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  1. Article: A

    Gomez, Jasper B / Waters, Christopher M

    bioRxiv : the preprint server for biology

    2024  

    Abstract: A major challenge faced ... ...

    Abstract A major challenge faced by
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.05.588314
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Plasmid-free cheater cells commonly evolve during laboratory growth.

    Bedore, Amber M / Waters, Christopher M

    Applied and environmental microbiology

    2024  Volume 90, Issue 4, Page(s) e0231123

    Abstract: It has been nearly a century since the isolation and use of penicillin, heralding the discovery of a wide range of different antibiotics. In addition to clinical applications, such antibiotics have been essential laboratory tools, allowing for selection ... ...

    Abstract It has been nearly a century since the isolation and use of penicillin, heralding the discovery of a wide range of different antibiotics. In addition to clinical applications, such antibiotics have been essential laboratory tools, allowing for selection and maintenance of laboratory plasmids that encode cognate resistance genes. However, antibiotic resistance mechanisms can additionally function as public goods. For example, extracellular beta-lactamases produced by resistant cells that subsequently degrade penicillin and related antibiotics allow neighboring plasmid-free susceptible bacteria to survive antibiotic treatment. How such cooperative mechanisms impact selection of plasmids during experiments in laboratory conditions is poorly understood. Here, we show in multiple bacterial species that the use of plasmid-encoded beta-lactamases leads to significant curing of plasmids in surface-grown bacteria. Furthermore, such curing was also evident for aminoglycoside phosphotransferase and tetracycline antiporter resistance mechanisms. Alternatively, antibiotic selection in liquid growth led to more robust plasmid maintenance, although plasmid loss was still observed. The net outcome of such plasmid loss is the generation of a heterogenous population of plasmid-containing and plasmid-free cells, leading to experimental confounds that are not widely appreciated.IMPORTANCEPlasmids are routinely used in microbiology as readouts of cell biology or tools to manipulate cell function. Central to these studies is the assumption that all cells in an experiment contain the plasmid. Plasmid maintenance in a host cell typically depends on a plasmid-encoded antibiotic resistance marker, which provides a selective advantage when the plasmid-containing cell is grown in the presence of antibiotic. Here, we find that growth of plasmid-containing bacteria on a surface and to a lesser extent in liquid culture in the presence of three distinct antibiotic families leads to the evolution of a significant number of plasmid-free cells, which rely on the resistance mechanisms of the plasmid-containing cells. This process generates a heterogenous population of plasmid-free and plasmid-containing bacteria, an outcome which could confound further experimentation.
    MeSH term(s) Humans ; Plasmids/genetics ; Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; beta-Lactamases/genetics ; Penicillins/pharmacology
    Chemical Substances Anti-Bacterial Agents ; beta-Lactamases (EC 3.5.2.6) ; Penicillins
    Language English
    Publishing date 2024-03-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 223011-2
    ISSN 1098-5336 ; 0099-2240
    ISSN (online) 1098-5336
    ISSN 0099-2240
    DOI 10.1128/aem.02311-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Switching on cyclic di-GMP heterogeneity in Pseudomonas aeruginosa biofilms.

    Gomez, Jasper B / Waters, Christopher M

    Nature microbiology

    2023  Volume 8, Issue 8, Page(s) 1380–1381

    MeSH term(s) Pseudomonas aeruginosa/genetics ; Biofilms ; Cyclic GMP
    Chemical Substances Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2023-07-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-023-01428-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Vibrio cholerae

    Beckman, Drew A / Waters, Christopher M

    Infection and immunity

    2023  Volume 91, Issue 9, Page(s) e0002623

    Abstract: In its natural aquatic environment, the bacterial ... ...

    Abstract In its natural aquatic environment, the bacterial pathogen
    MeSH term(s) Humans ; Vibrio cholerae/genetics ; Cholera ; Bacteriophages/genetics ; Environment ; Membrane Proteins
    Chemical Substances Membrane Proteins
    Language English
    Publishing date 2023-08-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/iai.00026-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Au naturale: use of biologically derived cyclic di-nucleotides for cancer immunotherapy.

    Waters, Christopher M

    Open biology

    2021  Volume 11, Issue 12, Page(s) 210277

    Abstract: Cyclic di-nucleotides (CDNs) are widespread second messenger signalling molecules that regulate fundamental biological processes across the tree of life. These molecules are also potent modulators of the immune system, inducing a Type I interferon ... ...

    Abstract Cyclic di-nucleotides (CDNs) are widespread second messenger signalling molecules that regulate fundamental biological processes across the tree of life. These molecules are also potent modulators of the immune system, inducing a Type I interferon response upon binding to the eukaryotic receptor STING. Such a response in tumours induces potent immune anti-cancer responses and thus CDNs are being developed as a novel cancer immunotherapy. In this review, I will highlight the use, challenges and advantages of using naturally occurring CDNs to treat cancer.
    MeSH term(s) Biological Factors/chemistry ; Biological Factors/pharmacology ; Biological Factors/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunity, Innate ; Immunotherapy ; Interferon Type I/metabolism ; Membrane Proteins/metabolism ; Molecular Structure ; Neoplasms/drug therapy ; Neoplasms/immunology ; Nucleotides, Cyclic/chemistry ; Nucleotides, Cyclic/pharmacology ; Nucleotides, Cyclic/therapeutic use ; Second Messenger Systems
    Chemical Substances Biological Factors ; Interferon Type I ; Membrane Proteins ; Nucleotides, Cyclic ; STING1 protein, human
    Language English
    Publishing date 2021-12-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2630944-0
    ISSN 2046-2441 ; 2046-2441
    ISSN (online) 2046-2441
    ISSN 2046-2441
    DOI 10.1098/rsob.210277
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Plasmid-free cheater cells commonly evolve during laboratory growth.

    Bedore, Amber M / Waters, Christopher M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: It has been nearly a century since the isolation and use of penicillin, heralding the discovery of a wide range of different antibiotics. In addition to clinical applications, such antibiotics have been essential laboratory tools, allowing for selection ... ...

    Abstract It has been nearly a century since the isolation and use of penicillin, heralding the discovery of a wide range of different antibiotics. In addition to clinical applications, such antibiotics have been essential laboratory tools, allowing for selection and maintenance of laboratory plasmids that encode cognate resistance genes. However, antibiotic resistance mechanisms can additionally function as public goods. For example, secretion of beta-lactamase from resistant cells, and subsequent degradation of nearby penicillin and related antibiotics, allows neighboring plasmid-free susceptible bacteria to survive antibiotic treatment. How such cooperative mechanisms impact selection of plasmids during experiments in laboratory conditions is poorly understood. Here, we show that the use of plasmid-encoded beta-lactamases leads to significant curing of plasmids in surface grown bacteria. Furthermore, such curing was also evident for aminoglycoside phosphotransferase and tetracycline antiporter resistance mechanisms. Alternatively, antibiotic selection in liquid growth led to more robust plasmid maintenance, although plasmid loss still occurred. The net outcome of such plasmid loss is the generation of a heterogenous population of plasmid-containing and plasmid-free cells, leading to experimental confounds that are not widely appreciated.
    Language English
    Publishing date 2023-05-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.19.541508
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Vibrio cholerae phage ICP3 requires O1 antigen for infection.

    Beckman, Drew A / Waters, Christopher M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: In its natural aquatic environment, the bacterial pathogen Vibrio cholerae, the causative agent of the enteric disease cholera, is in constant competition with bacterial viruses known as phages. Following ICP3 infection, V. cholerae cultures that ... ...

    Abstract In its natural aquatic environment, the bacterial pathogen Vibrio cholerae, the causative agent of the enteric disease cholera, is in constant competition with bacterial viruses known as phages. Following ICP3 infection, V. cholerae cultures that exhibited phage killing always recovered overnight, and clones isolated from these regrowth populations exhibited complete resistance to subsequent infections. Whole genome sequencing of these resistant mutants revealed seven distinct mutations in genes encoding for enzymes involved in O1 antigen biosynthesis, demonstrating that the O1 antigen is a previously uncharacterized putative receptor of ICP3. To further elucidate the specificity of the resistance conferred by these mutations, they were challenged with the V. cholerae-specific phages ICP1 and ICP2. All seven O1 antigen mutants demonstrated pan-resistance to ICP1 but not ICP2, which utilizes the OmpU outer membrane protein as a receptor. We show that resistant mutations to ICP1 and ICP3 evolve at a significantly higher frequency than ICP2, but these mutations have a significant fitness tradeoff to V. cholerae and are unable to evolve in the presence of an antimicrobial that mimics host cell defensins.
    Language English
    Publishing date 2023-06-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.31.526503
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: pGpG-signaling regulates virulence and global transcriptomic targets in

    Kharadi, Roshni R / Hsueh, Brian Y / Waters, Christopher M / Sundin, George W

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Cyclic-di-GMP (c-di-GMP) is a critical bacterial second messenger that enables the physiological phase transition ... ...

    Abstract Cyclic-di-GMP (c-di-GMP) is a critical bacterial second messenger that enables the physiological phase transition in
    Language English
    Publishing date 2024-01-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.12.575434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Double take: A dual-functional Hypr GGDEF synthesizes both cyclic di-GMP and cyclic GMP-AMP to control predation in Bdellovibrio bacteriovorus.

    Rangarajan, Aathmaja Anandhi / Waters, Christopher M

    PLoS genetics

    2022  Volume 18, Issue 7, Page(s) e1010263

    MeSH term(s) Antibiosis ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bdellovibrio/metabolism ; Bdellovibrio bacteriovorus/genetics ; Bdellovibrio bacteriovorus/metabolism ; Cyclic GMP ; Gene Expression Regulation, Bacterial ; Nucleotides, Cyclic
    Chemical Substances Bacterial Proteins ; Nucleotides, Cyclic ; cyclic guanosine monophosphate-adenosine monophosphate ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2022-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1010263
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Deployment of a

    Grant, Nkrumah A / Donkor, Gracious Yoofi / Sontz, Jordan T / Soto, William / Waters, Christopher M

    bioRxiv : the preprint server for biology

    2024  

    Abstract: ... Vibrio ... ...

    Abstract Vibrio cholerae
    Language English
    Publishing date 2024-04-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.31.564941
    Database MEDical Literature Analysis and Retrieval System OnLINE

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