Dumpster Diving in the Gut: Bacterial Microcompartments as Part of a Host-Associated Lifestyle

Jakobson, Christopher M.; Tullman‐Ercek, Danielle

doi:10.1371/journal.ppat.1005558

Cited by 40 publications

(49 citation statements)

References 32 publications

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“…Typhimurium-induced colitis [6, 21, 32, 33], which enables the pathogen to consume 1,2-propanediol, a process that could be viewed as “dumpster diving” for a fermentation product produced by the gut microbiota [34] (Fig 5). Respiration of 1,2-propanediol allows S .…”

Section: Discussionmentioning

confidence: 99%

Respiration of Microbiota-Derived 1,2-propanediol Drives Salmonella Expansion during Colitis

et al. 2017

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Intestinal inflammation caused by Salmonella enterica serovar Typhimurium increases the availability of electron acceptors that fuel a respiratory growth of the pathogen in the intestinal lumen. Here we show that one of the carbon sources driving this respiratory expansion in the mouse model is 1,2-propanediol, a microbial fermentation product. 1,2-propanediol utilization required intestinal inflammation induced by virulence factors of the pathogen. S. Typhimurium used both aerobic and anaerobic respiration to consume 1,2-propanediol and expand in the murine large intestine. 1,2-propanediol-utilization did not confer a benefit in germ-free mice, but the pdu genes conferred a fitness advantage upon S. Typhimurium in mice mono-associated with Bacteroides fragilis or Bacteroides thetaiotaomicron. Collectively, our data suggest that intestinal inflammation enables S. Typhimurium to sidestep nutritional competition by respiring a microbiota-derived fermentation product.

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Section: Discussionmentioning

confidence: 99%

Respiration of Microbiota-Derived 1,2-propanediol Drives Salmonella Expansion during Colitis

et al. 2017

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“…It is now well established that a subset of BMCs contributes to the fitness and virulence of some pathogenic bacteria 17 . The human gut 12,96 and processed food 97,98 are enriched in propanediol and ethanolamine that can be catabolized by the EUT, PDU and some GRM BMCs as a source of energy, carbon and nitrogen.…”

Section: The Functional Diversity Of Bmcsmentioning

confidence: 99%

“…The human gut 12,96 and processed food 97,98 are enriched in propanediol and ethanolamine that can be catabolized by the EUT, PDU and some GRM BMCs as a source of energy, carbon and nitrogen. For example, the PDU BMC of Salmonella typhimurium was found to contribute to colonization and expansion during infection, possibly by making use of nutrients that are unavailable to the normal flora 17,99,100 . Similarly, the EUT BMCs of Listeria monocytogenes , enterohemorrhagic Escherichia coli O157:H7, Enterococcus faecalis , and S. typhimurium have been shown to be important for virulence in the host intestine in both in vivo and in vitro infection models 101–106 .…”

Section: The Functional Diversity Of Bmcsmentioning

confidence: 99%

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Bacterial microcompartments

et al. 2018

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Bacterial microcompartments (BMCs) are self-assembling organelles that consist of an enzymatic core that is encapsulated by a selectively permeable protein shell. The potential to form BMCs is widespread, found across the Kingdom Bacteria. BMCs have crucial roles in carbon dioxide fixation in autotrophs and the catabolism of organic substrates in heterotrophs. They contribute to the metabolic versatility of bacteria, providing a competitive advantage in specific environmental niches. Although BMCs were first visualized more than sixty years ago, it is mainly in the last decade that progress has been made in understanding their metabolic diversity and the structural basis of their assembly and function. This progress has not only heightened our understanding of their role in microbial metabolism but it is also beginning to enable their use in a variety of applications in synthetic biology. In this Review, we focus on recent insights into the structure, assembly, diversity and function of BMCs.

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“…MCP metabolons allow the growth of these pathogens on carbon and energy sources, such as 1,2-propanediol [4] and ethanolamine [5], that confer a competitive advantage upon invasion of the host gut [6][7][8][9][10]. MCPs are typically approximately 150 nm in diameter, with multiple enzymes localized inside a porous, monolayer shell composed of several distinct proteins [4,11,12]; a typical bacterial cell contains several MCP structures when in the presence of the appropriate substrate.…”

Section: Introductionmentioning

confidence: 99%

A Systems-Level Model Reveals That 1,2-Propanediol Utilization Microcompartments Enhance Pathway Flux Through Intermediate Sequestration

Jakobson¹,

Slininger

Tullman‐Ercek³

et al. 2016

Preprint

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The spatial organization of metabolism is common to all domains of life. Enteric and other bacteria use subcellular organelles known as bacterial microcompartments to spatially organize the metabolism of pathogenicity-relevant carbon sources, such as 1,2-propanediol. The organelles are thought to sequester a private cofactor pool, minimize the effects of toxic intermediates, and enhance flux through the encapsulated metabolic pathways. We develop a mathematical model of the function of the 1,2-propanediol utilization microcompartment of Salmonella enterica and use it to analyze the function of the microcompartment organelles in detail. Our model makes accurate estimates of doubling times based on an optimized compartment shell permeability determined by maximizing metabolic flux in the model. The compartments function primarily to decouple cytosolic intermediate concentrations from the concentrations in the microcompartment, allowing significant enhancement in pathway flux by the generation of large concentration gradients across the microcompartment shell. We find that selective permeability of the microcompartment shell is not absolutely necessary, but is often beneficial in establishing this intermediate-trapping function. Our findings also implicate active transport of the 1,2-propanediol substrate under conditions of low external substrate concentration, and we present a mathematical bound, in terms of external 1,2-propanediol substrate concentration and diffusive rates, on when active transport of the substrate is advantageous. By allowing us to predict experimentally inaccessible aspects of microcompartment function, such as intra-microcompartment metabolite concentrations, our model presents avenues for future research and underscores the importance of carefully considering changes in external metabolite concentrations and other conditions during batch cultures. Our results also suggest that the encapsulation of heterologous pathways in bacterial microcompartments might yield significant benefits for pathway flux, as well as for toxicity mitigation. Funding: This work was supported by the National Science Foundation (award MCB1150567 to DTE) https://www.nsf.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author SummaryMany bacterial species, such as Salmonella enterica (responsible for over 1 million illnesses per year in the United States) and Yersinia pestis (the causative agent of bubonic plague), have a suite of unique metabolic capabilities allowing them to proliferate in the hostile environment of the host gut. Bacterial microcompartments are the subcellular organelles that contain the enzymes responsible for these special metabolic pathways. In this study, we use a mathematical model to explore the possible reasons why Salmonella enclose the 1,2-propanediol utilization metabolic pathway within these sophisticated organelle structures. Using our model, we can examine experimentally inaccessible aspects of the...

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Dumpster Diving in the Gut: Bacterial Microcompartments as Part of a Host-Associated Lifestyle

Cited by 40 publications

References 32 publications

Respiration of Microbiota-Derived 1,2-propanediol Drives Salmonella Expansion during Colitis

Respiration of Microbiota-Derived 1,2-propanediol Drives Salmonella Expansion during Colitis

Bacterial microcompartments

A Systems-Level Model Reveals That 1,2-Propanediol Utilization Microcompartments Enhance Pathway Flux Through Intermediate Sequestration

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