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  1. Article ; Online: Emergent antibiotic persistence in a spatially structured synthetic microbial mutualism.

    Xiong, Xianyi / Othmer, Hans G / Harcombe, William R

    The ISME journal

    2024  

    Abstract: Antibiotic persistence (heterotolerance) allows a sub-population of bacteria to survive antibiotic-induced killing and contributes to the evolution of antibiotic resistance. Although bacteria typically live in microbial communities with complex ... ...

    Abstract Antibiotic persistence (heterotolerance) allows a sub-population of bacteria to survive antibiotic-induced killing and contributes to the evolution of antibiotic resistance. Although bacteria typically live in microbial communities with complex ecological interactions, little is known about how microbial ecology affects antibiotic persistence. Here, we demonstrated within a synthetic two-species microbial mutualism of Escherichia coli and Salmonella enterica that the combination of cross-feeding and community spatial structure can emergently cause high antibiotic persistence in bacteria by increasing the cell-to-cell heterogeneity. Tracking ampicillin-induced death for bacteria on agar surfaces, we found that E. coli forms up to 55 times more antibiotic persisters in the cross-feeding coculture than in monoculture. This high persistence could not be explained solely by the presence of S. enterica, the presence of cross-feeding, average nutrient starvation, or spontaneous resistant mutations. Time-series fluorescent microscopy revealed increased cell-to-cell variation in E. coli lag time in the mutualistic co-culture. Furthermore, we discovered that an E. coli cell can survive antibiotic killing if the nearby S. enterica cells on which it relies die first. In conclusion, we showed that the high antibiotic persistence phenotype can be an emergent phenomenon caused by a combination of cross-feeding and spatial structure. Our work highlights the importance of considering spatially structured interactions during antibiotic treatment and understanding microbial community resilience more broadly.
    Language English
    Publishing date 2024-05-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2406536-5
    ISSN 1751-7370 ; 1751-7362
    ISSN (online) 1751-7370
    ISSN 1751-7362
    DOI 10.1093/ismejo/wrae075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Bonn / Germany

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  2. Article ; Online: Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community.

    Adamowicz, Elizabeth M / Harcombe, William R

    Antimicrobial agents and chemotherapy

    2020  Volume 64, Issue 11

    Abstract: With the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, in which multiple drugs are used to treat an infection, has proven highly successful in the treatment of ... ...

    Abstract With the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, in which multiple drugs are used to treat an infection, has proven highly successful in the treatment of cancer and HIV. However, this practice has proven challenging for the treatment of bacterial infections due to difficulties in selecting the correct combinations and dosages. An additional challenge in infection treatment is the polymicrobial nature of many infections, which may respond to antibiotics differently than a monoculture pathogen. This study tests whether patterns of antibiotic interactions (synergy, antagonism, or independence/additivity) in monoculture can be used to predict antibiotic interactions in an obligate cross-feeding coculture. Using our previously described weakest-link hypothesis, we hypothesized antibiotic interactions in coculture based on the interactions we observed in monoculture. We then compared our predictions to observed antibiotic interactions in coculture. We tested the interactions between 10 previously identified antibiotic combinations using checkerboard assays. Although our antibiotic combinations interacted differently than predicted in our monocultures, our monoculture results were generally sufficient to predict coculture patterns based solely on the weakest-link hypothesis. These results suggest that combination therapy for cross-feeding multispecies infections may be successfully designed based on antibiotic interaction patterns for their component species.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Bacterial Infections ; Drug Synergism ; Humans ; Microbial Sensitivity Tests
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2020-10-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.00465-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 809: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Einzelsignatur: Show issues

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  3. Article ; Online: Refining the stress gradient hypothesis in a microbial community.

    Hammarlund, Sarah P / Harcombe, William R

    Proceedings of the National Academy of Sciences of the United States of America

    2019  Volume 116, Issue 32, Page(s) 15760–15762

    MeSH term(s) Bacteria ; Microbiota
    Language English
    Publishing date 2019-07-18
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1910420116
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: The Power of Metabolism for Predicting Microbial Community Dynamics.

    Chacón, Jeremy M / Harcombe, William R

    mSystems

    2019  Volume 4, Issue 3

    Abstract: Quantitative understanding and prediction of microbial community dynamics are an outstanding challenge. We test the hypothesis that metabolic mechanisms provide a foundation for accurate prediction of dynamics in microbial systems. In our research, ... ...

    Abstract Quantitative understanding and prediction of microbial community dynamics are an outstanding challenge. We test the hypothesis that metabolic mechanisms provide a foundation for accurate prediction of dynamics in microbial systems. In our research, metabolic models have been able to accurately predict species interactions, evolutionary trajectories, and response to perturbation in simple synthetic consortia. However, metabolic models have many constraints and often serve best as null models to identify additional processes at play. We anticipate that major advances in metabolic systems biology will involve scaling bottom-up approaches to complex communities and expanding the processes that are incorporated in a metabolic perspective. Ultimately, cellular metabolism will inform predictive ecology that enables precision management of microbial systems.
    Language English
    Publishing date 2019-06-11
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5077
    ISSN 2379-5077
    DOI 10.1128/mSystems.00146-19
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  5. Article ; Online: Bacteriophage specificity is impacted by interactions between bacteria.

    Bisesi, Ave T / Möbius, Wolfram / Nadell, Carey D / Hansen, Eleanore G / Bowden, Steven D / Harcombe, William R

    mSystems

    2024  Volume 9, Issue 3, Page(s) e0117723

    Abstract: Predators play a central role in shaping community structure, function, and stability. The degree to which bacteriophage predators (viruses that infect bacteria) evolve to be specialists with a single bacterial prey species versus generalists able to ... ...

    Abstract Predators play a central role in shaping community structure, function, and stability. The degree to which bacteriophage predators (viruses that infect bacteria) evolve to be specialists with a single bacterial prey species versus generalists able to consume multiple types of prey has implications for their effect on microbial communities. The presence and abundance of multiple bacterial prey types can alter selection for phage generalists, but less is known about how interactions between prey shape predator specificity in microbial systems. Using a phenomenological mathematical model of phage and bacterial populations, we find that the dominant phage strategy depends on prey ecology. Given a fitness cost for generalism, generalist predators maintain an advantage when prey species compete, while specialists dominate when prey are obligately engaged in cross-feeding interactions. We test these predictions in a synthetic microbial community with interacting strains of
    Importance: There is significant natural diversity in how many different types of bacteria a bacteriophage can infect, but the mechanisms driving this diversity are unclear. This study uses a combination of mathematical modeling and an
    MeSH term(s) Bacteriophages/physiology ; Bacteria ; Escherichia coli/physiology ; Bacterial Physiological Phenomena ; Symbiosis
    Language English
    Publishing date 2024-02-20
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5077
    ISSN (online) 2379-5077
    DOI 10.1128/msystems.01177-23
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  6. Article ; Online: Increasing growth rate slows adaptation when genotypes compete for diffusing resources.

    Chacón, Jeremy M / Shaw, Allison K / Harcombe, William R

    PLoS computational biology

    2020  Volume 16, Issue 1, Page(s) e1007585

    Abstract: The rate at which a species responds to natural selection is a central predictor of the species' ability to adapt to environmental change. It is well-known that spatially-structured environments slow the rate of adaptation due to increased intra-genotype ...

    Abstract The rate at which a species responds to natural selection is a central predictor of the species' ability to adapt to environmental change. It is well-known that spatially-structured environments slow the rate of adaptation due to increased intra-genotype competition. Here, we show that this effect magnifies over time as a species becomes better adapted and grows faster. Using a reaction-diffusion model, we demonstrate that growth rates are inextricably coupled with effective spatial scales, such that higher growth rates cause more localized competition. This has two effects: selection requires more generations for beneficial mutations to fix, and spatially-caused genetic drift increases. Together, these effects diminish the value of additional growth rate mutations in structured environments.
    MeSH term(s) Adaptation, Biological/genetics ; Genetic Drift ; Genotype ; Models, Genetic ; Mutation/genetics ; Population Growth ; Selection, Genetic/genetics
    Language English
    Publishing date 2020-01-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1007585
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  7. Article ; Online: Limitation by a shared mutualist promotes coexistence of multiple competing partners.

    Hammarlund, Sarah P / Gedeon, Tomáš / Carlson, Ross P / Harcombe, William R

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 619

    Abstract: Although mutualisms are often studied as simple pairwise interactions, they typically involve complex networks of interacting species. How multiple mutualistic partners that provide the same service and compete for resources are maintained in mutualistic ...

    Abstract Although mutualisms are often studied as simple pairwise interactions, they typically involve complex networks of interacting species. How multiple mutualistic partners that provide the same service and compete for resources are maintained in mutualistic networks is an open question. We use a model bacterial community in which multiple 'partner strains' of Escherichia coli compete for a carbon source and exchange resources with a 'shared mutualist' strain of Salmonella enterica. In laboratory experiments, competing E. coli strains readily coexist in the presence of S. enterica, despite differences in their competitive abilities. We use ecological modeling to demonstrate that a shared mutualist can create temporary resource niche partitioning by limiting growth rates, even if yield is set by a resource external to a mutualism. This mechanism can extend to maintain multiple competing partner species. Our results improve our understanding of complex mutualistic communities and aid efforts to design stable microbial communities.
    MeSH term(s) Amino Acids/biosynthesis ; Escherichia coli/physiology ; Microbiota ; Models, Biological ; Salmonella enterica/growth & development ; Salmonella enterica/physiology
    Chemical Substances Amino Acids
    Language English
    Publishing date 2021-01-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-20922-0
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  8. Article ; Online: Harnessing intercellular signals to engineer the soil microbiome.

    Connolly, Jack A / Harcombe, William R / Smanski, Michael J / Kinkel, Linda L / Takano, Eriko / Breitling, Rainer

    Natural product reports

    2022  Volume 39, Issue 2, Page(s) 311–324

    Abstract: Covering: Focus on 2015 to 2020Plant and soil microbiomes consist of diverse communities of organisms from across kingdoms and can profoundly affect plant growth and health. Natural product-based intercellular signals govern important interactions ... ...

    Abstract Covering: Focus on 2015 to 2020Plant and soil microbiomes consist of diverse communities of organisms from across kingdoms and can profoundly affect plant growth and health. Natural product-based intercellular signals govern important interactions between microbiome members that ultimately regulate their beneficial or harmful impacts on the plant. Exploiting these evolved signalling circuits to engineer microbiomes towards beneficial interactions with crops is an attractive goal. There are few reports thus far of engineering the intercellular signalling of microbiomes, but this article argues that it represents a tremendous opportunity for advancing the field of microbiome engineering. This could be achieved through the selection of synergistic consortia in combination with genetic engineering of signal pathways to realise an optimised microbiome.
    MeSH term(s) Bacteria/genetics ; Crops, Agricultural ; Microbiota ; Plant Roots ; Soil ; Soil Microbiology
    Chemical Substances Soil
    Language English
    Publishing date 2022-02-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2002546-4
    ISSN 1460-4752 ; 0265-0568
    ISSN (online) 1460-4752
    ISSN 0265-0568
    DOI 10.1039/d1np00034a
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  9. Article: Mutualism reduces the severity of gene disruptions in predictable ways across microbial communities.

    Martinson, Jonathan N V / Chacón, Jeremy M / Smith, Brian A / Villarreal, Alex R / Hunter, Ryan C / Harcombe, William R

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Predicting evolution in microbial communities is critical for problems from human health to global nutrient cycling. Understanding how species interactions impact the distribution of fitness effects for a focal population would enhance our ability to ... ...

    Abstract Predicting evolution in microbial communities is critical for problems from human health to global nutrient cycling. Understanding how species interactions impact the distribution of fitness effects for a focal population would enhance our ability to predict evolution. Specifically, it would be useful to know if the type of ecological interaction, such as mutualism or competition, changes the average effect of a mutation (i.e., the mean of the distribution of fitness effects). Furthermore, how often does increasing community complexity alter the impact of species interactions on mutant fitness? To address these questions, we created a transposon mutant library in
    Language English
    Publishing date 2023-05-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.08.539835
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Disentangling a metabolic cross-feeding in a halophilic archaea-bacteria consortium.

    Medina-Chávez, Nahui Olin / Torres-Cerda, Abigail / Chacón, Jeremy M / Harcombe, William R / De la Torre-Zavala, Susana / Travisano, Michael

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1276438

    Abstract: Microbial syntrophy, a cooperative metabolic interaction among prokaryotes, serves a critical role in shaping communities, due to the auxotrophic nature of many microorganisms. Syntrophy played a key role in the evolution of life, including the ... ...

    Abstract Microbial syntrophy, a cooperative metabolic interaction among prokaryotes, serves a critical role in shaping communities, due to the auxotrophic nature of many microorganisms. Syntrophy played a key role in the evolution of life, including the hypothesized origin of eukaryotes. In a recent exploration of the microbial mats within the exceptional and uniquely extreme Cuatro Cienegas Basin (CCB), a halophilic isolate, designated as AD140, emerged as a standout due to its distinct growth pattern. Subsequent genome sequencing revealed AD140 to be a co-culture of a halophilic archaeon from the
    Language English
    Publishing date 2023-12-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1276438
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