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

Faber, Franziska; Thiennimitr, Parameth; Spiga, Luisella; Byndloss, Mariana X.; Litvak, Yael; Lawhon, Sara D.; Andrews‐Polymenis, Helene; Winter, Sebastian; Bäumler, Andreas J.

doi:10.1371/journal.ppat.1006129

Cited by 144 publications

(134 citation statements)

References 46 publications

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“…To address the contribution of the FnrS‐ and ArcZ‐mediated regulation to virulence in the host, we used oral mouse competition assays (dependent on the SPI1 T3SS), and intraperitoneal (IP) infection (bypassing the need for SPI1). Streptomycin treatment of mice leads to availability of anaerobic terminal electron acceptors as well as oxygen (Clark and Barrett, ; Stecher and Hardt, ; Winter et al , ; ; Thiennimitr et al , ; Lopez et al , ; Faber et al , ). Given the role of these sRNAs in regulating aspects of respiration (Papenfort et al , ; Durand and Storz, ; Mandin and Gottesman, ), we tested the effects of removing FnrS and ArcZ in normal (Strep‐) or streptomycin‐treated (Strep+) mice.…”

Section: Resultsmentioning

confidence: 99%

Oxygen‐dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium

Kim

Golubeva

Vanderpool

et al. 2018

Molecular Microbiology

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Summary Salmonella Typhimurium induces inflammatory diarrhea and uptake into intestinal epithelial cells using the Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS). Three AraC‐like regulators, HilD, HilC and RtsA, form a feed‐forward regulatory loop that activates transcription of hilA, encoding the activator of the T3SS structural genes. Many environmental signals and regulatory systems are integrated into this circuit to precisely regulate SPI1 expression. A subset of these regulatory factors affects translation of hilD, but the mechanisms are poorly understood. Here, we identified two sRNAs, FnrS and ArcZ, which repress hilD translation, leading to decreased production of HilA. FnrS and ArcZ are oppositely regulated in response to oxygen, one of the key environmental signals affecting expression of SPI1. Mutational analysis demonstrates that FnrS and ArcZ bind to the hilD mRNA 5′ UTR, resulting in translational repression. Deletion of fnrS led to increased HilD production under low‐aeration conditions, whereas deletion of arcZ abolished the regulatory effect on hilD translation aerobically. The fnrS arcZ double mutant has phenotypes in a mouse oral infection model consistent with increased expression of SPI1. Together, these results suggest that coordinated regulation by these two sRNAs maximizes HilD production at an intermediate level of oxygen.

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Section: Resultsmentioning

confidence: 99%

Oxygen‐dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium

Kim

Golubeva

Vanderpool

et al. 2018

Molecular Microbiology

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“…In vitro , Salmonella is known to utilize a great variety of compounds as the sole carbon source during aerobic conditions (Gutnick et al, 1969). In the murine gut, only few carbon sources have been identified, such as ethanolamine, 1,2 propanediol, and fructose-asparagine (Ali et al, 2014; Faber et al, 2017; Thiennimitr et al, 2011). An oxidative TCA cycle may explain why utilization of these compounds in vivo strictly requires respiration.…”

Section: Discussionmentioning

confidence: 99%

An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate

Spiga

Winter

Carvalho

et al. 2017

Cell Host & Microbe

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128

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SUMMARY The mucosal inflammatory response induced by Salmonella Typhimurium creates a favorable niche for this gut pathogen. Conventional wisdom holds that S. Typhimurium undergoes an incomplete TCA cycle in the anaerobic mammalian gut. One change during S. Typhimurium-induced inflammation is the production of oxidized compounds by infiltrating neutrophils. We show that inflammation-derived electron acceptors induce a complete, oxidative TCA cycle in S. Typhimurium, allowing the bacteria to compete with the microbiota for colonization. A complete TCA cycle facilitates utilization of the microbiota-derived fermentation end product succinate as a carbon source. S. Typhimurium succinate utilization genes contribute to efficient colonization in conventionally raised mice, but provide no growth advantage in germ-free mice. Mono-association of gnotobiotic mice with Bacteroides, a major succinate producer, restores succinate utilization in S. Typhimurium. Thus, oxidative central metabolism enables S. Typhimurium to utilize a variety of carbon sources, including microbiota-derived succinate.

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“…In the intestine, both mucosa‐associated and luminal neutrophils engulf Salmonella . However, infiltrating PMNs also promote intestinal inflammation, thereby increasing the risk of bacterial invasion, and produce ROS, which can transform carbon sources such as thiosulfate in the intestinal lumen into tetrathionate and the microbial fermentation product 1,2‐propanediol, allowing NTS to outgrow the competing microbiota . PMNs also release calprotectin into the intestinal milieu where it sequesters zinc, further restricting the growth of the intestinal microbiota .…”

Section: Intestinal and Invasive Nts Infectionsmentioning

confidence: 99%

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Mooney

Galloway

Riley

2018

Journal of Leukocyte Biology

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Invasive bacterial disease is well described in immunocompromised hosts, including those with malaria infection. One bacterial infection frequently observed in children with Plasmodium falciparum infection is nontyphoidal salmonella (NTS) infection, in which a typically intestinal infection becomes systemic with serious, often fatal, consequences. In this review, we consider the role of malaria‐induced immunoregulatory responses in tipping the balance from tissue homeostasis during malaria infection to risk of invasive NTS. Also, neutrophils are crucial in the clearance of NTS but their ability to mount an oxidative burst and kill intracellular Salmonella is severely compromised during, and for some time after, an acute malaria infection. Here, we summarize the evidence linking malaria and invasive NTS infections; describe the role of neutrophils in clearing NTS infections; review evidence for neutrophil dysfunction in malaria infections; and explore roles of heme oxygenase‐1, IL‐10, and complement in mediating this dysfunction. Finally, given the epidemiological evidence that low density, subclinical malaria infections pose a risk for invasive NTS infections, we consider whether the high prevalence of such infections might underlie the very high incidence of invasive bacterial disease across much of sub‐Saharan Africa.

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

Cited by 144 publications

References 46 publications

Oxygen‐dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium

Oxygen‐dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium

An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

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