechanisms underlying interactions with pollutants and food additives towards deciphering the dynamics and evolution of the gut microbiota.
    MeSH term(s) Bacteria/metabolism ; Environmental Pollutants/metabolism ; Food Additives/metabolism ; Gastrointestinal Microbiome/physiology ; Microbiota ; Xenobiotics/metabolism
    Chemical Substances Environmental Pollutants ; Food Additives ; Xenobiotics
    Language English
    Publishing date 2022-01-31
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2139054-X
    ISSN 1740-1534 ; 1740-1526
    ISSN (online) 1740-1534
    ISSN 1740-1526
    DOI 10.1038/s41579-022-00681-5
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  6. Article ; Online: Freeing Yeast from Alcohol Addiction (Just) to Make (It) Fat Instead.

    Patil, Kiran R / Ralser, Markus

    Cell

    2018  Volume 174, Issue 6, Page(s) 1342–1344

    Abstract: Synthetically re-designing eukaryotic metabolism has proven immensely challenging, raising the question of whether evolution has metabolically hardwired eukaryotic cells. Yu et al. now report that, through orchestrating multiple genetic changes and ... ...

    Abstract Synthetically re-designing eukaryotic metabolism has proven immensely challenging, raising the question of whether evolution has metabolically hardwired eukaryotic cells. Yu et al. now report that, through orchestrating multiple genetic changes and laboratory evolution, Saccharomyces metabolism can be reprogrammed from its evolutionary objective of producing ethanol to produce large amounts of free fatty acids.
    MeSH term(s) Alcoholism ; Ethanol ; Fermentation ; Humans ; Lipogenesis ; Saccharomyces cerevisiae
    Chemical Substances Ethanol (3K9958V90M)
    Language English
    Publishing date 2018-09-06
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.08.024
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  7. Article ; Online: Quantification of Duloxetine in the Bacterial Culture and Medium to Study Drug-gut Microbiome Interactions.

    Phapale, Prasad B / Blasche, Sonja / Patil, Kiran R / Alexandrov, Theodore

    Bio-protocol

    2021  Volume 11, Issue 21, Page(s) e4214

    Abstract: Expanding our understanding of drug-gut bacteria interactions requires high-throughput drug measurements in complex bacterial cultures. Quantification of drugs in the cultures, media, and cell pellets is prone to strong matrix effects. We have developed ... ...

    Abstract Expanding our understanding of drug-gut bacteria interactions requires high-throughput drug measurements in complex bacterial cultures. Quantification of drugs in the cultures, media, and cell pellets is prone to strong matrix effects. We have developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method for quantifying duloxetine from high-throughput gut-drug interaction experiments. The method is partially validated for its reproducibility, sensitivity, and accuracy, which makes it suitable for largescale drug screens. We extensively used this method to study biotransformation and bioaccumulation of duloxetine and other drugs in several species of gut bacteria.
    Language English
    Publishing date 2021-11-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325 ; 2331-8325
    ISSN (online) 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.4214
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  8. Article ; Online: metaGEM: reconstruction of genome scale metabolic models directly from metagenomes.

    Zorrilla, Francisco / Buric, Filip / Patil, Kiran R / Zelezniak, Aleksej

    Nucleic acids research

    2021  Volume 49, Issue 21, Page(s) e126

    Abstract: Metagenomic analyses of microbial communities have revealed a large degree of interspecies and intraspecies genetic diversity through the reconstruction of metagenome assembled genomes (MAGs). Yet, metabolic modeling efforts mainly rely on reference ... ...

    Abstract Metagenomic analyses of microbial communities have revealed a large degree of interspecies and intraspecies genetic diversity through the reconstruction of metagenome assembled genomes (MAGs). Yet, metabolic modeling efforts mainly rely on reference genomes as the starting point for reconstruction and simulation of genome scale metabolic models (GEMs), neglecting the immense intra- and inter-species diversity present in microbial communities. Here, we present metaGEM (https://github.com/franciscozorrilla/metaGEM), an end-to-end pipeline enabling metabolic modeling of multi-species communities directly from metagenomes. The pipeline automates all steps from the extraction of context-specific prokaryotic GEMs from MAGs to community level flux balance analysis (FBA) simulations. To demonstrate the capabilities of metaGEM, we analyzed 483 samples spanning lab culture, human gut, plant-associated, soil, and ocean metagenomes, reconstructing over 14,000 GEMs. We show that GEMs reconstructed from metagenomes have fully represented metabolism comparable to isolated genomes. We demonstrate that metagenomic GEMs capture intraspecies metabolic diversity and identify potential differences in the progression of type 2 diabetes at the level of gut bacterial metabolic exchanges. Overall, metaGEM enables FBA-ready metabolic model reconstruction directly from metagenomes, provides a resource of metabolic models, and showcases community-level modeling of microbiomes associated with disease conditions allowing generation of mechanistic hypotheses.
    MeSH term(s) Databases, Genetic ; Gastrointestinal Microbiome/genetics ; Humans ; Metagenome ; Plants/genetics ; Soil Microbiology
    Language English
    Publishing date 2021-10-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkab815
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  9. Article ; Online: Yeast ecology and communities.

    Boynton, Primrose / Patil, Kiran R / Stefanini, Irene / Stelkens, Rike / Cubillos, Francisco A

    Yeast (Chichester, England)

    2022  Volume 39, Issue 1-2, Page(s) 3

    MeSH term(s) Ecology ; Saccharomyces cerevisiae
    Language English
    Publishing date 2022-01-17
    Publishing country England
    Document type Editorial
    ZDB-ID 632636-5
    ISSN 1097-0061 ; 0749-503X
    ISSN (online) 1097-0061
    ISSN 0749-503X
    DOI 10.1002/yea.3691
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  10. Article ; Online: A pathogen-specific isotope tracing approach reveals metabolic activities and fluxes of intracellular Salmonella.

    Mitosch, Karin / Beyß, Martin / Phapale, Prasad / Drotleff, Bernhard / Nöh, Katharina / Alexandrov, Theodore / Patil, Kiran R / Typas, Athanasios

    PLoS biology

    2023  Volume 21, Issue 8, Page(s) e3002198

    Abstract: Pathogenic bacteria proliferating inside mammalian host cells need to rapidly adapt to the intracellular environment. How they achieve this and scavenge essential nutrients from the host has been an open question due to the difficulties in distinguishing ...

    Abstract Pathogenic bacteria proliferating inside mammalian host cells need to rapidly adapt to the intracellular environment. How they achieve this and scavenge essential nutrients from the host has been an open question due to the difficulties in distinguishing between bacterial and host metabolites in situ. Here, we capitalized on the inability of mammalian cells to metabolize mannitol to develop a stable isotopic labeling approach to track Salmonella enterica metabolites during intracellular proliferation in host macrophage and epithelial cells. By measuring label incorporation into Salmonella metabolites with liquid chromatography-mass spectrometry (LC-MS), and combining it with metabolic modeling, we identify relevant carbon sources used by Salmonella, uncover routes of their metabolization, and quantify relative reaction rates in central carbon metabolism. Our results underline the importance of the Entner-Doudoroff pathway (EDP) and the phosphoenolpyruvate carboxylase for intracellularly proliferating Salmonella. More broadly, our metabolic labeling strategy opens novel avenues for understanding the metabolism of pathogens inside host cells.
    MeSH term(s) Animals ; Salmonella ; Salmonella enterica ; Carbon ; Chromatography, Liquid ; Isotopes ; Mammals
    Chemical Substances Carbon (7440-44-0) ; Isotopes
    Language English
    Publishing date 2023-08-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002198
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