scholarly journals The Wnt/β-Catenin Signaling Pathway Controls the Inflammatory Response in Infections Caused by Pathogenic Bacteria

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Octavio Silva-García ◽  
Juan J. Valdez-Alarcón ◽  
Víctor M. Baizabal-Aguirre
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Tissue Injury ◽  
Adaptive Immune Response ◽  
Host Cells ◽  
Wide Range ◽  
The Many ◽  
Canonical Wnt

Innate immunity against pathogenic bacteria is critical to protect host cells from invasion and infection as well as to develop an appropriate adaptive immune response. During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation. The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury. Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections. Our main goal in this review is to discuss the mechanism used by several pathogenic bacteria to modulate the inflammatory response through the Wnt/β-catenin signaling pathway. We think that a deep insight into the role of Wnt/β-catenin signaling in the inflammation may open new venues for biotechnological approaches designed to control bacterial infectious diseases.

Potential role of a series of lysine-/leucine-rich antimicrobial peptide in inhibiting lipopolysaccharide-induced inflammation

2018 ◽  
Vol 475 (22) ◽  
pp. 3687-3706 ◽  
Author(s):  
Weibing Dong ◽  
Xin Zhu ◽  
Xuan Zhou ◽  
Ying Yang ◽  
Xin Yan ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Antimicrobial Activities ◽  
Host Cells ◽  
Inflammatory Factors ◽  
Human Macrophage ◽  
U937 Cells ◽  
Wide Range ◽  
Anti Inflammatory

Antimicrobial peptides have broad-spectrum killing activities against bacteria, enveloped viruses, fungi and several parasites via cell membrane permeation and exhibit primarily immunomodulatory and anti-infective functions in their interactions with host cells. However, the mechanism underlying their anti-inflammatory activity remains to be elucidated. L-K6, an analog of temporin-1CEb isolated from the skin secretion of Rana chensinensis, has demonstrated a wide range of antimicrobial activities against gram-negative and gram-positive bacteria. In this study, the potent anti-inflammatory mechanism of L-K6 and its analogs in lipopolysaccharide (LPS)-stimulated human macrophage U937 cells were evaluated. We found that L-K6 suppressed the expression of inflammatory factors by two downstream signaling components in the MyD88-dependent pathway, including the mitogen-activated protein kinases (MAPKs) and the NF (nuclear factor)-κB signaling pathway, but its analog L-K5, which had the same amino acid sequence as L-K6 but no Lys residue at the –COOH terminal, only inhibited the phosphorylation of I-κB and NF-κB. Importantly, L-K6 and L-K5 were actively taken up by U937 cells through an independent cell membrane disruption mechanism and were eventually localized to the perinuclear region. The L-K6 uptake process was mediated by endocytosis, but L-K5 was specifically taken up by U937 cells via TLR4 endocytosis. Our results demonstrated that L-K6 can neutralize LPS and diassociate LPS micelles to inhibit LPS from triggering the proinflammatory signaling pathway, and by partially inhibiting inflammatory responses by the intracellular target. However, L-K5 may mainly inhibit proinflammatory responses by intracellular reporters to modulate the NF-κB signaling pathway.

scholarly journals Chemical Inhibitors of the Type Three Secretion System: Disarming Bacterial Pathogens

2012 ◽  
Vol 56 (11) ◽  
pp. 5433-5441 ◽  
Author(s):  
Miles C. Duncan ◽  
Roger G. Linington ◽  
Victoria Auerbuch
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
Secretion System ◽  
Effector Proteins ◽  
Host Cells ◽  
Magic Bullet ◽  
Antimicrobial Drugs ◽  
Type Three Secretion System ◽  
Type Three Secretion

ABSTRACTThe recent and dramatic rise of antibiotic resistance among bacterial pathogens underlies the fear that standard treatments for infectious disease will soon be largely ineffective. Resistance has evolved against nearly every clinically used antibiotic, and in the near future, we may be hard-pressed to treat bacterial infections previously conquered by “magic bullet” drugs. While traditional antibiotics kill or slow bacterial growth, an important emerging strategy to combat pathogens seeks to block the ability of bacteria to harm the host by inhibiting bacterial virulence factors. One such virulence factor, the type three secretion system (T3SS), is found in over two dozen Gram-negative pathogens and functions by injecting effector proteins directly into the cytosol of host cells. Without T3SSs, many pathogenic bacteria are unable to cause disease, making the T3SS an attractive target for novel antimicrobial drugs. Interdisciplinary efforts between chemists and microbiologists have yielded several T3SS inhibitors, including the relatively well-studied salicylidene acylhydrazides. This review highlights the discovery and characterization of T3SS inhibitors in the primary literature over the past 10 years and discusses the future of these drugs as both research tools and a new class of therapeutic agents.

INTRODUCTION

1988 ◽  
Vol 34 (3) ◽  
pp. 280-280
Author(s):  
Gregor Reid ◽  
Andrew W. Bruce
Keyword(s):  
Medical Education ◽  
American Medical ◽  
Continuing Medical Education ◽  
Bacterial Infections ◽  
University Of Toronto ◽  
Future Developments ◽  
Wide Range ◽  
Microbial Infections ◽  
The Many ◽  
The University

The Lister Symposium was held primarily to review the latest concepts of the mechanisms of bacterial infections, and to highlight the research being carried out currently in Toronto and in Canada. The inclusion of several speakers from outside of Toronto added a strong foundation for the meeting.A wide range of topics were addressed and these demonstrated the many areas of research being pursued to better understand the pathogenesis of microbial infections. By drawing together physicians, scientists, and students from a variety of disciplines, it was hoped that the Lister Symposium would contribute, not only to our knowledge of medicine and science in this field, but also to the continued local and national cooperation required for first-class investigative research.This meeting was the first of its kind held under the auspices of the Department of Surgery at the University of Toronto, demonstrating its commitment to research and interdepartmental collaboration. We are most grateful to Professor Bernard Langer, Chairman of the Department of Surgery, for his support in this regard. The assistance of our sponsors and the Continuing Medical Education Office facilitated a wide outreach and enabled recognition of the course and accreditation for Canadian and American Medical participants. It is hoped that this material will provide a useful reference for future developments in the field.

scholarly journals MicroRNA-30e-5p Regulates SOCS1 and SOCS3 During Bacterial Infection

2021 ◽  
Vol 10 ◽  
Author(s):  
Richa Mishra ◽  
Pandikannan Krishnamoorthy ◽  
Himanshu Kumar
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Bacterial Infection ◽  
Messenger Rna ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Innate Immune ◽  
Host Cells ◽  
Microbial Infection ◽  
Major Player

Host innate immunity is the major player against continuous microbial infection. Various pathogenic bacteria adopt the strategies to evade the immunity and show resistance toward the various established therapies. Despite the advent of many antibiotics for bacterial infections, there is a substantial need for the host-directed therapies (HDTs) to combat the infection. HDTs are recently being adopted to be useful in eradicating intracellular bacterial infection. Changing the innate immune responses of the host cells alters pathogen’s ability to reside inside the cell. MicroRNAs are the small non-coding endogenous molecules and post-transcriptional regulators to target the 3’UTR of the messenger RNA. They are reported to modulate the host’s immune responses during bacterial infections. Exploiting microRNAs as a therapeutic candidate in HDTs upon bacterial infection is still in its infancy. Here, initially, we re-analyzed the publicly available transcriptomic dataset of macrophages, infected with different pathogenic bacteria and identified significant genes and microRNAs common to the differential infections. We thus identified and miR-30e-5p, to be upregulated in different bacterial infections which enhances innate immunity to combat bacterial replication by targeting key negative regulators such as SOCS1 and SOCS3 of innate immune signaling pathways. Therefore, we propose miR-30e-5p as one of the potential candidates to be considered for additional clinical validation toward HDTs.

EP3: an ensemble predictor that accurately identifies type III secreted effectors

2020 ◽  
Author(s):  
Jing Li ◽  
Leyi Wei ◽  
Fei Guo ◽  
Quan Zou
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Predictive Ability ◽  
Host Cells ◽  
Secretion Systems ◽  
Accurate Identification ◽  
Type Iii ◽  
Unknown Protein ◽  
Type Iii Secretion Systems ◽  
Pathogenic Escherichia Coli

Abstract Type III secretion systems (T3SS) can be found in many pathogenic bacteria, such as Dysentery bacillus, Salmonella typhimurium, Vibrio cholera and pathogenic Escherichia coli. The routes of infection of these bacteria include the T3SS transferring a large number of type III secreted effectors (T3SE) into host cells, thereby blocking or adjusting the communication channels of the host cells. Therefore, the accurate identification of T3SEs is the precondition for the further study of pathogenic bacteria. In this article, a new T3SEs ensemble predictor was developed, which can accurately distinguish T3SEs from any unknown protein. In the course of the experiment, methods and models are strictly trained and tested. Compared with other methods, EP3 demonstrates better performance, including the absence of overfitting, strong robustness and powerful predictive ability. EP3 (an ensemble predictor that accurately identifies T3SEs) is designed to simplify the user’s (especially nonprofessional users) access to T3SEs for further investigation, which will have a significant impact on understanding the progression of pathogenic bacterial infections. Based on the integrated model that we proposed, a web server had been established to distinguish T3SEs from non-T3SEs, where have EP3_1 and EP3_2. The users can choose the model according to the species of the samples to be tested. Our related tools and data can be accessed through the link http://lab.malab.cn/∼lijing/EP3.html.

Regulation of Immune Responses during Acute GvHD Via the IL-33/ST2 Axis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 844-844
Author(s):  
Dawn K Reichenbach ◽  
Vincent Schwarze ◽  
Benjamin M Matta ◽  
Victor Tkachev ◽  
Elizabeth Lieberknecht ◽  
...  
Keyword(s):  
T Cells ◽  
Inflammatory Response ◽  
Acute Gvhd ◽  
Tissue Injury ◽  
Suppressor Cells ◽  
Host Cells ◽  
Soluble Form ◽  
Signaling Mechanism ◽  
Donor T Cells ◽  
Host Signaling

Abstract The IL-1 superfamily member IL-33 is produced in barrier tissues. IL-33 binds to the receptor suppression of tumorigenicity 2 (ST2), expressed on stromal cells, regulatory T cells (Tregs), myeloid derived suppressor cells (MDSCs), and macrophages. IL-33 has both anti-inflammatory and pro-inflammatory properties. It is not known if IL-33 plays a role in acute GvHD, and if so what properties it exerts. By immunohistochemistry staining of gut tissues, IL-33 production by non-hematopoietic cells was increased in mice post-conditioning and in patients during GvHD. To determine whether IL-33 could augment GvHD via a host signaling mechanism, we compared st2-/-to wildtype (wt) hosts and observed decreased GvHD lethality (Figure 1A). Additionally, IL-33-/- versus wt hosts had a marked decrease in GvHD lethality and reduced TNFα production. Conversely, IL-33 administration during the peak inflammatory response worsened GvHD. Previous studies have shown increased levels of the soluble form of ST2 (sST2) are a biomarker for steroid-refractory GvHD (Vander Lugt, NEJM, 2013). We hypothesized that sST2 acted not only as an indicator of tissue injury and biomarker of GvHD but also as an immune modulator during GvHD. In rodents, we found that ST2 was upregulated on alloreactive T cells and sST2 increased as GvHD progressed. St2-/-versus wt donor T cells had a marked reduction in GvHD lethality (Figure 1B) without compromise of graft-vs-leukemia responses. Comparable data was seen in 2 different strain combinations. Alloantigen-induced IL-18 receptor upregulation was significantly lower in the absence of ST2, which was linked to significantly reduced IFNγ production by st2-/- vs wt CD4 and CD8 T cells during GvHD. Similarly, sST2 transgenic hosts and wt recipients given exogenous sST2-Fc fusion protein infusions (Figure 1C) to block ST2/IL-33 interaction each had significantly reduced GVHD lethality, establishing the functional role of ST2 as a decoy receptor modulating GVHD. During the peak of the GvHD inflammatory response, IL-33 signalling of either donor or host cells promoted activation of donor T cells, while the use of exogenous sST2-Fc protein to prevent IL33/ST2 engagement ameliorates disease. Together, these studies point to targeting of the IL-33/ST2 axis as a novel and potent target for GvHD therapy. Disclosures Warncke: Novartis Pharma AG: Employment. Junt:Novartis Pharma AG: Employment.

scholarly journals Beyond homeostasis: potassium and pathogenesis during bacterial infections

2021 ◽  
Author(s):  
Elyza A. Do ◽  
Casey M. Gries
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Virulence Gene ◽  
Potassium Transport ◽  
Host Cells ◽  
Mineral Nutrient ◽  
Inflammasome Activation ◽  
Bacterial Cells ◽  
Virulence Gene Expression ◽  
Neuronal Transmission

Potassium is an essential mineral nutrient required by all living cells for normal physiological function. Maintaining intracellular potassium homeostasis during bacterial infection is therefore a requirement for the survival of both host and pathogen. However, pathogenic bacteria require potassium transport not only to fulfill nutritional and chemiosmotic requirements, but potassium has been shown to directly modulate virulence gene expression, antimicrobial resistance, and biofilm formation. Host cells also require potassium to maintain fundamental biological processes as such as renal function, muscle contraction, and neuronal transmission, however, potassium flux also contributes to critical immunological and antimicrobial processes such as cytokine production and inflammasome activation. Here we review the role and regulation of potassium transport and signaling during infection in both mammalian and bacterial cells and highlight the importance of potassium to the success and survival of each organism.

scholarly journals An Investigation of Potential Health Risks from Zoonotic Bacterial Pathogens Associated with Farm Rats

2020 ◽  
Vol 14 ◽  
pp. 117863022094224
Author(s):  
Lorina Badger-Emeka ◽  
Yasmeen Al-Mulhim ◽  
Fatimah Al-Muyidi ◽  
Maram Busuhail ◽  
Salma Alkhalifah ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Rattus Rattus ◽  
Bacterial Pathogen ◽  
Automated System ◽  
Potential Health ◽  
Zoonotic Infections ◽  
Wide Range ◽  
Significant Difference

Background: The 21st century has seen a wide range of diseases resulting from zoonotic infections, of which bacterial infections have led to outbreaks of food-borne diseases. Aim: The study looks at bacterial pathogen carriage by farm rats and their antimicrobial susceptibility, with the view of providing insights for antimicrobial surveillance. Method: Farm rats of Rattus rattus species where randomly collected alive from farms in Al-Ahsa using food baits. They were anaesthetize with urethane within 4 h of collection and were unconscious for the collection of samples. Basic bacteriological culturing methods were used for culturing of bacterial isolates on selective media while the Vitek 2 compact automated system (BioMerieux, Marcy L’Etoile, France) was used for bacteria identification and antimicrobial susceptibility test. Obtained data were analysed using chi-square and paired t-test with significant difference between sensitive and resistance to antimicrobial susceptibility taken at P < .05. Results: Isolated Gramme-negative pathogenic bacteria included strains of Escherichia coli, Pseudomonas oryzihabitans, strains of Pseudomonas aeruginosa, and Salmonella. For the Gramme-positive bacteria, 4 strains of Staphylococcus aureus were encountered. Other Gramme-positive bacteria were coagulase-negative Staphylococcal species (CoNS) as well as Staphylococcus lugdunensis. There was a 100% resistance to the penicillins and a high resistance to imipenem (71%) by the Staphylococcal isolates. Resistance was also high against the β-lactams by the Gramme-positive bacteria isolates. For the Gramme-negative bacteria, there was a higher than 50% resistance by the isolates against the following antibiotics: ampicillin (78%), amoxicillin/clavulanic acid (67%), cefotaxime (77%), ceftazidime (67%), cefepime (78%), norfloxacin (67%), nitrofurantoin (67%), and trimethoprim/sulfamethoxazole (78%). Conclusion: The results showed high antimicrobial resistance that will need monitoring for control of spread from farm rats to humans.

scholarly journals Pathogenicity Islands in Bacterial Pathogenesis

2004 ◽  
Vol 17 (1) ◽  
pp. 14-56 ◽  
Author(s):  
Herbert Schmidt ◽  
Michael Hensel
Keyword(s):  
Cell Biology ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Human Life ◽  
Bacterial Pathogens ◽  
Genomic Islands ◽  
Model Systems ◽  
Host Cells ◽  
Pathogenicity Islands ◽  
Molecular Features

SUMMARY In this review, we focus on a group of mobile genetic elements designated pathogenicity islands (PAI). These elements play a pivotal role in the virulence of bacterial pathogens of humans and are also essential for virulence in pathogens of animals and plants. Characteristic molecular features of PAI of important human pathogens and their role in pathogenesis are described. The availability of a large number of genome sequences of pathogenic bacteria and their benign relatives currently offers a unique opportunity for the identification of novel pathogen-specific genomic islands. However, this knowledge has to be complemented by improved model systems for the analysis of virulence functions of bacterial pathogens. PAI apparently have been acquired during the speciation of pathogens from their nonpathogenic or environmental ancestors. The acquisition of PAI not only is an ancient evolutionary event that led to the appearance of bacterial pathogens on a timescale of millions of years but also may represent a mechanism that contributes to the appearance of new pathogens within a human life span. The acquisition of knowledge about PAI, their structure, their mobility, and the pathogenicity factors they encode not only is helpful in gaining a better understanding of bacterial evolution and interactions of pathogens with eukaryotic host cells but also may have important practical implications such as providing delivery systems for vaccination, tools for cell biology, and tools for the development of new strategies for therapy of bacterial infections.

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