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 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 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 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 The Mechanism of Antimicrobial Peptide MPX against Enterohemorrhagic Escherichia coli in Vitro

2021 ◽  
pp. 18-24
Author(s):  
Ксюєцінь Дзяо ◽  
Ганна Фотіна ◽  
Лей Ванг ◽  
Цзяньхе Ху
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Bactericidal Activity ◽  
Enterohemorrhagic Escherichia Coli ◽  
New Drugs ◽  
Plate Count ◽  
E Coli ◽  
Facultative Anaerobic Bacteria ◽  
The Impact

Escherichia coli is a facultative anaerobic bacteria that exists in the gastrointestinal tract of humans and animals. It can cause diarrhea, enteritis, destruction of the host's intestinal barrier, and intestinal microecological disturbances.  In recent years, due to the abuse of traditional antibiotics, a variety of drug-resistant strains and super bacteria have emerged in an endless stream. Therefore, there is an urgent need to find new alternatives to antibiotics. Antimicrobial peptides are a type of small peptides produced when organisms resist the invasion of foreign microorganisms. They are considered to be the best alternative to antibiotics which has become a research hotspot in recent years. The antimicrobial peptide MPX is extracted from wasp venom and has a good bactericidal effect on many bacteria. To explore the effect of MPX against E. coli. The function of MPX against E. coli was detected by MIC, plate count, propidium iodide, NPN and DiSC3(5) permeability testing, immunofluorescence microscope observation, and the impact of MPX stability by temperature, pH, ion. In this study, the results found that MPX has good antibacterial activity against E. coli, and the minimum inhibitory concentration (MIC) was 31.25 ug/mL. MPX bactericidal kinetics study found that MPX had good bactericidal activity within 6 hours. Bacterial permeability studies have shown that MPX could increase the permeability of bacteria, leading to an increase in the protein content of the bacterial supernatant. In addition, NPN, PI and DiSC3(5) results showed that the fluorescence value was positively correlated with MPX. The stability test of MPX found that salt ions, temperature, pH, etc. have a slight influence on its effect. In addition, scanning electron microscopy results showed that the bacteria became smaller and the contents leaked after the action of MPX. The above results showed that MPX has a good bactericidal activity in vitro, laying the foundation for the development of new drugs for the treatment of bacterial infections.

scholarly journals Interaction of Antimicrobial Peptide Temporin L with Lipopolysaccharide In Vitro and in Experimental Rat Models of Septic Shock Caused by Gram-Negative Bacteria

2006 ◽  
Vol 50 (7) ◽  
pp. 2478-2486 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Federico Mocchegiani ◽  
Fiorenza Orlando ◽  
...  
Keyword(s):  
Septic Shock ◽  
Antimicrobial Peptide ◽  
Gram Negative Bacteria ◽  
Amphibian Skin ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Rat Models ◽  
E Coli ◽  
Tnf Α

ABSTRACT Sepsis remains a major cause of morbidity and mortality in hospitalized patients, despite intense efforts to improve survival. The primary lead for septic shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria. For these reasons, the quest for compounds with antiendotoxin properties is actively pursued. We investigated the efficacy of the amphibian skin antimicrobial peptide temporin L in binding Escherichia coli LPS in vitro and counteracting its effects in vivo. Temporin L strongly bound to purified E. coli LPS and lipid A in vitro, as proven by fluorescent displacement assay, and readily penetrated into E. coli LPS monolayers. Furthermore, the killing activity of temporin L against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide's affinity for endotoxin. Antimicrobial assays showed that temporin L interacted synergistically with the clinically used β-lactam antibiotics piperacillin and imipenem. Therefore, we characterized the activity of temporin L when combined with imipenem and piperacillin in the prevention of lethality in two rat models of septic shock, measuring bacterial growth in blood and intra-abdominal fluid, endotoxin and tumor necrosis factor alpha (TNF-α) concentrations in plasma, and lethality. With respect to controls and single-drug treatments, the simultaneous administration of temporin L and β-lactams produced the highest antimicrobial activities and the strongest reduction in plasma endotoxin and TNF-α levels, resulting in the highest survival rates.

scholarly journals Effects of Antimicrobial Peptide Microcin C7 on Growth Performance, Immune and Intestinal Barrier Functions, and Cecal Microbiota of Broilers

2022 ◽  
Vol 8 ◽  
Author(s):  
Ziqi Dai ◽  
Lijun Shang ◽  
Fengming Wang ◽  
Xiangfang Zeng ◽  
Haitao Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Growth Performance ◽  
Intestinal Barrier ◽  
Basal Diet ◽  
Immune Functions ◽  
Serum Cytokine ◽  
Tnf Α ◽  
Cecal Microbiota

Microcin C7 is an antimicrobial peptide produced by Escherichia coli, composed of a heptapeptide with a modified adenosine monophosphate. This study was performed to evaluate the effects of Microcin C7 as a potential substrate to traditional antibiotics on growth performance, immune functions, intestinal barrier, and cecal microbiota of broilers. In the current study, 300 healthy Arbor Acres broiler chicks were randomly assigned to one of five treatments including a corn–soybean basal diet and basal diet supplemented with antibiotic or 2, 4, and 6 mg/kg Microcin C7. Results showed that Microcin C7 significantly decreased the F/G ratio of broilers; significantly increased the levels of serum cytokine IL-10, immunoglobulins IgG and IgM, and ileal sIgA secretion; significantly decreased the level of serum cytokine TNF-α. Microcin C7 significantly increased villus height and V/C ratio and significantly decreased crypt depth in small intestine of broilers. Microcin C7 significantly increased gene expression of tight junction protein Occludin and ZO-1 and significantly decreased gene expression of pro-inflammatory and chemokine TNF-α, IL-8, IFN-γ, Toll-like receptors TLR2 and TLR4, and downstream molecular MyD88 in the jejunum of broilers. Microcin C7 significantly increased the number of Lactobacillus and decreased the number of total bacteria and Escherichia coli in the cecum of broilers. Microcin C7 also significantly increased short-chain fatty acid (SCFA) and lactic acid levels in the ileum and cecum of broilers. In conclusion, diet supplemented with Microcin C7 significantly improved growth performance, strengthened immune functions, enhanced intestinal barrier, and regulated cecal microbiota of broilers. Therefore, the antimicrobial peptide Microcin C7 may have the potential to be an ideal alternative to antibiotic.

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 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 Distinct Physiologic and Inflammatory Responses Elicited in Baboons after Challenge with Shiga Toxin Type 1 or 2 from Enterohemorrhagic Escherichia coli

2010 ◽  
Vol 78 (6) ◽  
pp. 2497-2504 ◽  
Author(s):  
D. J. Stearns-Kurosawa ◽  
Valta Collins ◽  
Scott Freeman ◽  
Vernon L. Tesh ◽  
Shinichiro Kurosawa
Keyword(s):  
Escherichia Coli ◽  
Nonhuman Primate ◽  
Shiga Toxin ◽  
Inflammatory Responses ◽  
The United States ◽  
Enterohemorrhagic Escherichia Coli ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α

ABSTRACTShiga toxin-producingEscherichia coliis a principal source of regional outbreaks of bloody diarrhea and hemolytic-uremic syndrome in the United States and worldwide. Primary bacterial virulence factors are Shiga toxin types 1 and 2 (Stx1 and Stx2), and we performed parallel analyses of the pathophysiologies elicited by the toxins in nonhuman primate models to identify shared and unique consequences of the toxemias. After a single intravenous challenge with purified Stx1 or Stx2, baboons (Papio) developed thrombocytopenia, anemia, and acute renal failure with loss of glomerular function, in a dose-dependent manner. Differences in the timing and magnitude of physiologic responses were observed between the toxins. The animals were more sensitive to Stx2, with mortality at lower doses, but Stx2-induced renal injury and mortality were delayed 2 to 3 days compared to those after Stx1 challenge. Multiplex analyses of plasma inflammatory cytokines revealed similarities (macrophage chemoattractant protein 1 [MCP-1] and tumor necrosis factor alpha [TNF-α]) and differences (interleukin-6 [IL-6] and granulocyte colony-stimulating factor [G-CSF]) elicited by the toxins with respect to the mediator induced and timing of the responses. Neither toxin induced detectable levels of plasma TNF-α. To our knowledge, this is the first time that thein vivoconsequences of the toxins have been compared in a parallel and reproducible manner in nonhuman primates, and the data show similarities to patient observations. The availability of experimental nonhuman primate models for Stx toxemias provides a reproducible platform for testing antitoxin compounds and immunotherapeutics with outcome criteria that have clinical meaning.

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