scholarly journals Salmonella -Mediated Inflammation Eliminates Competitors for Fructose-Asparagine in the Gut

2018 ◽  
Vol 86 (5) ◽  
Author(s):  
Jikang Wu ◽  
Anice Sabag-Daigle ◽  
Mikayla A. Borton ◽  
Linnea F. M. Kop ◽  
Blake E. Szkoda ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Salmonella Enterica ◽  
Intestinal Tract ◽  
Intestinal Inflammation ◽  
Dry Weight ◽  
Pathogenicity Islands ◽  
Content Type ◽  
Gain Access

ABSTRACT Salmonella enterica elicits intestinal inflammation to gain access to nutrients. One of these nutrients is fructose-asparagine (F-Asn). The availability of F-Asn to Salmonella during infection is dependent upon Salmonella pathogenicity islands 1 and 2, which in turn are required to provoke inflammation. Here, we determined that F-Asn is present in mouse chow at approximately 400 pmol/mg (dry weight). F-Asn is also present in the intestinal tract of germfree mice at 2,700 pmol/mg (dry weight) and in the intestinal tract of conventional mice at 9 to 28 pmol/mg. These findings suggest that the mouse intestinal microbiota consumes F-Asn. We utilized heavy-labeled precursors of F-Asn to monitor its formation in the intestine, in the presence or absence of inflammation, and none was observed. Finally, we determined that some members of the class Clostridia encode F-Asn utilization pathways and that they are eliminated from highly inflamed Salmonella -infected mice. Collectively, our studies identify the source of F-Asn as the diet and that Salmonella -mediated inflammation is required to eliminate competitors and allow the pathogen nearly exclusive access to this nutrient.

scholarly journals A Salmonella Virulence Factor Activates the NOD1/NOD2 Signaling Pathway

mBio ◽  
2011 ◽  
Vol 2 (6) ◽  
Author(s):  
A. Marijke Keestra ◽  
Maria G. Winter ◽  
Daisy Klein-Douwel ◽  
Mariana N. Xavier ◽  
Sebastian E. Winter ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Content Type ◽  
Type Iii

ABSTRACTThe invasion-associated type III secretion system (T3SS-1) ofSalmonella entericaserotype Typhimurium (S. Typhimurium) activates the transcription factor NF-κB in tissue culture cells and induces inflammatory responses in animal models through unknown mechanisms. Here we show that bacterial delivery or ectopic expression of SipA, a T3SS-1-translocated protein, led to the activation of the NOD1/NOD2 signaling pathway and consequent RIP2-mediated induction of NF-κB-dependent inflammatory responses. SipA-mediated activation of NOD1/NOD2 signaling was independent of bacterial invasionin vitrobut required an intact T3SS-1. In the mouse colitis model, SipA triggered mucosal inflammation in wild-type mice but not in NOD1/NOD2-deficient mice. These findings implicate SipA-driven activation of the NOD1/NOD2 signaling pathway as a mechanism by which the T3SS-1 induces inflammatory responsesin vitroandin vivo.IMPORTANCESalmonella entericaserotype Typhimurium (S. Typhimurium) deploys a type III secretion system (T3SS-1) to induce intestinal inflammation and benefits from the ensuing host response, which enhances growth of the pathogen in the intestinal lumen. However, the mechanisms by which the T3SS-1 triggers inflammatory responses have not been resolved. Here we show that the T3SS-1 effector protein SipA induces NF-κB activation and intestinal inflammation by activating the NOD1/NOD2 signaling pathway. These data suggest that the T3SS-1 escalates innate responses through a SipA-mediated activation of pattern recognition receptors in the host cell cytosol.

scholarly journals Neutrophils Are a Source of Gamma Interferon during Acute Salmonella enterica Serovar Typhimurium Colitis

2014 ◽  
Vol 82 (4) ◽  
pp. 1692-1697 ◽  
Author(s):  
Alanna M. Spees ◽  
Dawn D. Kingsbury ◽  
Tamding Wangdi ◽  
Mariana N. Xavier ◽  
Renée M. Tsolis ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Intestinal Inflammation ◽  
Gamma Interferon ◽  
Content Type ◽  
Inflammatory Monocytes ◽  
Intestinal Lesions ◽  
Serovar Typhimurium ◽  
Cellular Source ◽  
Ifn Γ ◽  
Cecal Mucosa

ABSTRACTGamma interferon (IFN-γ) is an important driver of intestinal inflammation during colitis caused bySalmonella entericaserovar Typhimurium. Here we used the mouse colitis model to investigate the cellular sources of IFN-γ in the cecal mucosa during the acute phase of anS. Typhimurium infection. While IFN-γ staining was detected in T cells, NK cells, and inflammatory monocytes at 2 days after infection, the majority of IFN-γ-positive cells in the cecal mucosa were neutrophils. Furthermore, neutrophil depletion blunted mucosalIfngexpression and reduced the severity of intestinal lesions duringS. Typhimurium infection. We conclude that neutrophils are a prominent cellular source of IFN-γ during the innate phase ofS. Typhimurium-induced colitis.

scholarly journals Differences in Host Cell Invasion and Salmonella Pathogenicity Island 1 Expression between Salmonella enterica Serovar Paratyphi A and NontyphoidalS. Typhimurium

2016 ◽  
Vol 84 (4) ◽  
pp. 1150-1165 ◽  
Author(s):  
Dana Elhadad ◽  
Prerak Desai ◽  
Guntram A. Grassl ◽  
Michael McClelland ◽  
Galia Rahav ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Invasion ◽  
Salmonella Enterica ◽  
Intestinal Inflammation ◽  
Pathogenicity Island ◽  
Effector Proteins ◽  
Host Cells ◽  
Host Cell Invasion ◽  
Content Type ◽  
Microaerobic Conditions

Active invasion into nonphagocytic host cells is central toSalmonella entericapathogenicity and dependent on multiple genes withinSalmonellapathogenicity island 1 (SPI-1). Here, we explored the invasion phenotype and the expression of SPI-1 in the typhoidal serovarS. Paratyphi A compared to that of the nontyphoidal serovarS. Typhimurium. We demonstrate that whileS. Typhimurium is equally invasive under both aerobic and microaerobic conditions,S. Paratyphi A invades only following growth under microaerobic conditions. Transcriptome sequencing (RNA-Seq), reverse transcription-PCR (RT-PCR), Western blot, and secretome analyses established thatS. Paratyphi A expresses much lower levels of SPI-1 genes and secretes lesser amounts of SPI-1 effector proteins thanS. Typhimurium, especially under aerobic growth. Bypassing the native SPI-1 regulation by inducible expression of the SPI-1 activator, HilA, considerably elevated SPI-1 gene expression, host cell invasion, disruption of epithelial integrity, and induction of proinflammatory cytokine secretion byS. Paratyphi A but not byS. Typhimurium, suggesting that SPI-1 expression is naturally downregulated inS. Paratyphi A. Using streptomycin-treated mice, we were able to establish substantial intestinal colonization byS. Paratyphi A and showed moderately higher pathology and intestinal inflammation in mice infected withS. Paratyphi A overexpressinghilA. Collectively, our results reveal unexpected differences in SPI-1 expression betweenS. Paratyphi A andS. Typhimurium, indicate thatS. Paratyphi A host cell invasion is suppressed under aerobic conditions, and suggest that lower invasion in aerobic sites and suppressed expression of immunogenic SPI-1 components contributes to the restrained inflammatory infection elicited byS. Paratyphi A.

Florfenicol Enhances Colonization of Salmonella enterica serovar Enteritidis floR mutant with Major Alterations to the Intestinal Microbiota and Metabolome in Neonatal Chickens

2021 ◽  
Author(s):  
Xueran Mei ◽  
Boheng Ma ◽  
Xiwen Zhai ◽  
Anyun Zhang ◽  
Changwei Lei ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Intestinal Microbiota ◽  
Salmonella Enterica ◽  
Acid Metabolism ◽  
Intestinal Inflammation ◽  
Poultry Production ◽  
Intestinal Colonization ◽  
Gut Colonization ◽  
Linoleic Acid Metabolism

Florfenicol is an important antibiotic commonly used in poultry production to prevent and treat Salmonella infection. However, oral administration of florfenicol may alter the animals’ natural microbiota and metabolome, thereby reducing the intestinal colonization resistance and increasing the susceptibility to Salmonella infection. In this study, we determined the effect of florfenicol (30 mg/kg) on gut colonization of neonatal chickens challenged with Salmonella enterica subsp. enterica serovar Enteritidis ( S. Enteritidis ). We then analyzed the microbial community structure and metabolic profiling of cecal contents using microbial 16S amplicon sequencing and LC-MS untargeted metabolomics, respectively. We also screened the marker metabolites using a multi-omics technique and assessed the effect of these markers on the intestinal colonization S. Enteritidis . Florfenicol administration significantly increased the loads of S. Enteritidis in cecal contents, spleen, and liver, and prolonged the residence of S. Enteritidis . Moreover, florfenicol significantly affected the cecal colony structures, with reduced the abundance of Lactobacillus and Bacteroidetes , and increased the levels of Clostridia , Clostridium and Dorea . The metabolome was greatly influenced by florfenicol administration, and perturbation in metabolic pathways related to linoleic acid metabolism (linoleic acid, conjugated linoleic acid, 12,13-EpOME and 12,13-diHOME) was most prominently detected. We screened conjugated linoleic acid (CLA) and 12,13-diHOME as the marker metabolites, which were highly associated with Lactobacillus , Clostridium and Dorea . Supplementation with CLA maintained intestinal integrity, reduced intestinal inflammation, and accelerated Salmonella clearance from the gut and remission of enteropathy. Whereas, treatment with 12,13-diHOME promoted intestinal inflammation and disrupted the intestinal barrier function to sustain Salmonella infection. Thus, these results highlight that florfenicol alters the intestinal microbiota and metabolism of neonatal chickens, and promotes Salmonella infection mainly by affecting linoleic acid metabolism.

scholarly journals Enteric Salmonellosis Disrupts the Microbial Ecology of the Murine Gastrointestinal Tract

2007 ◽  
Vol 76 (3) ◽  
pp. 907-915 ◽  
Author(s):  
Melissa Barman ◽  
David Unold ◽  
Kathleen Shifley ◽  
Elad Amir ◽  
Kueichun Hung ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Salmonella Enterica ◽  
Time Course ◽  
Intestinal Tract ◽  
Lethal Dose ◽  
Mucosal Immune Response ◽  
Mucosal Inflammation ◽  
Bacterial Number ◽  
Molecular Approaches ◽  
Serovar Typhimurium

ABSTRACT The commensal microbiota protects the murine host from enteric pathogens. Nevertheless, specific pathogens are able to colonize the intestinal tract and invade, despite the presence of an intact biota. Possibly, effective pathogens disrupt the indigenous microbiota, either directly through pathogen-commensal interaction, indirectly via the host mucosal immune response to the pathogen, or by a combination of these factors. This study investigates the effect of peroral Salmonella enterica serovar Typhimurium infection on the intestinal microbiota. Since the majority of the intestinal microbiota cannot be cultured by conventional techniques, molecular approaches using 16S rRNA sequences were applied. Several major bacterial groups were assayed using quantitative PCR. Administration of either the 50% lethal dose (LD50) or 10× LD50 of Salmonella enterica serovar Typhimurium caused changes in the microbiota throughout the intestinal tract over the time course of infection. A 95% decrease in total bacterial number was noted in the cecum and large intestine with 10× LD50 S. enterica serovar Typhimurium challenge at 7 days postinfection, concurrent with gross evidence of diarrhea. In addition, alterations in microbiota composition preceded the onset of diarrhea, suggesting the involvement of pathogen-commensal interactions and/or host responses unrelated to diarrhea. Microbiota alterations were not permanent and reverted to the microbiota of uninfected mice by 1 month postinfection. Infection with a Salmonella pathogenicity island 1 (SPI1) mutant did not result in microbiota alterations, while SPI2 mutant infections triggered partial changes. Neither mutant was capable of prolonged colonization or induction of mucosal inflammation. These data suggest that several Salmonella virulence factors, particularly those involved in the local mucosal host response, are required for disruption of the intestinal ecosystem.

scholarly journals The Actin-Polymerizing Activity of SipA Is Not Essential for Salmonella enterica Serovar Typhimurium-Induced Mucosal Inflammation

2013 ◽  
Vol 81 (5) ◽  
pp. 1541-1549 ◽  
Author(s):  
Dongju Li ◽  
Xueqin Wang ◽  
Lu Wang ◽  
Daoguo Zhou
Keyword(s):  
Inflammatory Response ◽  
Mouse Model ◽  
Salmonella Enterica ◽  
Intestinal Inflammation ◽  
Host Cells ◽  
Bacterial Invasion ◽  
Content Type ◽  
Type Iii ◽  
Serovar Typhimurium ◽  
Mouse Model Of Infection

ABSTRACTSalmonella entericaserovar Typhimurium depends on type III secretion systems to inject effector proteins into host cells to promote bacterial invasion and to induce intestinal inflammation. SipA, a type III effector, is known to play important roles in both the invasion and the elicitation of intestinal inflammation. The actin-modulating activity of SipA has been shown to promoteSalmonellaentry into epithelial cells. To investigate whether the actin-modulating activity of SipA is required for its ability to induce an inflammatory responsein vivo, we generated the SipAK635A E637Wmutant, which is deficient in actin-modulating activity.Salmonellastrains expressing the chromosomal SipAK635A E637Wpoint mutation had reduced invasion abilities but still caused colitis similar to that caused by the wild-type strain in a mouse model of infection. Our data indicate that the SipA actin-polymerizing activity is not essential for the SipA-induced inflammatory response in the mouse model of infection.

scholarly journals Host Transmission of Salmonella enterica Serovar Typhimurium Is Controlled by Virulence Factors and Indigenous Intestinal Microbiota

2007 ◽  
Vol 76 (1) ◽  
pp. 403-416 ◽  
Author(s):  
Trevor D. Lawley ◽  
Donna M. Bouley ◽  
Yana E. Hoy ◽  
Christine Gerke ◽  
David A. Relman ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Disease Transmission ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Virulence Determinants ◽  
Infectious Disease Transmission ◽  
Serovar Typhimurium ◽  
Infection Disease

ABSTRACT Transmission is an essential stage of a pathogen's life cycle and remains poorly understood. We describe here a model in which persistently infected 129X1/SvJ mice provide a natural model of Salmonella enterica serovar Typhimurium transmission. In this model only a subset of the infected mice, termed supershedders, shed high levels (>108 CFU/g) of Salmonella serovar Typhimurium in their feces and, as a result, rapidly transmit infection. While most Salmonella serovar Typhimurium-infected mice show signs of intestinal inflammation, only supershedder mice develop colitis. Development of the supershedder phenotype depends on the virulence determinants Salmonella pathogenicity islands 1 and 2, and it is characterized by mucosal invasion and, importantly, high luminal abundance of Salmonella serovar Typhimurium within the colon. Immunosuppression of infected mice does not induce the supershedder phenotype, demonstrating that the immune response is not the main determinant of Salmonella serovar Typhimurium levels within the colon. In contrast, treatment of mice with antibiotics that alter the health-associated indigenous intestinal microbiota rapidly induces the supershedder phenotype in infected mice and predisposes uninfected mice to the supershedder phenotype for several days. These results demonstrate that the intestinal microbiota plays a critical role in controlling Salmonella serovar Typhimurium infection, disease, and transmissibility. This novel model should facilitate the study of host, pathogen, and intestinal microbiota factors that contribute to infectious disease transmission.

scholarly journals Salmonella enterica in Soils Amended with Heat-Treated Poultry Pellets Survived Longer than Bacteria in Unamended Soils and More Readily Transferred to and Persisted on Spinach

2019 ◽  
Vol 85 (10) ◽  
Author(s):  
Manoj K. Shah ◽  
Rhodel Bradshaw ◽  
Esmond Nyarko ◽  
Eric T. Handy ◽  
Cheryl East ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Slow Release ◽  
Dry Weight ◽  
Plate Count ◽  
Amended Soils ◽  
Content Type ◽  
Slow Release Fertilizer ◽  
Unamended Soil ◽  
Heat Treated ◽  
Mutant Strains

ABSTRACT Untreated biological soil amendments of animal origin (BSAAO) are commonly used as biological fertilizers but can harbor foodborne pathogens like Salmonella enterica, leading to potential transfer from soils to fruits and vegetables intended for human consumption. Heat-treated poultry pellets (HTPP) can provide produce growers with a slow-release fertilizer with a minimized risk of pathogen contamination. Little is known about the impact of HTPP-amended soil on the survival of Salmonella enterica. The contributions of RpoS and formation of viable but nonculturable cells to Salmonella survival in soils are also inadequately understood. We quantified the survival of Salmonella enterica subsp. enterica serovar Newport wild-type (WT) and rpoS-deficient (ΔrpoS mutant) strains in HTPP-amended and unamended soil with or without spinach plants over 91 days using culture and quantitative PCR methods with propidium monoazide (PMA-qPCR). Simulated “splash” transfer of S. Newport from soil to spinach was evaluated at 35 and 63 days postinoculation (dpi). The S. Newport WT and ΔrpoS mutant reached the limit of detection, 1.0 log CFU/g (dry weight), in unamended soil after 35 days, whereas 2 to 4 log CFU/g (dry weight) was observed for both WT and ΔrpoS mutant strains at 91 dpi in HTPP-amended soil. S. Newport levels in soils determined by PMA-qPCR and plate count methods were similar (P > 0.05). HTPP-amended soils supported higher levels of S. Newport transfer to and survival on spinach leaves for longer periods of time than did unamended soils (P < 0.05). Salmonella Newport introduced to HTPP-amended soils survived for longer periods and was more likely to transfer to and persist on spinach plants than was S. Newport introduced to unamended soils. IMPORTANCE Heat-treated poultry pellets (HTPP) often are used by fruit and vegetable growers as a slow-release fertilizer. However, contamination of soil on farms may occur through contaminated irrigation water or scat from wild animals. Here, we show that the presence of HTPP in soil led to increased S. Newport survival in soil and to greater likelihood of its transfer to and survival on spinach plants. There were no significant differences in survival durations of WT and ΔrpoS mutant isolates of S. Newport. The statistically similar populations recovered by plate count and estimated by PMA-qPCR for both strains in the amended and unamended soils in this study indicate that all viable populations of S. Newport in soils were culturable.

scholarly journals Enrofloxacin Shifts Intestinal Microbiota and Metabolic Profiling and Hinders Recovery from Salmonella enterica subsp. enterica Serovar Typhimurium Infection in Neonatal Chickens

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Boheng Ma ◽  
Xueran Mei ◽  
Changwei Lei ◽  
Cui Li ◽  
Yufeng Gao ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Salmonella Enterica ◽  
Amplicon Sequencing ◽  
Treated Group ◽  
Content Type ◽  
16S Amplicon Sequencing ◽  
Serovar Typhimurium ◽  
Metabolite Synthesis ◽  
Chicken Cecum

ABSTRACT Enrofloxacin is an important antibiotic used for prevention and treatment of Salmonella infection in poultry in many countries. However, oral administration of enrofloxacin may lead to the alterations in the microbiota and metabolome in the chicken intestine, thereby reducing colonization resistance to the Salmonella infection. To study the effect of enrofloxacin on Salmonella in the chicken cecum, we used different concentrations of enrofloxacin to feed 1-day-old chickens, followed by oral challenge with Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium). We then explored the distribution pattern of S. Typhimurium in cecum contents in vivo and analyzed the microbial community structure of cecum contents using microbial 16S amplicon sequencing. Untargeted metabolomics was used to explore the gut metabolome on day 14. Faecalibacterium and Anaerostipes, which are closely related to the chicken intestinal metabolome, were screened using a multi-omics technique. The abundance of S. Typhimurium was significantly higher in the enrofloxacin-treated group than in the untreated group, and S. Typhimurium persisted longer. Moreover, the cecal colony structures of the three groups exhibited different characteristics, with Lactobacillus reaching its highest abundance on day 21. Notably, S. Typhimurium infection is known to affect the fecal metabolome of chickens differently. Thus, our results suggested that enrofloxacin and Salmonella infections completely altered the intestinal microbiota and metabolism of chickens. IMPORTANCE In this study, we examined the effects of S. Typhimurium infection and enrofloxacin treatment on the microbiota and metabolite synthesis in chicken cecum, in order to identify target metabolites that may promote S. Typhimurium colonization and aggravate inflammation and to evaluate the important microbiota that may be associated with these metabolites. Our findings may facilitate the use of antibiotics to prevent S. Typhimurium infection.

scholarly journals Coinfection with an Intestinal Helminth Impairs Host Innate Immunity against Salmonella enterica Serovar Typhimurium and Exacerbates Intestinal Inflammation in Mice

2014 ◽  
Vol 82 (9) ◽  
pp. 3855-3866 ◽  
Author(s):  
Libo Su ◽  
Chien-wen Su ◽  
Yujuan Qi ◽  
Guilian Yang ◽  
Mei Zhang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Salmonella Enterica ◽  
Intestinal Inflammation ◽  
Interleukin 10 ◽  
Neutrophil Recruitment ◽  
Intestinal Helminth ◽  
Helminth Parasites ◽  
Content Type ◽  
Infectious Gastroenteritis ◽  
Serovar Typhimurium

ABSTRACTSalmonella entericaserovar Typhimurium is a Gram-negative food-borne pathogen that is a major cause of acute gastroenteritis in humans. The ability of the host to control such bacterial pathogens may be influenced by host immune status and by concurrent infections. Helminth parasites are of particular interest in this context because of their ability to modulate host immune responses and because their geographic distribution coincides with those parts of the world where infectious gastroenteritis is most problematic. To test the hypothesis that helminth infection may negatively regulate host mucosal innate immunity against bacterial enteropathogens, a murine coinfection model was established by using the intestinal nematodeHeligmosomoides polygyrusandS. Typhimurium. We found that mice coinfected withS. Typhimurium andH. polygyrusdeveloped more severe intestinal inflammation than animals infected withS. Typhimurium alone. The enhanced susceptibility toSalmonella-induced intestinal injury in coinfected mice was found to be associated with diminished neutrophil recruitment to the site of bacterial infection that correlated with decreased expression of the chemoattractants CXCL2/macrophage inflammatory protein 2 (MIP-2) and CXCL1/keratinocyte-derived chemokine (KC), poor control of bacterial replication, and exacerbated intestinal inflammation. The mechanism of helminth-induced inhibition of MIP-2 and KC expression involved interleukin-10 (IL-10) and, to a lesser extent, IL-4 and IL-13. Ly6G antibody-mediated depletion of neutrophils reproduced the adverse effects ofH. polygyrusonSalmonellainfection. Our results suggest that impaired neutrophil recruitment is an important contributor to the enhanced severity ofSalmonellaenterocolitis associated with helminth coinfection.

Sign in / Sign up

Export Citation Format

Share Document