scholarly journals Streptomycin-Induced Inflammation Enhances Escherichia coli Gut Colonization Through Nitrate Respiration

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Alanna M. Spees ◽  
Tamding Wangdi ◽  
Christopher A. Lopez ◽  
Dawn D. Kingsbury ◽  
Mariana N. Xavier ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Microbial Community ◽  
Intestinal Inflammation ◽  
Anaerobic Bacteria ◽  
Nitrate Respiration ◽  
Colonization Resistance ◽  
Content Type ◽  
E Coli ◽  
Gut Colonization ◽  
Facultative Anaerobic Bacteria

ABSTRACTTreatment with streptomycin enhances the growth of human commensalEscherichia coliisolates in the mouse intestine, suggesting that the resident microbial community (microbiota) can inhibit the growth of invading microbes, a phenomenon known as “colonization resistance.” However, the precise mechanisms by which streptomycin treatment lowers colonization resistance remain obscure. Here we show that streptomycin treatment rendered mice more susceptible to the development of chemically induced colitis, raising the possibility that the antibiotic might lower colonization resistance by changing mucosal immune responses rather than by preventing microbe-microbe interactions. Investigation of the underlying mechanism revealed a mild inflammatory infiltrate in the cecal mucosa of streptomycin-treated mice, which was accompanied by elevated expression ofNos2, the gene that encodes inducible nitric oxide synthase. In turn, this inflammatory response enhanced the luminal growth ofE. coliby nitrate respiration in aNos2-dependent fashion. These data identify low-level intestinal inflammation as one of the factors responsible for the loss of resistance toE. colicolonization after streptomycin treatment.IMPORTANCEOur intestine is host to a complex microbial community that confers benefits by educating the immune system and providing niche protection. Perturbation of intestinal communities by streptomycin treatment lowers “colonization resistance” through unknown mechanisms. Here we show that streptomycin increases the inflammatory tone of the intestinal mucosa, thereby making the bowel more susceptible to dextran sulfate sodium treatment and boosting theNos2-dependent growth of commensalEscherichia coliby nitrate respiration. These data point to the generation of alternative electron acceptors as a by-product of the inflammatory host response as an important factor responsible for lowering resistance to colonization by facultative anaerobic bacteria such asE. coli.

scholarly journals Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Stephanie A. Cevallos ◽  
Jee-Yon Lee ◽  
Connor R. Tiffany ◽  
Austin J. Byndloss ◽  
Luana Johnston ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Risk Factor ◽  
Microbial Community ◽  
Intestinal Inflammation ◽  
Aerobic Respiration ◽  
Content Type ◽  
E Coli ◽  
Chemically Induced ◽  
Underlying Mechanisms

ABSTRACT Intestinal inflammation is a risk factor for colorectal cancer formation, but the underlying mechanisms remain unknown. Here, we investigated whether colitis alters the colonic microbiota to enhance its cancer-inducing activity. Colitis increased epithelial oxygenation in the colon of mice and drove an expansion of Escherichia coli within the gut-associated microbial community through aerobic respiration. An aerobic expansion of colibactin-producing E. coli was required for the cancer-inducing activity of this pathobiont in a mouse model of colitis-associated colorectal cancer formation. We conclude that increased epithelial oxygenation in the colon is associated with an expansion of a prooncogenic driver species, thereby increasing the cancer-inducing activity of the microbiota. IMPORTANCE One of the environmental factors important for colorectal cancer formation is the gut microbiota, but the habitat filters that control its cancer-inducing activity remain unknown. Here, we show that chemically induced colitis elevates epithelial oxygenation in the colon, thereby driving an expansion of colibactin-producing Escherichia coli, a prooncogenic driver species. These data suggest that elevated epithelial oxygenation is a potential risk factor for colorectal cancer formation because the consequent changes in the gut habitat escalate the cancer-inducing activity of the microbiota.

scholarly journals One-Carbon Metabolic Pathway Rewiring in Escherichia coli Reveals an Evolutionary Advantage of 10-Formyltetrahydrofolate Synthetase (Fhs) in Survival under Hypoxia

2014 ◽  
Vol 197 (4) ◽  
pp. 717-726 ◽  
Author(s):  
Shivjee Sah ◽  
Srinivas Aluri ◽  
Kervin Rex ◽  
Umesh Varshney
Keyword(s):  
Escherichia Coli ◽  
Anaerobic Bacteria ◽  
High Capacity ◽  
Natural Occurrence ◽  
Content Type ◽  
E Coli ◽  
Formyltetrahydrofolate Synthetase ◽  
Facultative Anaerobic Bacteria

In cells,N10-formyltetrahydrofolate (N10-fTHF) is required for formylation of eubacterial/organellar initiator tRNA and purine nucleotide biosynthesis. Biosynthesis ofN10-fTHF is catalyzed by 5,10-methylene-tetrahydrofolate dehydrogenase/cyclohydrolase (FolD) and/or 10-formyltetrahydrofolate synthetase (Fhs). All eubacteria possess FolD, but some possess both FolD and Fhs. However, the reasons for possessing Fhs in addition to FolD have remained unclear. We usedEscherichia coli, which naturally lacksfhs, as our model. We show that inE. coli, the essential function offolDcould be replaced byClostridium perfringensfhswhen it was provided on a medium-copy-number plasmid or integrated as a single-copy gene in the chromosome. Thefhs-supportedfolDdeletion (ΔfolD) strains grow well in a complex medium. However, these strains require purines and glycine as supplements for growth in M9 minimal medium. Thein vivolevels ofN10-fTHF in the ΔfolDstrain (supported by plasmid-bornefhs) were limiting despite the high capacity of the available Fhs to synthesizeN10-fTHFin vitro. Auxotrophy for purines could be alleviated by supplementing formate to the medium, and that for glycine was alleviated by engineering THF import into the cells. The ΔfolDstrain (harboringfhson the chromosome) showed a high NADP+-to-NADPH ratio and hypersensitivity to trimethoprim. The presence offhsinE. coliwas disadvantageous for its aerobic growth. However, under hypoxia,E. colistrains harboringfhsoutcompeted those lacking it. The computational analysis revealed a predominant natural occurrence offhsin anaerobic and facultative anaerobic bacteria.

scholarly journals Inflammation-Induced Acid Tolerance GenesgadABin Luminal Commensal Escherichia coli Attenuate Experimental Colitis

2013 ◽  
Vol 81 (10) ◽  
pp. 3662-3671 ◽  
Author(s):  
Sandrine Tchaptchet ◽  
Ting-Jia Fan ◽  
Laura Goeser ◽  
Alexi Schoenborn ◽  
Ajay S. Gulati ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Acid Tolerance ◽  
Experimental Colitis ◽  
Intestinal Epithelial ◽  
Content Type ◽  
E Coli ◽  
Chronic Intestinal Inflammation

ABSTRACTDysregulated immune responses to commensal intestinal bacteria, includingEscherichia coli, contribute to the development of inflammatory bowel diseases (IBDs) and experimental colitis. Reciprocally,E. coliresponds to chronic intestinal inflammation by upregulating expression of stress response genes, includinggadAandgadB. GadAB encode glutamate decarboxylase and protectE. colifrom the toxic effects of low pH and fermentation acids, factors present in the intestinal lumen in patients with active IBDs. We hypothesized thatE. coliupregulatesgadABduring inflammation to enhance its survival and virulence. Using real-time PCR, we determinedgadABexpression in luminalE. colifrom ex-germfree wild-type (WT) and interleukin-10 (IL-10) knockout (KO) (IL-10−/−) mice selectively colonized with a commensalE. coliisolate (NC101) that causes colitis in KO mice in isolation or in combination with 7 other commensal intestinal bacterial strains.E. colisurvival and host inflammatory responses were measured in WT and KO mice colonized with NC101 or a mutant lacking thegadABgenes (NC101ΔgadAB). The susceptibility of NC101 and NC101ΔgadABto killing by host antimicrobial peptides and their translocation across intestinal epithelial cells were evaluated using bacterial killing assays and transwell experiments, respectively. We show that expression ofgadABin luminalE. coliincreases proportionately with intestinal inflammation in KO mice and enhances the susceptibility of NC101 to killing by the host antimicrobial peptide cryptdin-4 but decreases bacterial transmigration across intestinal epithelial cells, colonic inflammation, and mucosal immune responses. Chronic intestinal inflammation upregulates acid tolerance pathways in commensalE. coliisolates, which, contrary to our original hypothesis, limits their survival and colitogenic potential. Further investigation of microbial adaptation to immune-mediated inflammation may provide novel insights into the pathogenesis and treatment of IBDs.

scholarly journals Escherichia coli Pathotypes Occupy Distinct Niches in the Mouse Intestine

2014 ◽  
Vol 82 (5) ◽  
pp. 1931-1938 ◽  
Author(s):  
Jessica P. Meador ◽  
Matthew E. Caldwell ◽  
Paul S. Cohen ◽  
Tyrrell Conway
Keyword(s):  
Escherichia Coli ◽  
Infection Process ◽  
Treated Mouse ◽  
Colonization Resistance ◽  
Content Type ◽  
E Coli ◽  
Similar Strategy ◽  
Mouse Intestine

ABSTRACTSince the first step of the infection process is colonization of the host, it is important to understand howEscherichia colipathogens successfully colonize the intestine. We previously showed that enterohemorrhagic O157:H7 strainE. coliEDL933 colonizes a niche in the streptomycin-treated mouse intestine that is distinct from that of human commensal strains, which explains howE. coliEDL933 overcomes colonization resistance imparted by some, but not all, commensalE. colistrains. Here we sought to determine if otherE. colipathogens use a similar strategy. We found that uropathogenicE. coliCFT073 and enteropathogenicE. coliE2348/69 occupy intestinal niches that are distinct from that ofE. coliEDL933. In contrast, two enterohemorrhagic strains,E. coliEDL933 andE. coliSakai, occupy the same niche, suggesting that strategies to prevent colonization by a given pathotype should be effective against other strains of the same pathotype. However, we found that a combination of commensalE. colistrains that can prevent colonization byE. coliEDL933 did not prevent colonization byE. coliCFT073 orE. coliE2348/69. Our results indicate that development of probiotics to target multipleE. colipathotypes will be problematic, as the factors that govern niche occupation and hence stable colonization vary significantly among strains.

scholarly journals Oral Tolerance Failure upon Neonatal Gut Colonization with Escherichia coli Producing the Genotoxin Colibactin

2015 ◽  
Vol 83 (6) ◽  
pp. 2420-2429 ◽  
Author(s):  
Thomas Secher ◽  
Delphine Payros ◽  
Camille Brehin ◽  
Michele Boury ◽  
Claude Watrin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Oral Tolerance ◽  
Developed Countries ◽  
Phylogenetic Group ◽  
Delayed Type Hypersensitivity ◽  
Dominant Group ◽  
Content Type ◽  
E Coli ◽  
Gut Colonization ◽  
Immune Mediated

The intestinal barrier controls the balance between tolerance and immunity to luminal antigens. When this finely tuned equilibrium is deregulated, inflammatory disorders can occur. There is a concomitant increase, in urban populations of developed countries, of immune-mediated diseases along with a shift inEscherichia colipopulation from the declining phylogenetic group A to the newly dominant group B2, including commensal strains producing a genotoxin called colibactin that massively colonized the gut of neonates. Here, we showed that mother-to-offspring early gut colonization by colibactin-producingE. coliimpairs intestinal permeability and enhances the transepithelial passage of luminal antigen, leading to an increased immune activation. Functionally, this was accompanied by a dramatic increase in local and systemic immune responses against a fed antigen, decreased regulatory T cell population, tolerogenic dendritic cells, and enhanced mucosal delayed-type hypersensitivity response. Conversely, the abolition of colibactin expression by mutagenesis abrogates the alteration of oral tolerance induced by neonatal colonization byE. coli. In conclusion, the vertical colonization byE. coliproducing the genotoxin colibactin enhances intestinal translocation and subsequently alters oral tolerance. Thus, early colonization byE. colifrom the newly dominant phylogenetic group B2, which produces colibactin, may represent a risk factor for the development of immune-mediated diseases.

scholarly journals Suppression of Clostridium difficile in the Gastrointestinal Tracts of Germfree Mice Inoculated with a Murine Isolate from the Family Lachnospiraceae

2012 ◽  
Vol 80 (11) ◽  
pp. 3786-3794 ◽  
Author(s):  
Angela E. Reeves ◽  
Mark J. Koenigsknecht ◽  
Ingrid L. Bergin ◽  
Vincent B. Young
Keyword(s):  
Microbial Community ◽  
Clostridium Difficile ◽  
Clinical Signs ◽  
Colonization Resistance ◽  
Content Type ◽  
E Coli ◽  
Mild Disease ◽  
Treatment And Prevention ◽  
The Family ◽  
Indigenous Microbial Community

ABSTRACTThe indigenous microbial community of the gastrointestinal (GI) tract determines susceptibility toClostridium difficilecolonization and disease. Previous studies have demonstrated that antibiotic-treated mice challenged withC. difficileeither developed rapidly lethalC. difficileinfection or were stably colonized with mild disease. The GI microbial community of animals with mild disease was dominated by members of the bacterial familyLachnospiraceae, while the gut community in moribund animals had a predominance ofEscherichia coli. We investigated the roles of murineLachnospiraceaeandE. colistrains in colonization resistance againstC. difficilein germfree mice. MurineLachnospiraceaeandE. coliisolates were cultured from wild-type mice. The ability of each of these isolates to interfere withC. difficilecolonization was tested by precolonizing germfree mice with these bacteria 4 days prior to experimentalC. difficilechallenge. Mice precolonized with a murineLachnospiraceaeisolate, but not those colonized withE. coli, had significantly decreasedC. difficilecolonization, lower intestinal cytotoxin levels and exhibited less severe clinical signs and colonic histopathology. Infection of germfree mice or mice precolonized withE. coliwithC. difficilestrain VPI 10463 was uniformly fatal by 48 h, but only 20% mortality was seen at 2 days in mice precolonized with theLachnospiraceaeisolate prior to challenge with VPI 10463. These findings confirm that a single component of the GI microbiota, a murineLachnospiraceaeisolate, could partially restore colonization resistance againstC. difficile. Further study of the members within theLachnospiraceaefamily could lead to a better understanding of mechanisms of colonization resistance againstC. difficileand novel therapeutic approaches for the treatment and prevention ofC. difficileinfection.

scholarly journals RESISTANCE OF Escherichia coli FROM RECTAL SWAB CULTURE IN HEMATO-ONCOLOGY WARDS, DR. SOETOMO HOSPITAL, SURABAYA

2016 ◽  
Vol 51 (3) ◽  
pp. 193
Author(s):  
Rahmi Rusanti ◽  
IGAA Putri Sri Rejeki
Keyword(s):  
Escherichia Coli ◽  
Pediatric Patients ◽  
Rectal Swab ◽  
Anaerobic Bacteria ◽  
Secondary Data ◽  
E Coli ◽  
Rectal Swabs ◽  
Infection Resistance ◽  
Common Etiology ◽  
Facultative Anaerobic Bacteria

Malignant hematology patients in the hospital are particularly susceptible to infection associated with endogenous microorganism originating from their own body. The most common etiology of infection is bacteria from gastrointestinal tract. Escherichia coli is a gram-negative facultative anaerobic bacteria, and part of the intestinal normal flora. However, E. coli is the most common cause of nosocomial infection. Resistance of E. coli to antibiotics has been widely reported. The aim of this study was to identify the development of antibiotic resistant properties of Escherichia coli from rectal swab of malignant hematology pediatric patients. A descriptive study of collected secondary data on sensitivity test results was done in the hematology-oncology pediatric ward, Dr. Soetomo Hospital from October 2012 to March 2013. There were 20 results of antibiotic susceptibility testing on positive Escherichia coli cultures from rectal swabs. The highest resistance levels were found towards cotrimoxazol, ampicillin sulbactam and cefotaxime. Escherichia coli with extended-spectrum b-lactamase (ESBL) was also found. Escherichia coli from rectal swabs of malignant hematology pediatric patients were shown to be resistant to cotrimoxazol, ampicillin sulbactam and ampicillin.

scholarly journals An Escherichia coli O157-Specific Engineered Pyocin Prevents and Ameliorates Infection by E. coli O157:H7 in an Animal Model of Diarrheal Disease

2011 ◽  
Vol 55 (12) ◽  
pp. 5469-5474 ◽  
Author(s):  
Jennifer M. Ritchie ◽  
Jennifer L. Greenwich ◽  
Brigid M. Davis ◽  
Roderick T. Bronson ◽  
Dana Gebhart ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Diarrheal Disease ◽  
Intestinal Inflammation ◽  
Rabbit Model ◽  
Prophylactic Regimen ◽  
Content Type ◽  
Fecal Shedding ◽  
E Coli ◽  
Food Borne ◽  
Enteric Infections

ABSTRACTAvR2-V10.3 is an engineered R-type pyocin that specifically killsEscherichia coliO157, an enteric pathogen that is a major cause of food-borne diarrheal disease. New therapeutics to counteractE. coliO157 are needed, as currently available antibiotics can exacerbate the consequences of infection. We show here that orogastric administration of AvR2-V10.3 can prevent or ameliorateE. coliO157:H7-induced diarrhea and intestinal inflammation in an infant rabbit model of infection when the compound is administered either in a postexposure prophylactic regimen or after the onset of symptoms. Notably, administration of AvR2-V10.3 also reduces bacterial carriage and fecal shedding of this pathogen. Our findings support the further development of pathogen-specific R-type pyocins as a way to treat enteric infections.

scholarly journals Dextran Sodium Sulfate-Induced Inflammation Alters the Expression of Proteins by Intestinal Escherichia coli Strains in a Gnotobiotic Mouse Model

2011 ◽  
Vol 78 (5) ◽  
pp. 1513-1522 ◽  
Author(s):  
Sara Schumann ◽  
Carl Alpert ◽  
Wolfram Engst ◽  
Gunnar Loh ◽  
Michael Blaut
Keyword(s):  
Escherichia Coli ◽  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Dextran Sodium Sulfate ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Uncharacterized Protein ◽  
Fermentation Products ◽  
Content Type ◽  
E Coli

ABSTRACTTo identifyEscherichia coliproteins involved in adaptation to intestinal inflammation, mice were monoassociated with the colitogenicE. colistrain UNC or with the probioticE. colistrain Nissle. Intestinal inflammation was induced by treating the mice with 3.5% dextran sodium sulfate (DSS). Differentially expressed proteins inE. colistrains collected from cecal contents were identified by 2-dimensional difference gel electrophoresis. In both strains, acute inflammation led to the downregulation of pathways involved in carbohydrate breakdown and energy generation. Accordingly, DSS-treated mice had lower concentrations of bacterial fermentation products in their cecal contents than control mice. Differentially expressed proteins also included the Fe-S cluster repair protein NfuA, the tryptophanase TnaA, and the uncharacterized protein YggE. NfuA expression was 3-fold higher inE. colistrains from DSS-treated than from control mice. Reporter experiments confirmed the induction ofnfuAin response to iron deprivation, mimicking Fe-S cluster destruction by inflammation. YggE expression, which has been reported to reduce the intracellular level of reactive oxygen species, was 4- to 8-fold higher inE. coliNissle than inE. coliUNC. This was confirmed byin vitroreporter gene assays indicating that Nissle is better equipped to cope with oxidative stress than UNC. Nissle isolated from DSS-treated and control mice had TnaA levels 4- to 7-fold-higher than those of UNC. Levels of indole resulting from the TnaA reaction were higher in control animals associated withE. coliNissle. Because of its anti-inflammatory effect, indole is hypothesized to be involved in the extension of the remission phase in ulcerative colitis described forE. coliNissle.

scholarly journals Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli

2017 ◽  
Vol 83 (17) ◽  
Author(s):  
Tingting Ju ◽  
Yasmeen Shoblak ◽  
Yanhua Gao ◽  
Kaiyuan Yang ◽  
Janelle Fouhse ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Gut Microbiota ◽  
Host Response ◽  
Intestinal Inflammation ◽  
Antibiotic Administration ◽  
Microbiota Composition ◽  
Microbial Composition ◽  
Content Type ◽  
E Coli ◽  
Key Factor

ABSTRACT Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota.

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