scholarly journals Role of CD14 in Responses to Clinical Isolates of Escherichia coli: Effects of K1 Capsule Expression

2007 ◽  
Vol 75 (11) ◽  
pp. 5415-5424 ◽  
Author(s):  
Shalaka Metkar ◽  
Shanjana Awasthi ◽  
Erick Denamur ◽  
Kwang Sik Kim ◽  
Sophie C. Gangloff ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Necrosis Factor Alpha ◽  
Lethal Effects ◽  
E Coli ◽  
Tnf Α ◽  
Positive Isolate ◽  
K1 Capsule

ABSTRACT Severe bacterial infections leading to sepsis or septic shock can be induced by bacteria that utilize different factors to drive pathogenicity and/or virulence, leading to disease in the host. One major factor expressed by all clinical isolates of gram-negative bacteria is lipopolysaccharide (LPS); a second factor expressed by some Escherichia coli strains is a K1 polysaccharide capsule. To determine the role of the CD14 LPS receptor in the pathogenic effects of naturally occurring E. coli, the responses of CD14−/− and CD14+/+ mice to three different isolates of E. coli obtained from sepsis patients were compared; two isolates express both smooth LPS and the K1 antigen, while the third isolate expresses only LPS and is negative for K1. An additional K1-positive isolate obtained from a newborn with meningitis and a K1-negative isogenic mutant of this strain were also used for these studies. CD14−/− mice were resistant to the lethal effects of the K1-negative isolates. This resistance was accompanied by significantly lower levels of systemic tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in these mice than in CD14+/+ mice, enhanced clearance of the bacteria, and significantly fewer additional gross symptoms. In contrast, CD14−/− mice were as sensitive as CD14+/+ mice to the lethal effects of the K1-positive isolates, even though they had significantly lower levels of TNF-α and IL-6 than CD14+/+ mice. These studies show that different bacterial isolates can use distinctly different mechanisms to cause disease and suggest that new, nonantibiotic therapeutics need to be directed against multiple targets.

scholarly journals Efficacy of the Combination of Tachyplesin III and Clarithromycin in Rat Models of Escherichia coli Sepsis

2008 ◽  
Vol 52 (12) ◽  
pp. 4351-4355 ◽  
Author(s):  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Carmela Silvestri ◽  
Wojciech Kamysz ◽  
Fiorenza Orlando ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
Plasma Concentrations ◽  
Necrosis Factor Alpha ◽  
Rat Models ◽  
E Coli ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Isotonic Sodium Chloride

ABSTRACT We investigated the efficacy of tachyplesin III and clarithromycin in two experimental rat models of severe gram-negative bacterial infections. Adult male Wistar rats were given either (i) an intraperitoneal injection of 1 mg/kg Escherichia coli 0111:B4 lipopolysaccharide or (ii) 2 × 1010 CFU of E. coli ATCC 25922. For each model, the animals received isotonic sodium chloride solution, 1 mg/kg tachyplesin III, 50 mg/kg clarithromycin, or 1 mg/kg tachyplesin III combined with 50 mg/kg clarithromycin intraperitoneally. Lethality, bacterial growth in the blood and peritoneum, and the concentrations of endotoxin and tumor necrosis factor alpha (TNF-α) in plasma were evaluated. All the compounds reduced the lethality of the infections compared to that for the controls. Tachyplesin III exerted a strong antimicrobial activity and achieved a significant reduction of endotoxin and TNF-α concentrations in plasma compared to those of the control and clarithromycin-treated groups. Clarithromycin exhibited no antimicrobial activity but had a good impact on endotoxin and TNF-α plasma concentrations. A combination of tachyplesin III and clarithromycin resulted in significant reductions in bacterial counts and proved to be the most-effective treatment in reducing all variables measured.

scholarly journals The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueqin Zhao ◽  
Lei Wang ◽  
Chunling Zhu ◽  
Xiaojing Xia ◽  
Shouping Zhang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
Intestinal Barrier ◽  
Enterohemorrhagic Escherichia Coli ◽  
New Drugs ◽  
Necrosis Factor Alpha ◽  
Intestinal Diseases ◽  
E Coli ◽  
Tnf Α

Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The aim of this study was to investigate whether the antimicrobial peptide mastoparan X (MPX) was effective against E. coli infection. BALB/c mice infected with E. coli by intraperitoneal injection, which represents a sepsis model. In this study, MPX exhibited no toxicity in IPEC-J2 cells and notably suppressed the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) released by E. coli. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, revealing that it protected mice from lethal E. coli infection. Furthermore, MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum. SEM and TEM analyses showed that MPX effectively ameliorated the jejunum damage caused by E. coli and increased the number and length of microvilli. In addition, MPX decreased the expression of IL-2, IL-6, TNF-α, p-p38, and p-p65 in the jejunum and colon. Moreover, MPX increased the expression of ZO-1, occludin, and MUC2 in the jejunum and colon, improved the function of the intestinal barrier, and promoted the absorption of nutrients. This study suggests that MPX is an effective therapeutic agent for E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections.

scholarly journals Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Nalidixic Acid ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Infection Model ◽  
Drug Resistant ◽  
E Coli

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)

scholarly journals Role of Virulence Factors in Resistance of Avian Pathogenic Escherichia coli to Serum and in Pathogenicity

2003 ◽  
Vol 71 (1) ◽  
pp. 536-540 ◽  
Author(s):  
Melha Mellata ◽  
Maryvonne Dho-Moulin ◽  
Charles M. Dozois ◽  
Roy Curtiss ◽  
Peter K. Brown ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Virulence Factors ◽  
Bacterial Resistance ◽  
Serum Resistance ◽  
Temperature Sensitive ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
K1 Capsule

ABSTRACT In chickens, colibacillosis is caused by avian pathogenic Escherichia coli (APEC) via respiratory tract infection. Many virulence factors, including type 1 (F1A) and P (F11) fimbriae, curli, aerobactin, K1 capsule, and temperature-sensitive hemagglutinin (Tsh) and plasmid DNA regions have been associated with APEC. A strong correlation between serum resistance and virulence has been demonstrated, but roles of virulence factors in serum resistance have not been well elucidated. By using mutants of APEC strains TK3, MT78, and χ7122, which belong to serogroups O1, O2, and O78, respectively, we investigated the role of virulence factors in resistance to serum and pathogenicity in chickens. Our results showed that serum resistance is one of the pathogenicity mechanisms of APEC strains. Virulence factors that increased bacterial resistance to serum and colonization of internal organs of infected chickens were O78 lipopolysaccharide of E. coli χ7122 and the K1 capsule of E. coli MT78. In contrast, curli, type 1, and P fimbriae did not appear to contribute to serum resistance. We also showed that the iss gene, which was previously demonstrated to increase resistance to serum in certain E. coli strains, is located on plasmid pAPEC-1 of E. coli χ7122 but does not play a major role in resistance to serum for strain χ7122.

scholarly journals Antimicrobial Peptide MPX Against Escherichia Coli O157:H7 Infection and Inhibiting inflammation, Enhancing Epithelial Barrier and Promoting Nutrient Absorption in the Intestine

2020 ◽  
Author(s):  
Xue qin Zhao ◽  
Lei Wang ◽  
Chun ling Zhu ◽  
Xiao jing Xia ◽  
Shou ping Zhang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
Intestinal Barrier ◽  
Animal Husbandry ◽  
New Drugs ◽  
Inflammatory Factors ◽  
Intestinal Diseases ◽  
E Coli ◽  
Tnf Α

Abstract Background: Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The antimicrobial peptide MPX is extracted from venom and possesses good antibacterial activity against gram-negative bacteria. The aim of this study was to investigate whether MPX could be effective against E. coli infection. Results: In this study, the CCK-8 and lactic dehydrogenase results showed that MPX exhibited no toxicity in IPEC-J2 cells even at a concentration of 128 µg/mL. Furthermore, MPX notably suppressed the levels of IL-2, IL-6, TNF-α, myeloperoxidase and LDH induced by E. coli and reduced inflammation by inhibiting the p-p38-, TLR4- and p-p65-dependent pathways. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing ability of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, and the results showed that MPX could protect mice against lethal infection with E. coli, improve the survival rate of the mice, and reduce the colonization of E. coli in organs and feces. H&E staining showed that MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum, and the effect of MPX was better than that of enrofloxacin. The SEM and TEM results showed that MPX effectively ameliorated the damage caused by E. coli to the jejunum and increased the number and length of microvilli. In addition, real-time PCR revealed that MPX decreased the expression of IL-2, IL-6, and TNF-α in the jejunum and colon. Furthermore, immunohistochemistry and immunofluorescence studies revealed that MPX could reduce the expression of p-p38 and p-p65 in the jejunum, thereby reducing the secretion of inflammatory factors. Moreover, MPX increased the mRNA and protein expression of ZO-1, occludin and MUC2 in the jejunum and colon, improved the function of the intestinal barrier and promoted the absorption of nutrients. Conclusion: This study suggests that MPX may be an effective therapeutic agent against E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections.

scholarly journals CD44 Deficiency Is Associated with Enhanced Escherichia coli-Induced Proinflammatory Cytokine and Chemokine Release by Peritoneal Macrophages

2009 ◽  
Vol 78 (1) ◽  
pp. 115-124 ◽  
Author(s):  
Gerritje J. W. van der Windt ◽  
Cornelis van ′t Veer ◽  
Sandrine Florquin ◽  
Tom van der Poll
Keyword(s):  
Escherichia Coli ◽  
Ex Vivo ◽  
Peritoneal Macrophages ◽  
Cellular Adhesion ◽  
Autologous Serum ◽  
Blood Leukocytes ◽  
Necrosis Factor Alpha ◽  
Altered Expression ◽  
E Coli ◽  
Tnf Α

ABSTRACT CD44 is involved in several immune responses, such as cellular adhesion, migration, proliferation, and activation. Peritonitis is an important cause of sepsis, and Escherichia coli is one of the major pathogens involved therein. We sought to determine the role of CD44 in the host response to E. coli-induced abdominal sepsis and to assess the function of CD44 in the activation of primary peritoneal macrophages by E. coli or lipopolysaccharide (LPS) purified from this bacterium by using wild-type (WT) and CD44 knockout (KO) mice. CD44 KO mice already demonstrated enhanced CXC chemokine levels in peritoneal lavage fluid at 6 h after infection, whereas tumor necrosis factor alpha (TNF-α) and interleukin-6 levels were elevated at 20 h postinfection. In line with this, CD44 KO mouse peritoneal macrophages released more TNF-α and macrophage inflammatory protein 2 (MIP-2) than did WT cells upon stimulation with E. coli or LPS in the presence of autologous serum. In contrast, plasma TNF-α levels were lower in CD44 KO mice and CD44 KO blood leukocytes secreted similar amounts of TNF-α and MIP-2 upon ex vivo incubation with E. coli or LPS. The proinflammatory phenotype of CD44 KO macrophages was not associated with an altered expression of inhibitors of Toll-like receptor signaling, whereas it could be partially reversed by addition of WT serum. CD44 deficiency did not impact on leukocyte recruitment into the peritoneal cavity or organ failure. These data suggest that CD44 differentially influences cytokine and chemokine release by different leukocyte subsets.

scholarly journals Effects of a Mutation in thegyrAGene on the Virulence of Uropathogenic Escherichia coli

2015 ◽  
Vol 59 (8) ◽  
pp. 4662-4668 ◽  
Author(s):  
Javier Sánchez-Céspedes ◽  
Emma Sáez-López ◽  
N. Frimodt-Møller ◽  
Jordi Vila ◽  
Sara M. Soto
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Dna Supercoiling ◽  
Uropathogenic Escherichia Coli ◽  
Topoisomerase Iv ◽  
Content Type ◽  
E Coli ◽  
Type Gene ◽  
Encoding Genes

ABSTRACTFluoroquinolones are among the drugs most extensively used for the treatment of bacterial infections in human and veterinary medicine. Resistance to quinolones can be chromosome or plasmid mediated. The chromosomal mechanism of resistance is associated with mutations in the DNA gyrase- and topoisomerase IV-encoding genes and mutations in regulatory genes affecting different efflux systems, among others. We studied the role of the acquisition of a mutation in thegyrAgene in the virulence and protein expression of uropathogenicEscherichia coli(UPEC). The HC14366M strain carrying a mutation in thegyrAgene (S83L) was found to lose the capacity to cause cystitis and pyelonephritis mainly due to a decrease in the expression of thefimA,papA,papB, andompAgenes. The levels of expression of thefimA,papB, andompAgenes were recovered on complementing the strain with a plasmid containing thegyrAwild-type gene. However, only a slight recovery was observed in the colonization of the bladder in the GyrA complement strain compared to the mutant strain in a murine model of ascending urinary tract infection. In conclusion, a mutation in thegyrAgene of uropathogenicE. colireduced the virulence of the bacteria, likely in association with the effect of DNA supercoiling on the expression of several virulence factors and proteins, thereby decreasing their capacity to cause cystitis and pyelonephritis.

scholarly journals The Antimalarial Artemisinin Synergizes with Antibiotics To Protect against Lethal Live Escherichia coli Challenge by Decreasing Proinflammatory Cytokine Release

2006 ◽  
Vol 50 (7) ◽  
pp. 2420-2427 ◽  
Author(s):  
Jun Wang ◽  
Hong Zhou ◽  
Jiang Zheng ◽  
Juan Cheng ◽  
Wei Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Sensor Technology ◽  
Dependent Manner ◽  
Cpg Odn ◽  
Lethal Challenge ◽  
Necrosis Factor Alpha ◽  
E Coli ◽  
Tlr4 Mrna ◽  
Tnf Α ◽  
Anti Inflammatory

ABSTRACT In the present study artemisinin (ART) was found to have potent anti-inflammatory effects in animal models of sepsis induced by CpG-containing oligodeoxy-nucleotides (CpG ODN), lipopolysaccharide (LPS), heat-killed Escherichia coli 35218 or live E. coli. Furthermore, we found that ART protected mice from a lethal challenge by CpG ODN, LPS, or heat-killed E. coli in a dose-dependent manner and that the protection was related to a reduction in serum tumor necrosis factor alpha (TNF-α). More significantly, the administration of ART together with ampicillin or unasyn (a complex of ampicillin and sulbactam) decreased mortality from 100 to 66.7% or 33.3%, respectively, in mice subjected to a lethal live E. coli challenge. Together with the observation that ART alone does not inhibit bacterial growth, this result suggests that ART protection is achieved as a result of its anti-inflammatory activity rather than an antimicrobial effect. In RAW264.7 cells, pretreatment with ART potently inhibited TNF-α and interleukin-6 release induced by CpG ODN, LPS, or heat-killed E. coli in a dose- and time-dependent manner. Experiments utilizing affinity sensor technology revealed no direct binding of ART with CpG ODN or LPS. Flow cytometry further showed that ART did not alter binding of CpG ODN to cell surfaces or the internalization of CpG ODN. In addition, upregulated levels of TLR9 and TLR4 mRNA were not attenuated by ART treatment. ART treatment did, however, block the NF-κB activation induced by CpG ODN, LPS, or heat-killed E. coli. These findings provide compelling evidence that ART may be an important potential drug for sepsis treatment.

scholarly journals Prc Contributes to Escherichia coli Evasion of Classical Complement-Mediated Serum Killing

2012 ◽  
Vol 80 (10) ◽  
pp. 3399-3409 ◽  
Author(s):  
Chin-Ya Wang ◽  
Shainn-Wei Wang ◽  
Wen-Chun Huang ◽  
Kwang Sik Kim ◽  
Nan-Shan Chang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Membrane Attack Complex ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Serum Killing ◽  
High Level ◽  
Classical Complement

ABSTRACTEscherichia coliis a common Gram-negative organism that causes bacteremia. Prc, a bacterial periplasmic protease, and its homologues are known to be involved in the pathogenesis of Gram-negative bacterial infections. The present study examined the role of Prc inE. colibacteremia and characterized the ability of theprcmutant of the pathogenicE. colistrain RS218 to cause bacteremia and survive in human serum. Theprcmutant of RS218 exhibited a decreased ability to cause a high level of bacteremia and was more sensitive to serum killing than strain RS218. This sensitivity was due to the mutant's decreased ability to avoid the activation of the antibody-dependent and -independent classical complement cascades as well as its decreased resistance to killing mediated by the membrane attack complex, the end product of complement system activation. The demonstration of Prc in the evasion of classical complement-mediated serum killing of pathogenicE. colimakes this factor a potential target for the development of therapeutic and preventive measures againstE. colibacteremia.

scholarly journals Evaluation of a Method Using Three Genomic Guided Escherichia coli Markers for Phylogenetic Typing of E. coli Isolates of Various Genetic Backgrounds

2015 ◽  
Vol 53 (6) ◽  
pp. 1848-1853 ◽  
Author(s):  
Kouta Hamamoto ◽  
Shuhei Ueda ◽  
Yoshimasa Yamamoto ◽  
Itaru Hirai
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Phylogenetic Trees ◽  
Genetic Relationships ◽  
Clinical Isolates ◽  
Typing Method ◽  
Content Type ◽  
E Coli ◽  
Phylogenetic Grouping ◽  
Typing Methods

Genotyping and characterization of bacterial isolates are essential steps in the identification and control of antibiotic-resistant bacterial infections. Recently, one novel genotyping method using three genomic guidedEscherichia colimarkers (GIG-EM),dinG,tonB, and dipeptide permease (DPP), was reported. Because GIG-EM has not been fully evaluated using clinical isolates, we assessed this typing method with 72E. colicollection of reference (ECOR) environmentalE. colireference strains and 63E. coliisolates of various genetic backgrounds. In this study, we designated 768 bp ofdinG, 745 bp oftonB, and 655 bp of DPP target sequences for use in the typing method. Concatenations of the processed marker sequences were used to draw GIG-EM phylogenetic trees.E. coliisolates with identical sequence types as identified by the conventional multilocus sequence typing (MLST) method were localized to the same branch of the GIG-EM phylogenetic tree. Sixteen clinicalE. coliisolates were utilized as test isolates without prior characterization by conventional MLST and phylogenetic grouping before GIG-EM typing. Of these, 14 clinical isolates were assigned to a branch including only isolates of a pandemic clone,E. coliB2-ST131-O25b, and these results were confirmed by conventional typing methods. Our results suggested that the GIG-EM typing method and its application to phylogenetic trees might be useful tools for the molecular characterization and determination of the genetic relationships amongE. coliisolates.

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