Cytosolic replication in epithelial cells fuels intestinal expansion and chronic fecal shedding of Salmonella Typhimurium

Chong, Audrey; Cooper, Kendal G.; Kari, László; Nilsson, Olof; Hillman, C.; Fleming, Brittany A.; Wang, Qinlu; Nair, Vinod; Steele‐Mortimer, Olivia

doi:10.1016/j.chom.2021.04.017

Cited by 33 publications

(38 citation statements)

References 53 publications

(77 reference statements)

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“…However, the impaired intestinal barrier functions caused by pathogen infection compromises the immune tolerance of the intestines and causes systemic inflammatory responses, which aggravate the systemic immune response and host body damage ( 64 ). As we have known, salmonella invades and destroys the intestinal epithelial cells and then crosses the intestinal epithelial barrier to cause intestinal and even systemic inflammation ( 65 , 66 ). In the current study, significant hemorrhagic spots were observed in the duodenum, jejunum, and ileum on the dpi 42.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Mucosal Immunity-Mediated Modulation of the Gut Microbiome by Oral Delivery of Enterococcus faecium Against Salmonella Enteritidis Pathogenesis in a Laying Hen Model

et al. 2022

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Enterococcus faecium (E. faecium) is a protective role that has crucial beneficial functions on intestinal homeostasis. This study aimed to investigate the effects of E. faecium on the laying performance, egg quality, host metabolism, intestinal mucosal immunity, and gut microbiota of laying hens under the Salmonella Enteritidis (S. Enteritidis) challenge. A total of 400 45-week-old laying hens were randomly divided into four treatments (CON, EF, SCON, and SEF groups) with five replicates for each group and 20 hens per replicate and fed with a basal diet or a basal diet supplemented with E. faecium (2.5 × 108 cfu/g feed). The experiment comprised two phases, consisting of the pre-salmonella challenged phase (from day 14 to day 21) and the post-salmonella challenged phase (from day 21 to day 42). At day 21 and day 22, the hens in SCON and SEF groups were orally challenged with 1.0 ml suspension of 109 cfu/ml S. Enteritidis (CVCC3377) daily, whereas the hens in CON and EF groups received the same volume of sterile PBS. Herein, our results showed that E. faecium administration significantly improved egg production and shell thickness during salmonella infection. Also, E. faecium affected host lipid metabolism parameters via downregulating the concentration of serum triglycerides, inhibited oxidative stress, and enhanced immune functions by downregulating the level of serum malondialdehyde and upregulating the level of serum immunoglobulin G. Of note, E. faecium supplementation dramatically alleviated intestinal villi structure injury and crypt atrophy, and improved intestinal mucosal barrier injuries caused by S. Enteritidis challenge. Moreover, our data revealed that E. faecium supplementation ameliorated S. Enteritidis infection-induced gut microbial dysbiosis by altering the gut microbial composition (reducing Bacteroides, Desulfovibrio, Synergistes, and Sutterella, and increasing Barnesiella, Butyricimonas, Bilophila, and Candidatus_Soleaferrea), and modulating the gut microbial function, such as cysteine and methionine metabolism, pyruvate metabolism, fatty acid metabolism, tryptophan metabolism, salmonella infection, and the PI3K-Akt signaling pathway. Taken together, E. faecium has a strong capacity to inhibit the S. Enteritidis colonization of hens. The results highlight the potential of E. faecium supplementation as a dietary supplement to combat S. Enteritidis infection in animal production and to promote food safety.

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Section: Discussionmentioning

confidence: 99%

Intestinal Mucosal Immunity-Mediated Modulation of the Gut Microbiome by Oral Delivery of Enterococcus faecium Against Salmonella Enteritidis Pathogenesis in a Laying Hen Model

et al. 2022

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“…During intestinal pathogenic bacterial infection, innate immune cells in mice are activated and produce IL-23 and IL-22 to promote antimicrobial peptide production and bacterial clearance. IL-36R signaling promotes IL-23/IL-22/antimicrobial peptide and IL-6/IL-22/antimicrobial peptide-mediated inhibition of intestinal pathogenic bacterial infection by integrating innate and adaptive immune responses (Figure 2) [99].…”

Section: Immune and Inflammatory Signaling Pathwaysmentioning

confidence: 99%

Bacterial and Viral Co-Infection in the Intestine: Competition Scenario and Their Effect on Host Immunity

Lian

Liu

et al. 2022

IJMS

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Bacteria and viruses are both important pathogens causing intestinal infections, and studies on their pathogenic mechanisms tend to focus on one pathogen alone. However, bacterial and viral co-infections occur frequently in clinical settings, and infection by one pathogen can affect the severity of infection by another pathogen, either directly or indirectly. The presence of synergistic or antagonistic effects of two pathogens in co-infection can affect disease progression to varying degrees. The triad of bacterial–viral–gut interactions involves multiple aspects of inflammatory and immune signaling, neuroimmunity, nutritional immunity, and the gut microbiome. In this review, we discussed the different scenarios triggered by different orders of bacterial and viral infections in the gut and summarized the possible mechanisms of synergy or antagonism involved in their co-infection. We also explored the regulatory mechanisms of bacterial–viral co-infection at the host intestinal immune interface from multiple perspectives.

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“…enterica resides within a membrane-bound vacuole within epithelial cells, fibroblasts, macrophages and dendritic cells (reviewed in [11]). However, the intracellular lifestyle of S. enterica differs between cell types, with a proportion of the total bacterial population living freely in the cytosol of epithelial cells, a phenomenon described for Salmonella enterica serovar Typhimurium (S. Typhimurium) and S. Typhi infections in vitro and/or in vivo [12][13][14][15][16][17]. The eventual outcome of epithelial cells harboring cytosolic bacteria is their expulsion from the monolayer into the lumen of the gut and gall bladder [12,[16][17][18][19], serving as a mechanism for bacterial spreading within and between hosts.…”

Section: Introductionmentioning

confidence: 99%

“…However, the intracellular lifestyle of S. enterica differs between cell types, with a proportion of the total bacterial population living freely in the cytosol of epithelial cells, a phenomenon described for Salmonella enterica serovar Typhimurium (S. Typhimurium) and S. Typhi infections in vitro and/or in vivo [12][13][14][15][16][17]. The eventual outcome of epithelial cells harboring cytosolic bacteria is their expulsion from the monolayer into the lumen of the gut and gall bladder [12,[16][17][18][19], serving as a mechanism for bacterial spreading within and between hosts. Notably, the cytosol of macrophages is not permissive for S. Typhimurium replication [20,21], possibly due to nutrient limitation or enhanced host cell innate immune defenses such as autophagy and/or inflammasomes [21].…”

Section: Introductionmentioning

confidence: 99%

Intracellular niche-specific profiling reveals transcriptional adaptations required for the cytosolic lifestyle of Salmonella enterica

et al. 2021

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Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic pathogen that causes diarrheal disease in humans and animals. During salmonellosis, S. Typhimurium colonizes epithelial cells lining the gastrointestinal tract. S. Typhimurium has an unusual lifestyle in epithelial cells that begins within an endocytic-derived Salmonella-containing vacuole (SCV), followed by escape into the cytosol, epithelial cell lysis and bacterial release. The cytosol is a more permissive environment than the SCV and supports rapid bacterial growth. The physicochemical conditions encountered by S. Typhimurium within the epithelial cytosol, and the bacterial genes required for cytosolic colonization, remain largely unknown. Here we have exploited the parallel colonization strategies of S. Typhimurium in epithelial cells to decipher the two niche-specific bacterial virulence programs. By combining a population-based RNA-seq approach with single-cell microscopic analysis, we identified bacterial genes with cytosol-induced or vacuole-induced expression signatures. Using these genes as environmental biosensors, we defined that Salmonella is exposed to oxidative stress and iron and manganese deprivation in the cytosol and zinc and magnesium deprivation in the SCV. Furthermore, iron availability was critical for optimal S. Typhimurium replication in the cytosol, as well as entC, fepB, soxS, mntH and sitA. Virulence genes that are typically associated with extracellular bacteria, namely Salmonella pathogenicity island 1 (SPI1) and SPI4, showed increased expression in the cytosol compared to vacuole. Our study reveals that the cytosolic and vacuolar S. Typhimurium virulence gene programs are unique to, and tailored for, residence within distinct intracellular compartments. This archetypical vacuole-adapted pathogen therefore requires extensive transcriptional reprogramming to successfully colonize the mammalian cytosol.

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Cytosolic replication in epithelial cells fuels intestinal expansion and chronic fecal shedding of Salmonella Typhimurium

Cited by 33 publications

References 53 publications

Intestinal Mucosal Immunity-Mediated Modulation of the Gut Microbiome by Oral Delivery of Enterococcus faecium Against Salmonella Enteritidis Pathogenesis in a Laying Hen Model

Intestinal Mucosal Immunity-Mediated Modulation of the Gut Microbiome by Oral Delivery of Enterococcus faecium Against Salmonella Enteritidis Pathogenesis in a Laying Hen Model

Bacterial and Viral Co-Infection in the Intestine: Competition Scenario and Their Effect on Host Immunity

Intracellular niche-specific profiling reveals transcriptional adaptations required for the cytosolic lifestyle of Salmonella enterica

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