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 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.

Dealing with oxidative stress and iron starvation in microorganisms: an overviewThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 264-272 ◽  
Author(s):  
Julie-Anna M. Benjamin ◽  
Guillaume Desnoyers ◽  
Audrey Morissette ◽  
Hubert Salvail ◽  
Eric Massé
Keyword(s):  
Oxidative Stress ◽  
Cellular Response ◽  
Pathogenic Bacteria ◽  
Iron Starvation ◽  
Intracellular Iron ◽  
Iron Sulfur Clusters ◽  
Successful Infection ◽  
Health And Disease ◽  
And Oxidative Stress ◽  
Selection Of

Iron starvation and oxidative stress are 2 hurdles that bacteria must overcome to establish an infection. Pathogenic bacteria have developed many strategies to efficiently infect a broad range of hosts, including humans. The best characterized systems make use of regulatory proteins to sense the environment and adapt accordingly. For example, iron–sulfur clusters are critical for sensing the level and redox state of intracellular iron. The regulatory small RNA (sRNA) RyhB has recently been shown to play a central role in adaptation to iron starvation, while the sRNA OxyS coordinates cellular response to oxidative stress. These regulatory sRNAs are well conserved in many bacteria and have been shown to be essential for establishing a successful infection. An overview of the different strategies used by bacteria to cope with iron starvation and oxidative stress is presented here.

scholarly journals AlgU Controls Expression of Virulence Genes in Pseudomonas syringae pv. tomato DC3000

2016 ◽  
Vol 198 (17) ◽  
pp. 2330-2344 ◽  
Author(s):  
Eric Markel ◽  
Paul Stodghill ◽  
Zhongmeng Bao ◽  
Christopher R. Myers ◽  
Bryan Swingle
Keyword(s):  
Oxidative Stress ◽  
Pseudomonas Syringae ◽  
Stress Responses ◽  
Sigma Factor ◽  
Pathogenic Bacteria ◽  
Promoter Sequence ◽  
Tomato Dc3000 ◽  
Content Type ◽  
Plant Pathogenic Bacteria ◽  
And Oxidative Stress

ABSTRACTPlant-pathogenic bacteria are able to integrate information about their environment and adjust gene expression to provide adaptive functions. AlgU, an extracytoplasmic function (ECF) sigma factor encoded byPseudomonas syringae, controls expression of genes for alginate biosynthesis and genes involved with resisting osmotic and oxidative stress. AlgU is active while these bacteria are associated with plants, where its presence supports bacterial growth and disease symptoms. We found that AlgU is an important virulence factor forP. syringaepv. tomato DC3000 but that alginate production is dispensable for disease in host plants. This implies that AlgU regulates additional genes that facilitate bacterial pathogenesis. We used transcriptome sequencing (RNA-seq) to characterize the AlgU regulon and chromatin immunoprecipitation sequencing (ChIP-seq) to identify AlgU-regulated promoters associated with genes directly controlled by this sigma factor. We found that in addition to genes involved with alginate and osmotic and oxidative stress responses, AlgU regulates genes with known virulence functions, including components of the Hrp type III secretion system, virulence effectors, and thehrpLandhrpRStranscription regulators. These data suggest thatP. syringaepv. tomato DC3000 has adapted to use signals that activate AlgU to induce expression of important virulence functions that facilitate survival and disease in plants.IMPORTANCEPlant immune systems produce antimicrobial and bacteriostatic conditions in response to bacterial infection. Plant-pathogenic bacteria are adapted to suppress and/or tolerate these conditions; however, the mechanisms controlling these bacterial systems are largely uncharacterized. The work presented here provides a mechanistic explanation for howP. syringaepv. tomato DC3000 coordinates expression of multiple genetic systems, including those dedicated to pathogenicity, in response to environmental conditions. This work demonstrates the scope of AlgU regulation inP. syringaepv. tomato DC3000 and characterizes the promoter sequence regulated by AlgU in these bacteria.

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 Using the Wax moth larvaGalleria mellonellainfection model to detect emerging bacterial pathogens

2018 ◽  
Author(s):  
Rafael J. Hernandez ◽  
Elze Hesse ◽  
Andrea J. Dowling ◽  
Nicola M. Coyle ◽  
Edward J. Feil ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Genomic Island ◽  
Galleria Mellonella ◽  
Bacterial Pathogens ◽  
Innate Immune ◽  
Coastal Environments ◽  
Novel Method ◽  
Highly Virulent ◽  
Wax Moth

AbstractClimate change, changing farming practices, social and demographic changes and rising levels of antibiotic resistance are likely to lead to future increases in opportunistic bacterial infections that are more difficult to treat. Uncovering the prevalence and identity of pathogenic bacteria in the environment is key to assessing transmission risks. We describe the first use of the Wax moth larvaGalleria mellonella, a well-established model for the mammalian innate immune system, to selectively enrich and characterize pathogens from coastal environments in the South West of the U.K. Whole-genome sequencing of highly virulent isolates revealed amongst others aProteus mirabilisstrain carrying theSalmonellaSGI1 genomic island not reported from the U.K. before and the recently described speciesVibrio injenensishitherto only reported from human patients in Korea. Our novel method has the power to detect novel bacterial pathogens in the environment that potentially pose a serious risk to public health.

scholarly journals Exploring the Modulation of Immune Response and Oxidative Stress of Intracellular Pathogens Using Nanoparticles Encapsulating Drugs

2020 ◽  
Author(s):  
Ramendra Pati Pandey ◽  
Anjali Priyadarshini ◽  
Archana Gupta ◽  
Arpana Vibhuti ◽  
Elcio Leal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Delivery ◽  
Immune Response ◽  
Immune System ◽  
Bacterial Infections ◽  
Reactive Nitrogen ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Antioxidant Defences ◽  
And Oxidative Stress

The immune system is a dynamic network of cells and cytokines are the major mediators of immune responses which combat pathogens. Based on the cytokine production, effector T cells differentiate into subsets known as Th1, Th2, Th17 or Treg (T regulatory). This system serves as a barrier to intracellular pathogens, bacterial infections and stimulates the production of reactive oxygen species (ROS), reactive nitrogen intermediates (RNI) and nitric oxide (NO), which diffuses across membranes and engulfs intracellular pathogens. Oxidative stress occurs when ROS, reactive nitrogen species (RNS) production and antioxidant defences become imbalanced. Oxidative stress generated by infected cells produces a substantial amount of free radicals which enables killing of intracellular pathogens. Intracellular pathogens are exposed to endogenous ROS as part of normal aerobic respiration, also aexogenous ROS and RNS are generated by the host immune system in response to infection. Nanoparticles which are designed for drug delivery are capable of trapping the desired drug in the particles which protects the drug from enzymatic degradation in a biological system. The small (subcellular) size of nanoparticles enables higher intracellular uptake of the drug which results in the reduction of the concentration of free drugs reducing their toxic effect. Research on the modulation of immune response and oxidative stress using nanoparticles used to encapsulate drugs has yet to be explored fully. In this review we illustrate the immune activation and generation of oxidative stress properties which are mediated by nanoparticle encapsulated drug delivery systems which can make the therapy more effective in case of diseases caused by intracellular pathogens.

scholarly journals Polyphosphate Kinase 2 (PPK2) Enzymes: Structure, Function, and Roles in Bacterial Physiology and Virulence

2022 ◽  
Vol 23 (2) ◽  
pp. 670
Author(s):  
Nolan Neville ◽  
Nathan Roberge ◽  
Zongchao Jia
Keyword(s):  
Molecular Chaperone ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Virulence ◽  
Polyphosphate Kinase ◽  
Biological Functions ◽  
Inorganic Polyphosphate ◽  
Bacterial Physiology ◽  
Enzyme Families ◽  
Phosphorus Storage

Inorganic polyphosphate (polyP) has been implicated in an astonishing array of biological functions, ranging from phosphorus storage to molecular chaperone activity to bacterial virulence. In bacteria, polyP is synthesized by polyphosphate kinase (PPK) enzymes, which are broadly subdivided into two families: PPK1 and PPK2. While both enzyme families are capable of catalyzing polyP synthesis, PPK1s preferentially synthesize polyP from nucleoside triphosphates, and PPK2s preferentially consume polyP to phosphorylate nucleoside mono- or diphosphates. Importantly, many pathogenic bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii encode at least one of each PPK1 and PPK2, suggesting these enzymes may be attractive targets for antibacterial drugs. Although the majority of bacterial polyP studies to date have focused on PPK1s, PPK2 enzymes have also begun to emerge as important regulators of bacterial physiology and downstream virulence. In this review, we specifically examine the contributions of PPK2s to bacterial polyP homeostasis. Beginning with a survey of the structures and functions of biochemically characterized PPK2s, we summarize the roles of PPK2s in the bacterial cell, with a particular emphasis on virulence phenotypes. Furthermore, we outline recent progress on developing drugs that inhibit PPK2 enzymes and discuss this strategy as a novel means of combatting bacterial infections.

scholarly journals Using the wax moth larvaGalleria mellonellainfection model to detect emerging bacterial pathogens

PeerJ ◽  
2019 ◽  
Vol 6 ◽  
pp. e6150 ◽  
Author(s):  
Rafael J. Hernandez ◽  
Elze Hesse ◽  
Andrea J. Dowling ◽  
Nicola M. Coyle ◽  
Edward J. Feil ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Galleria Mellonella ◽  
Bacterial Pathogens ◽  
Innate Immune ◽  
Coastal Environments ◽  
Novel Method ◽  
The Uk ◽  
Highly Virulent ◽  
Wax Moth

Climate change, changing farming practices, social and demographic changes and rising levels of antibiotic resistance are likely to lead to future increases in opportunistic bacterial infections that are more difficult to treat. Uncovering the prevalence and identity of pathogenic bacteria in the environment is key to assessing transmission risks. We describe the first use of the Wax moth larvaGalleria mellonella, a well-established model for the mammalian innate immune system, to selectively enrich and characterize pathogens from coastal environments in the South West of the UK. Whole-genome sequencing of highly virulent isolates revealed amongst others aProteus mirabilisstrain carrying theSalmonellaSGI1 genomic island not reported from the UK before and the recently described speciesVibrio injenensishitherto only reported from human patients in Korea. Our novel method has the power to detect bacterial pathogens in the environment that potentially pose a serious risk to public health.

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