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.

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.

scholarly journals Phages as a Cohesive Prophylactic and Therapeutic Approach in Aquaculture Systems

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 564 ◽  
Author(s):  
Maciej Żaczek ◽  
Beata Weber-Dąbrowska ◽  
Andrzej Górski
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Human Life ◽  
Natural Habitat ◽  
Aquatic Organisms ◽  
Economic Losses ◽  
Complex Approach ◽  
Promising Solution ◽  
Phage Treatment

Facing antibiotic resistance has provoked a continuously growing focus on phage therapy. Although the greatest emphasis has always been placed on phage treatment in humans, behind phage application lies a complex approach that can be usefully adopted by the food industry, from hatcheries and croplands to ready-to-eat products. Such diverse businesses require an efficient method for combating highly pathogenic bacteria since antibiotic resistance concerns every aspect of human life. Despite the vast abundance of phages on Earth, the aquatic environment has been considered their most natural habitat. Water favors multidirectional Brownian motion and increases the possibility of contact between phage particles and their bacterial hosts. As the global production of aquatic organisms has rapidly grown over the past decades, phage treatment of bacterial infections seems to be an obvious and promising solution in this market sector. Pathogenic bacteria, such as Aeromonas and Vibrio, have already proved to be responsible for mass mortalities in aquatic systems, resulting in economic losses. The main objective of this work is to summarize, from a scientific and industry perspective, the recent data regarding phage application in the form of targeted probiotics and therapeutic agents in aquaculture niches.

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.

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.

The Genomics and Cell Biology of Host-Beneficial Intracellular Infections

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
John P. McCutcheon
Keyword(s):  
Host Cell ◽  
Cell Biology ◽  
Bacterial Infections ◽  
Host Cells ◽  
Annual Review ◽  
Intracellular Bacteria ◽  
Publication Date ◽  
Cellular Mechanisms ◽  
Intracellular Infections ◽  
Gain Access

Microbes gain access to eukaryotic cells as food for bacteria-grazing protists, for host protection by microbe-killing immune cells, or for microbial benefit when pathogens enter host cells to replicate. But microbes can also gain access to a host cell and become an important—often required—beneficial partner. The oldest beneficial microbial infections are the ancient eukaryotic organelles now called the mitochondrion and plastid. But numerous other host-beneficial intracellular infections occur throughout eukaryotes. Here I review the genomics and cell biology of these interactions with a focus on intracellular bacteria. The genomes of host-beneficial intracellular bacteria have features that span a previously unfilled gap between pathogens and organelles. Host cell adaptations to allow the intracellular persistence of beneficial bacteria are found along with evidence for the microbial manipulation of host cells, but the cellular mechanisms of beneficial bacterial infections are not well understood. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Modulation of host microtubule dynamics by pathogenic bacteria

2012 ◽  
Vol 3 (6) ◽  
pp. 571-580 ◽  
Author(s):  
Girish K. Radhakrishnan ◽  
Gary A. Splitter
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
Small Gtpases ◽  
Microtubule Dynamics ◽  
Effector Proteins ◽  
Host Cells ◽  
Microbial Pathogens ◽  
Survival Strategies ◽  
Future Research ◽  
Bacterial Effectors

AbstractThe eukaryotic cytoskeleton is a vulnerable target of many microbial pathogens during the course of infection. Rearrangements of host cytoskeleton benefit microbes in various stages of their infection cycle such as invasion, motility, and persistence. Bacterial pathogens deliver a number of effector proteins into host cells for modulating the dynamics of actin and microtubule cytoskeleton. Alteration of the actin cytoskeleton is generally achieved by bacterial effectors that target the small GTPases of the host. Modulation of microtubule dynamics involves direct interaction of effector proteins with the subunits of microtubules or recruiting cellular proteins that affect microtubule dynamics. This review will discuss effector proteins from animal and human bacterial pathogens that either destabilize or stabilize host microtubules to advance the infectious process. A compilation of these research findings will provide an overview of known and unknown strategies used by various bacterial effectors to modulate the host microtubule dynamics. The present review will undoubtedly help direct future research to determine the mechanisms of action of many bacterial effector proteins and contribute to understanding the survival strategies of diverse adherent and invasive bacterial pathogens.

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.

scholarly journals Hsp100 Molecular Chaperone ClpB and Its Role in Virulence of Bacterial Pathogens

2021 ◽  
Vol 22 (10) ◽  
pp. 5319
Author(s):  
Sabina Kędzierska-Mieszkowska ◽  
Michal Zolkiewski
Keyword(s):  
Oxidative Stress ◽  
Molecular Chaperone ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Biological Function ◽  
Bacterial Pathogens ◽  
Cellular Proteins ◽  
Induced Stresses ◽  
Aaa Atpases ◽  
And Oxidative Stress

This review focuses on the molecular chaperone ClpB that belongs to the Hsp100/Clp subfamily of the AAA+ ATPases and its biological function in selected bacterial pathogens, causing a variety of human infectious diseases, including zoonoses. It has been established that ClpB disaggregates and reactivates aggregated cellular proteins. It has been postulated that ClpB’s protein disaggregation activity supports the survival of pathogenic bacteria under host-induced stresses (e.g., high temperature and oxidative stress), which allows them to rapidly adapt to the human host and establish infection. Interestingly, ClpB may also perform other functions in pathogenic bacteria, which are required for their virulence. Since ClpB is not found in human cells, this chaperone emerges as an attractive target for novel antimicrobial therapies in combating bacterial infections.

scholarly journals Glycobiology of syndecan-1 in bacterial infections

2018 ◽  
Vol 46 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Rafael S. Aquino ◽  
Yvonne Hui-Fang Teng ◽  
Pyong Woo Park
Keyword(s):  
Cell Surface ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Innate Immune ◽  
Host Cells ◽  
Innate Defense ◽  
Immune Clearance ◽  
Bacterial Adhesins ◽  
A Cell

Syndecan-1 (Sdc1) is a major cell surface heparan sulfate (HS) proteoglycan of epithelial cells, a cell type targeted by many bacterial pathogens early in their pathogenesis. Loss of Sdc1 in mice is a gain-of-function mutation that significantly decreases the susceptibility to several bacterial infections, suggesting that subversion of Sdc1 is an important virulence strategy. HS glycosaminoglycan (GAG) chains of cell surface Sdc1 promote bacterial pathogenesis by facilitating the attachment of bacteria to host cells. Engagement of cell surface Sdc1 HS chains by bacterial adhesins transmits signal through the highly conserved Sdc1 cytoplasmic domain, which can lead to uptake of intracellular bacterial pathogens. On the other hand, several bacteria that do not require Sdc1 for their attachment and invasion stimulate Sdc1 shedding and exploit the capacity of Sdc1 ectodomain HS GAGs to disarm innate defense mechanisms to evade immune clearance. Recent data suggest that select HS sulfate motifs, and not the overall charge of HS, are important in the inhibition of innate immune mechanisms. Here, we discuss several examples of Sdc1 subversion in bacterial infections.

scholarly journals Mycobacterium tuberculosis Infection Drives Mitochondria-Biased Dysregulation of Host Transfer RNA–Derived Fragments

2020 ◽  
Author(s):  
Monika M Looney ◽  
Yin Lu ◽  
Petros C Karakousis ◽  
Marc K Halushka
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Transfer Rna ◽  
Host Cells ◽  
Analysis Tool ◽  
Mycobacterium Tuberculosis Infection ◽  
Micro Rnas

Abstract Background Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, causes 10 million infections and 1.5 million deaths per year worldwide. The success of Mtb as a human pathogen is directly related to its ability to suppress host responses, which are critical for clearing intracellular pathogens. Emerging evidence suggests that key response pathways may be regulated by a novel class of small noncoding RNA, called transfer RNA (tRNA)–derived fragments (tRFs). tRFs can complex with Argonaute proteins to target and degrade messenger RNA targets, similarly to micro RNAs, but have thus far been overlooked in the context of bacterial infections. Methods We generated a novel miRge2.0-based tRF-analysis tool, tRFcluster, and used it to analyze independently generated and publicly available RNA-sequencing datasets to assess tRF dysregulation in host cells following infection with Mtb and other intracellular bacterial pathogens. Results We found that Mtb and Listeria monocytogenes drive dramatic tRF dysregulation, whereas other bacterial pathogens do not. Interestingly, Mtb infection uniquely increased the expression of mitochondria-derived tRFs rather than genomic-derived tRFs, suggesting an association with mitochondrial damage in Mtb infection. Conclusions tRFs are dysregulated in some, but not all, bacterial infections. Biased dysregulation of mitochondria-derived tRFs in Mtb infection suggests a link between mitochondrial distress and tRF production.

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