Experimental approaches to phenotypic diversity in infection

Kreibich, Saskia; Hardt, Wolf‐Dietrich

doi:10.1016/j.mib.2015.06.007

Cited by 37 publications

(28 citation statements)

References 137 publications

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“…The substantial progress in understanding intracellular Salmonella metabolism is encouraging, but one crucial, previously neglected aspect is just emerging. All experimental and in silico methods are based on population averages, but recent work has shown extensive heterogeneity between infected host cells and individual Salmonella cells in terms of microenvironments, stress, gene expression, overall metabolic activities, growth rates, and cell fates (Bumann, ; Helaine & Kugelberg, ; Knodler, ; Kreibich & Hardt, ; Mills & Avraham, ; Saliba & Vogel, ). Differential nutrient access seems to cause heterogeneous Salmonella growth rates during systemic infection in vivo, with important consequences for disease progression and tolerance against antimicrobial chemotherapy (Claudi et al, ).…”

Section: Methods For Investigating Intracellular Salmonella Metabolismmentioning

confidence: 99%

“…This includes nitric oxide, which can block respiration (Husain et al, ); itaconic acid, which inhibits the glyoxylate shunt (Michelucci et al, ); and superoxide/peroxide that damages several bacterial components whose repair requires supportive metabolism (Burton et al, ; Slauch, ). Importantly, many of these host/ Salmonella interactions are highly heterogeneous with strong cell‐to‐cell variation on both the host cell and the Salmonella side (Bumann, ; Helaine & Kugelberg, ; Knodler, ; Kreibich & Hardt, ; Mills & Avraham, ; Saliba & Vogel, ).…”

Section: Goals For Studying Intracellular Salmonella Metabolismmentioning

confidence: 99%

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IntracellularSalmonellametabolism

Bumann

Schothorst

2017

Cellular Microbiology

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Growth of Salmonella inside infected host cells is a key aspect of their ability to cause local enteritis or systemic disease. This growth depends on exploitation of host nutrients through a large Salmonella metabolism network with hundreds of metabolites and enzymes. Studies in cell culture infection models are unravelling more and more of the underlying molecular and cellular mechanisms but also show striking Salmonella metabolic plasticity depending on host cell line and experimental conditions. In vivo studies have revealed a qualitatively diverse, but quantitatively poor, host-Salmonella nutritional interface, which on one side makes Salmonella fitness largely resilient against metabolic perturbations, but on the other side severely limits Salmonella biomass generation and growth rates. This review discusses goals and techniques for studying Salmonella intracellular metabolism, summarises main results and implications, and proposes key issues that could be addressed in future studies.

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Section: Methods For Investigating Intracellular Salmonella Metabolismmentioning

confidence: 99%

Section: Goals For Studying Intracellular Salmonella Metabolismmentioning

confidence: 99%

IntracellularSalmonellametabolism

Bumann

Schothorst

2017

Cellular Microbiology

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“…Alternative probes smaller than antibodies are being developed such as nanobodies, aptamers and other non-protein biomolecules (Ngo et al, 2016;Sahl et al, 2017). Current imaging techniques also reveals phenotypic heterogeneity of microbial and cellular populations that can be further studied by systems biology approaches (Bumann, 2015;Kreibich & Hardt, 2015). Many microbial pathogens interact in complex microenvironments with diverse host microbiota, dynamic polymicrobial communities that start to be successfully imaged by specific techniques such as passive clarity technique (Fung et al, 2019;Yang et al, 2014) and light sheet fluorescence microscopy (Parthasarathy, 2018).…”

Section: Perspectivesmentioning

confidence: 99%

Three decades of listeriology through the prism of technological advances

Impens

Dussurget

2020

Cellular Microbiology

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Decades of breakthroughs resulting from cross feeding of microbiological research and technological innovation have promoted Listeria monocytogenes to the rank of model microorganism to study host–pathogen interactions. The extraordinary capacity of this bacterium to interfere with a vast array of host cellular processes uncovered new concepts in microbiology, cell biology and infection biology. Here, we review technological advances that revealed how bacteria and host interact in space and time at the molecular, cellular, tissue and whole body scales, ultimately revolutionising our understanding of Listeria pathogenesis. With the current bloom of multidisciplinary integrative approaches, Listeria entered a new microbiology era.

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“…The resulting rich diversity of pathogen behavior has been largely ignored until recently, in part because available methodology provided only bulk average readouts that could not resolve variation between pathogen subpopulations. However, in the past few years, single-cell approaches have been starting to reveal fascinating diversity of host-pathogen interactions in infected tissues [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of Salmonella-host interactions in infected host tissues

Bumann

Cunrath

2017

Current Opinion in Microbiology

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Infected host tissues have complex anatomy, diverse cell types, and dynamic inflammation. Traditional infection biology approaches largely ignore this complex host environment and its impact on pathogens, but recent single-cell technologies unravel extensively heterogeneous host-pathogen interactions in vivo. Salmonella are major model pathogens in this field due to the availability of excellent mouse disease models and facile molecular biology. The results show how Salmonella stochastically vary their virulence, exploit differential nutrient availability, experience and respond to widely varying stresses, and have disparate fates ranging from vigorous proliferation to eradication within the same host tissue. Specific Salmonella subsets drive disease progression, while others persist during antimicrobial chemotherapy. Further elucidation of the underlying mechanisms could provide a basis for improved infection control.

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Experimental approaches to phenotypic diversity in infection

Cited by 37 publications

References 137 publications

IntracellularSalmonellametabolism

IntracellularSalmonellametabolism

Three decades of listeriology through the prism of technological advances

Heterogeneity of Salmonella-host interactions in infected host tissues

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