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Proceedings. Biological Sciences Feb 2024By definition, all pathogens cause some level of harm to their hosts. If this harm occurs while the pathogen is transmitting, it can negatively affect the pathogen's... (Review)
Review
By definition, all pathogens cause some level of harm to their hosts. If this harm occurs while the pathogen is transmitting, it can negatively affect the pathogen's fitness by shortening the duration over which transmission can occur. However, many of the factors that increase virulence (i.e. harm to host) also promote transmission, driving the pathogen population towards an optimal state of intermediate virulence. A wider spectrum of virulence may be maintained among pathogen populations which are structured into multiple discrete strains though direct resource and immune-mediated competition. These various evolutionary outcomes, and the effects of medical and public health interventions, are best understood within a framework that recognizes the complex relationship between transmission and virulence in the context of the antigenic diversity of the pathogen population.
Topics: Humans; Virulence; Biological Evolution; Host-Pathogen Interactions
PubMed: 38320607
DOI: 10.1098/rspb.2023.2043 -
Molecular Microbiology Aug 2002The pathogenic potential of many Gram-negative bacteria is indicated by the possession of a specialized type III secretion system that is used to deliver virulence... (Review)
Review
The pathogenic potential of many Gram-negative bacteria is indicated by the possession of a specialized type III secretion system that is used to deliver virulence effector proteins directly into the cellular environment of the eukaryotic host. Extracellular assemblies of secreted proteins contrive a physical link between the pathogen and host cytosol and enable the translocated effectors to bypass the bacterial and host membranes in a single step. Subsequent interactions of some effector proteins with host cytoskeletal and signalling proteins result in modulation of the cytoskeletal architecture of the aggressed cell and facilitate entry, survival and dissemination of the pathogen. Although the secreted components of type III secretion systems are diverse, many are predicted to share a common coiled-coil structural feature. Coiled-coils are ubiquitous and highly versatile assembly motifs found in a wide range of structural and regulatory proteins. The prevalence of these domains in secreted virulence effector proteins suggests a fundamental contribution to multiple aspects of their function, and evidence accumulating from functional studies suggests an intrinsic involvement of coiled-coils in subunit assembly, translocation and flexible interactions with multiple bacterial and host proteins. The known functional flexibility that coiled-coil domains confer upon proteins provides insights into some of the pathogenic mechanisms used during interaction with the host.
Topics: Bacteria; Bacterial Proteins; Protein Conformation; Virulence
PubMed: 12180912
DOI: 10.1046/j.1365-2958.2002.03083.x -
Canadian Journal of Microbiology Jul 2018The genus Aspergillus includes fungal species that cause major health issues of significant economic importance. These microorganisms are also the culprit for production... (Review)
Review
The genus Aspergillus includes fungal species that cause major health issues of significant economic importance. These microorganisms are also the culprit for production of carcinogenic aflatoxins in grain storages, contaminating crops, and economically straining the production process. Aspergillus fumigatus is a very important pathogenic species, being responsible for high human morbidity and mortality on a global basis. The prevalence of these infections in immunosuppressed individuals is on the rise, and physicians struggle with the diagnosis of these deadly pathogens. Several virulence determinants facilitate fungal invasion and evasion of the host immune response. Metabolic functions are also important for virulence and drug resistance, since they allow fungi to obtain nutrients for their own survival and growth. Following a positive diagnostic identification, mortality rates remain high due, in part, to emerging resistance to frequently used antifungal drugs. In this review, we discuss the role of the main virulence, drug target, and drug resistance determinants. We conclude with the review of new technologies being developed to treat aspergillosis. In particular, microsphere and nanoparticle delivery systems are discussed in the context of improving drug bioavailability. Aspergillus will likely continue to cause problematic infections in immunocompromised patients, so it is imperative to improve treatment options.
Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Resistance, Fungal; Humans; Immunocompromised Host; Nanoparticles; Virulence; Virulence Factors
PubMed: 29586541
DOI: 10.1139/cjm-2017-0749 -
International Journal of Molecular... Apr 2019Cystic fibrosis (CF) is an autosomal recessive genetic disorder which leads to the secretion of a viscous mucus layer on the respiratory epithelium that facilitates... (Review)
Review
Cystic fibrosis (CF) is an autosomal recessive genetic disorder which leads to the secretion of a viscous mucus layer on the respiratory epithelium that facilitates colonization by various bacterial pathogens. The problem of drug resistance has been reported for all the species able to colonize the lung of CF patients, so alternative treatments are urgently needed. In this context, a valid approach is to investigate new natural and synthetic molecules for their ability to counteract alternative pathways, such as virulence regulating quorum sensing (QS). In this review we describe the pathogens most commonly associated with CF lung infections: , , species of the complex and the emerging pathogens , and non-tuberculous Mycobacteria. For each bacterium, the QS system(s) and the molecules targeting the different components of this pathway are described. The amount of investigations published in the last five years clearly indicate the interest and the expectations on antivirulence therapy as an alternative to classical antibiotics.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cystic Fibrosis; Drug Discovery; Humans; Quorum Sensing; Virulence; Virulence Factors
PubMed: 31013936
DOI: 10.3390/ijms20081838 -
PLoS Pathogens Feb 2015DNA can form several secondary structures besides the classic double helix: one that has received much attention in recent years is the G-quadruplex (G4). This is a... (Review)
Review
DNA can form several secondary structures besides the classic double helix: one that has received much attention in recent years is the G-quadruplex (G4). This is a stable four-stranded structure formed by the stacking of quartets of guanine bases. Recent work has convincingly shown that G4s can form in vivo as well as in vitro and can affect both replication and transcription of DNA. They also play important roles at G-rich telomeres. Now, a spate of exciting reports has begun to reveal roles for G4 structures in virulence processes in several important microbial pathogens of humans. Interestingly, these come from a range of kingdoms--bacteria and protozoa as well as viruses--and all facilitate immune evasion in different ways. In particular, roles for G4s have been posited in the antigenic variation systems of bacteria and protozoa, as well as in the silencing of at least two major human viruses, human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV). Although antigenic variation and the silencing of latent viruses are quite distinct from one another, both are routes to immune evasion and the maintenance of chronic infections. Thus, highly disparate pathogens can use G4 motifs to control DNA/RNA dynamics in ways that are relevant to common virulence phenotypes. This review explores the evidence for G4 biology in such processes across a range of important human pathogens.
Topics: Bacteria; G-Quadruplexes; Humans; Virulence; Viruses
PubMed: 25654363
DOI: 10.1371/journal.ppat.1004562 -
Microbiology and Molecular Biology... Dec 2013Clostridium difficile is a Gram-positive, spore-forming organism which infects and colonizes the large intestine, produces potent toxins, triggers inflammation, and... (Review)
Review
Clostridium difficile is a Gram-positive, spore-forming organism which infects and colonizes the large intestine, produces potent toxins, triggers inflammation, and causes significant systemic complications. Treating C. difficile infection (CDI) has always been difficult, because the disease is both caused and resolved by antibiotic treatment. For three and a half decades, C. difficile has presented a treatment challenge to clinicians, and the situation took a turn for the worse about 10 years ago. An increase in epidemic outbreaks related to CDI was first noticed around 2003, and these outbreaks correlated with a sudden increase in the mortality rate of this illness. Further studies discovered that these changes in CDI epidemiology were associated with the rapid emergence of hypervirulent strains of C. difficile, now collectively referred to as NAP1/BI/027 strains. The discovery of new epidemic strains of C. difficile has provided a unique opportunity for retrospective and prospective studies that have sought to understand how these strains have essentially replaced more historical strains as a major cause of CDI. Moreover, detailed studies on the pathogenesis of NAP1/BI/027 strains are leading to new hypotheses on how this emerging strain causes severe disease and is more commonly associated with epidemics. In this review, we provide an overview of CDI, discuss critical mechanisms of C. difficile virulence, and explain how differences in virulence-associated factors between historical and newly emerging strains might explain the hypervirulence exhibited by this pathogen during the past decade.
Topics: Animals; Bacterial Proteins; Clostridioides difficile; Humans; Virulence; Virulence Factors
PubMed: 24296572
DOI: 10.1128/MMBR.00017-13 -
Journal of Bacteriology Nov 2012The increasing interest in the human microbiota raises some interesting questions about the terminology we use to describe some of the structures and strategies employed... (Review)
Review
The increasing interest in the human microbiota raises some interesting questions about the terminology we use to describe some of the structures and strategies employed by commensal and pathogenic microbes to compete in these complex biological ecosystems. For example, all microbes arriving in the alimentary tract face the task of surviving passage through the stomach, coping with bile, interacting with the immune system, competing with the established microbiota, and obtaining sufficient nutrients to gain a foothold in this hostile environment. It is not surprising then that many gastrointestinal microbes (both pathogens and commensals) use similar strategies to overcome the challenges associated with this particular biological niche. Given that many of these structures and strategies were discovered and characterized in pathogens and because they often play important roles in establishing and maintaining an infection, they have often been characterized as virulence factors. It would be misleading to describe the same strategies and structures found in harmless commensals as "virulence factors," since they represent a sine qua non for life in the gastrointestinal tract. It may be time to reconsider and refer to them as "niche factors," both in terms of providing scientific accuracy but also in light of the growing interest in using gut microbes as probiotics, where the distinction between virulence factors and niche factors is likely to be very important from a regulatory perspective.
Topics: Bacteria; Bacterial Physiological Phenomena; Gastrointestinal Tract; Humans; Terminology as Topic; Virulence; Virulence Factors
PubMed: 22821969
DOI: 10.1128/JB.00980-12 -
Microbiology and Molecular Biology... Mar 2012Cell-to-cell communication is a major process that allows bacteria to sense and coordinately react to the fluctuating conditions of the surrounding environment. In... (Review)
Review
Cell-to-cell communication is a major process that allows bacteria to sense and coordinately react to the fluctuating conditions of the surrounding environment. In several pathogens, this process triggers the production of virulence factors and/or a switch in bacterial lifestyle that is a major determining factor in the outcome and severity of the infection. Understanding how bacteria control these signaling systems is crucial to the development of novel antimicrobial agents capable of reducing virulence while allowing the immune system of the host to clear bacterial infection, an approach likely to reduce the selective pressures for development of resistance. We provide here an up-to-date overview of the molecular basis and physiological implications of cell-to-cell signaling systems in Gram-negative bacteria, focusing on the well-studied bacterium Pseudomonas aeruginosa. All of the known cell-to-cell signaling systems in this bacterium are described, from the most-studied systems, i.e., N-acyl homoserine lactones (AHLs), the 4-quinolones, the global activator of antibiotic and cyanide synthesis (GAC), the cyclic di-GMP (c-di-GMP) and cyclic AMP (cAMP) systems, and the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), to less-well-studied signaling molecules, including diketopiperazines, fatty acids (diffusible signal factor [DSF]-like factors), pyoverdine, and pyocyanin. This overview clearly illustrates that bacterial communication is far more complex than initially thought and delivers a clear distinction between signals that are quorum sensing dependent and those relying on alternative factors for their production.
Topics: Animals; Cell Communication; Humans; Pseudomonas aeruginosa; Signal Transduction; Virulence
PubMed: 22390972
DOI: 10.1128/MMBR.05007-11 -
Current Opinion in Plant Biology Aug 2017Small RNA (sRNA) induces RNA interference (RNAi) in almost all eukaryotes. While sRNAs can move within an organism, they can also move between interacting organisms... (Review)
Review
Small RNA (sRNA) induces RNA interference (RNAi) in almost all eukaryotes. While sRNAs can move within an organism, they can also move between interacting organisms to induce gene silencing, a phenomenon called 'cross-kingdom RNAi'. Some sRNAs from pathogens or pests move into host cells and suppress host immunity in both plants and animals; whereas some host sRNAs travel into pathogen/pest cells to inhibit their virulence. Moreover, uptake of exogenous RNAs from the environment was recently discovered in certain fungal pathogens, which makes it possible to suppress fungal diseases by directly applying pathogen-targeting RNAs on crops and post-harvest products. This new-generation of RNA-based fungicides is powerful, environmentally friendly, and can be easily adapted to control multiple diseases simultaneously.
Topics: Host-Pathogen Interactions; Plant Immunity; RNA, Plant; RNA, Small Interfering; Virulence
PubMed: 28570950
DOI: 10.1016/j.pbi.2017.05.003 -
Nihon Saikingaku Zasshi. Japanese... 2014Most of our current knowledge about the gene regulation of pathogen comes from studies with in vitro conditions that mimic their host environments, revealing many types... (Review)
Review
Most of our current knowledge about the gene regulation of pathogen comes from studies with in vitro conditions that mimic their host environments, revealing many types of virulence genes and their regulatory network. Recent advances in DNA sequencing and techniques for transcriptome analysis allow us to identify pathogenic genes specifically expressed in vivo. Analyses for gene expression of pathogens in response to the host environment, including immune response and change of bacterial flora during infection, provide clues to understanding the underlying events to establish the infectious diseases. Here, we would like to introduce next epoch-making ideas and concepts to understand the real picture of microbial infection through the recent works of gene regulation in host environments.
Topics: Animals; Autophagy; Bacteria; Bacterial Infections; Evolution, Molecular; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; Host-Pathogen Interactions; Humans; Organelles; RNA Processing, Post-Transcriptional; RNA, Small Cytoplasmic; Sequence Analysis, DNA; Symbiosis; Virulence
PubMed: 25186644
DOI: 10.3412/jsb.69.539