Salmonella enterica serovar Typhimurium uses anaerobic respiration to overcome propionate-mediated colonization resistance

Shelton, Catherine; Yoo, Woongjae; Shealy, Nicolas G.; Torres, Teresa P.; Zieba, Jacob K.; Calcutt, M. Wade; Foegeding, Nora J.; Kim, Dajeong; Kim, Jinshil; Ryu, Sangryeol; Byndloss, Mariana X.

doi:10.1016/j.celrep.2021.110180

Cited by 49 publications

(44 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, it has recently been shown that propionate metabolism is linked to intestinal expansion by S . Typhimurium in the inflamed gut (Shelton et al, 2022). Taken together, these findings suggest that independent mutations in barA and sirA acquired by late isolates in independent patients lead to largely (though not completely) overlapping transcriptomic changes, which include the downregulation of numerous SPI-1- and SPI-4-encoded factors and associated effectors.…”

Section: Resultsmentioning

confidence: 99%

Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway

Grote

Piscon

McGuire

et al. 2022

Preprint

View full text Add to dashboard Cite

The bacterial pathogen Salmonella enterica is able to establish persistent infections, evading antibiotics and the host immune system and providing a reservoir for recrudescence and transmission to new hosts. Non-typhoidal serovars (NTS) of S. enterica can establish and maintain symptomatic and asymptomatic long term human infections that may predispose carriers to inflammatory bowel diseases and cancer. Defining the adaptations and host-pathogen interactions enabling these persistent infections is key to devising more effective strategies to combat and prevent persistent bacterial infections. Using comparative genomics of 639 Salmonella NTS isolates belonging to 49 serovars that were longitudinally obtained from 256 salmonelosis patients during different stages of infection, we identified numerous genetic variations accruing over time in strains isolated from the same patient. Many of these changes were found in the same gene across multiple patients and serovars. Among these variant loci, genes encoding global transcriptional regulators were found to be the most commonly mutated between early and late same-patient isolates. Genetic changes in the SirA/BarA two-component regulatory system were particularly frequent, with mutations identified in 24 independent patients. Comparative RNA-Seq analysis revealed that distinct mutations in sirA/barA that arose independently in late isolates of multiple patients lead to significantly diminished expression of virulence-associated genes encoded in the Salmonella Pathogenicity Islands (SPIs) 1 and 4, many of which are known to be critical for host cell invasion and the production of enteritis. Using the salmonellosis mouse model we showed that these mutations in sirA/barA genes confer attenuated virulence in-vivo. Taken together, these data suggest that selection of mutations in the SirA/BarA pathway facilitates persistent Salmonella infection in humans, possibly by attenuating Salmonella virulence and its ability to cause inflammation.

show abstract

Section: Resultsmentioning

confidence: 99%

Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway

Grote

Piscon

McGuire

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The use of tetrathionate and nitrate as terminal electron acceptors allows Salmonella to use poorly fermentable carbon sources such as ethanolamine derived from enterocytes membrane; fructose-asparagine derived from host diet; and 1,2-propanediol, succinate, and propionate that are by-products of microbial fermentation [17,19,[93][94][95]. The exploitation of these carbon sources ensures a growth advantage over commensal bacteria, which solely rely on fermentation for growth [17,19,[93][94][95].…”

Section: Inflammation and The Newly Created Nichementioning

confidence: 99%

Revisiting the steps of Salmonella gut infection with a focus on antagonistic interbacterial interactions

et al. 2021

View full text Add to dashboard Cite

A commensal microbial community is established in the mammalian gut during its development, and these organisms protect the host against pathogenic invaders. The hallmark of noninvasive Salmonella gut infection is the induction of inflammation via effector proteins secreted by the type III secretion system, which modulate host responses to create a new niche in which the pathogen can overcome the colonization resistance imposed by the microbiota. Several studies have shown that endogenous microbes are important to control Salmonella infection by competing for resources. However, there is limited information about antimicrobial mechanisms used by commensals and pathogens during these in vivo disputes for niche control. This review aims to revisit the steps that Salmonella needs to overcome during gut colonization—before and after the induction of inflammation—to achieve an effective infection. We focus on a series of reported and hypothetical antagonistic interbacterial interactions in which both contact‐independent and contact‐dependent mechanisms might define the outcome of the infection.

show abstract

“…In addition, the gut microbiota protects the host by limiting enteric pathogen expansion (colonization resistance) partially via nutrient sequestration (Caballero-Flores et al, 2020; Krautkramer et al, 2021; Oliphant and Allen-Vercoe, 2019). Enteric pathogens, such as Salmonella enterica serovar Typhimurium ( S. Tm) and carcinogenic pks + Escherichia coli ( E. coli ) have evolved to overcome colonization resistance by inducing and/or thriving during intestinal inflammation (colitis) (Arthur and Jobin, 2013; Arthur et al, 2014; Bronner et al, 2018; Faber et al, 2017; Shelton et al, 2022; Thiennimitr et al, 2011; Zhu et al, 2019). One of the critical mechanisms driving a luminal expansion of pathogenic Enterobacteriaceae during colitis is the generation of respiratory electron acceptors as a byproduct of the inflammatory host response.…”

Section: Introductionmentioning

confidence: 99%

Microbiota-derived aspartate drives pathogenic Enterobacteriaceae expansion in the inflamed gut

Yoo

Zieba

Shealy

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

SUMMARYInflammation boosts the availability of electron acceptors in the intestinal lumen creating a favorable niche for pathogenic Enterobacteriaceae. However, the mechanisms linking intestinal inflammation-mediated changes in luminal metabolites and pathogen expansion remain unclear. Here, we show that mucosal inflammation induced by Salmonella enterica serovar Typhimurium (S. Tm) infection and chemical colitis results in increased intestinal levels of the amino acid aspartate. The S. Tm and E. coli genomes encode an aspartate ammonia-lyase (aspA) which converts aspartate into fumarate, an alternative electron acceptor. S. Tm and pathogenic E. coli used aspA-dependent fumarate respiration for growth in the murine gut only during inflammation. Such growth advantage was abolished in the gut of germ-free mice. However, mono-association of gnotobiotic mice with members of the classes Bacteroidia and Clostridia restored the benefit of aspartate utilization to the pathogens. Our findings demonstrate the role of microbiota-derived amino acids in driving respiration-dependent Enterobacteriaceae expansion during colitis.

show abstract

Salmonella enterica serovar Typhimurium uses anaerobic respiration to overcome propionate-mediated colonization resistance

Abstract: Highlights d Nitrate-dependent anaerobic respiration enables propionate metabolism by S. Tm d Propionate metabolism supports S. Tm intestinal expansion in the inflamed gut d Propionate utilization by S. Tm is dependent on the SPI-1 effector SopE d Bacteroides-derived propionate fuels S.

Cited by 49 publications

References 53 publications

Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway

Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway

Revisiting the steps of Salmonella gut infection with a focus on antagonistic interbacterial interactions

Microbiota-derived aspartate drives pathogenic Enterobacteriaceae expansion in the inflamed gut

Contact Info

Product

Resources

About