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Frontiers in Cellular and Infection... 2017Redundancy has been referred to as a state of no longer being needed or useful. Microbiologists often theorize that the only case of true redundancy in a haploid... (Review)
Review
Redundancy has been referred to as a state of no longer being needed or useful. Microbiologists often theorize that the only case of true redundancy in a haploid organism would be a recent gene duplication event, prior to divergence through selective pressure. However, a growing number of examples exist where an organism encodes two genes that appear to perform the same function. For example, many pathogens translocate multiple effector proteins into hosts. While disruption of individual effector genes does not result in a discernable phenotype, deleting genes in combination impairs pathogenesis: this has been described as redundancy. In many cases, this apparent redundancy could be due to limitations of laboratory models of pathogenesis that do not fully recapitulate the disease process. Alternatively, it is possible that the selective advantage achieved by this perceived redundancy is too subtle to be measured in the laboratory. Moreover, there are numerous possibilities for different types of redundancy. The most common and recognized form of redundancy is functional redundancy whereby two proteins have similar biochemical activities and substrate specificities allowing each one to compensate in the absence of the other. However, redundancy can also exist between seemingly unrelated proteins that manipulate the same or complementary host cell pathways. In this article, we outline 5 types of redundancy in pathogenesis: molecular, target, pathway, cellular process, and system redundancy that incorporate the biochemical activities, the host target specificities and the impact of effector function on the pathways and cellular process they modulate. For each type of redundancy, we provide examples from pathogenesis as this organism employs over 300 secreted virulence proteins and loss of individual proteins rarely impacts intracellular growth. We also discuss selective pressures that drive the maintenance of redundant mechanisms, the current methods used to resolve redundancy and features that distinguish between redundant and non-redundant virulence mechanisms.
Topics: Bacterial Proteins; Gene Duplication; Genes, Bacterial; Host-Pathogen Interactions; Humans; Legionella; Legionella pneumophila; Legionellosis; Mutagenesis, Insertional; Phenotype; Transcription Factors; Virulence
PubMed: 29188194
DOI: 10.3389/fcimb.2017.00467 -
Drug Design, Development and Therapy 2016Pathogens deploy an arsenal of virulence factors (VFs) to establish themselves within their infectious niche. The discovery of antimicrobial compounds and their... (Review)
Review
Pathogens deploy an arsenal of virulence factors (VFs) to establish themselves within their infectious niche. The discovery of antimicrobial compounds and their development into therapeutics has made a monumental impact on human and microbial populations. Although humans have used antimicrobials for medicinal and agricultural purposes, microorganism populations have developed and shared resistance mechanisms to persevere in the face of classical antimicrobials. However, a positive substitute is antivirulence therapy; antivirulence therapeutics prevent or interrupt an infection by counteracting a pathogen's VFs. Their application can reduce the use of broad-spectrum antimicrobials and dampen the frequency with which resistant strains emerge. Here, we summarize the contribution of VFs to various acute and chronic infections. In correspondence with this, we provide an overview of the research and development of antivirulence strategies.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Humans; Quorum Sensing; Virulence; Virulence Factors
PubMed: 27313446
DOI: 10.2147/DDDT.S98939 -
Biomolecules Jun 2021Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small... (Review)
Review
Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small molecules and antibodies. Strategies to use components of the systems to design prophylactics have been less publicized despite vaccines being the preferred solution to dealing with bacterial infections. In the current review, strategies to design vaccines against selected pathogens are presented and connected to the biology of the system. The examples are given for , , , , and other human pathogens, and discussed in terms of effectiveness and long-term protection.
Topics: Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Secretion Systems; Bacterial Vaccines; Humans; Virulence
PubMed: 34203937
DOI: 10.3390/biom11060892 -
MSphere Oct 2023Functional traits are characteristics that affect the fitness and metabolic function of a microorganism. There is growing interest in using high-throughput methods to...
Functional traits are characteristics that affect the fitness and metabolic function of a microorganism. There is growing interest in using high-throughput methods to characterize bacterial pathogens based on functional virulence traits. Traditional methods that phenotype a single organism for a single virulence trait can be time consuming and labor intensive. Alternatively, machine learning of whole-genome sequences (WGS) has shown some success in predicting virulence. However, relying solely on WGS can miss functional traits, particularly for organisms lacking classical virulence factors. We propose that high-throughput assays for functional virulence trait identification should become a prominent method of characterizing bacterial pathogens on a population scale. This work is critical as we move from compiling lists of bacterial species associated with disease to pathogen-agnostic approaches capable of detecting novel microbes. We discuss six key areas of functional trait testing and how advancing high-throughput methods could provide a greater understanding of pathogens.
Topics: Bacteria; Virulence; Virulence Factors; Phenotype; Genome, Bacterial
PubMed: 37702517
DOI: 10.1128/msphere.00315-23 -
Molecular Plant Pathology May 2008The term virulence has a conflicting history among plant pathologists. Here we define virulence as the degree of damage caused to a host by parasite infection, assumed... (Review)
Review
The term virulence has a conflicting history among plant pathologists. Here we define virulence as the degree of damage caused to a host by parasite infection, assumed to be negatively correlated with host fitness, and pathogenicity the qualitative capacity of a parasite to infect and cause disease on a host. Selection may act on both virulence and pathogenicity, and their change in parasite populations can drive parasite evolution and host-parasite co-evolution. Extensive theoretical analyses of the factors that shape the evolution of pathogenicity and virulence have been reported in last three decades. Experimental work has not followed the path of theoretical analyses. Plant pathologists have shown greater interest in pathogenicity than in virulence, and our understanding of the molecular basis of pathogenicity has increased enormously. However, little is known regarding the molecular basis of virulence. It has been proposed that the mechanisms of recognition of parasites by hosts will have consequences for the evolution of pathogenicity, but much experimental work is still needed to test these hypotheses. Much theoretical work has been based on evidence from cellular plant pathogens. We review here the current experimental and observational evidence on which to test theoretical hypotheses or conjectures. We compare evidence from viruses and cellular pathogens, mostly fungi and oomycetes, which differ widely in genomic complexity and in parasitism. Data on the evolution of pathogenicity and virulence from viruses and fungi show important differences, and their comparison is necessary to establish the generality of hypotheses on pathogenicity and virulence evolution.
Topics: Animals; Evolution, Molecular; Fungi; Host-Pathogen Interactions; Plant Diseases; Plant Viruses; Plants; Virulence
PubMed: 18705877
DOI: 10.1111/j.1364-3703.2007.00460.x -
Molecular Plant Pathology Feb 2022Decay due to fungal infection is a major cause of postharvest losses in fruits. Acidic fungi may enhance their virulence by locally reducing the pH of the host. Several... (Review)
Review
Decay due to fungal infection is a major cause of postharvest losses in fruits. Acidic fungi may enhance their virulence by locally reducing the pH of the host. Several devastating postharvest fungi, such as Penicillium spp., Botrytis cinerea, and Sclerotinia sclerotiorum, can secrete gluconic acid, oxalic acid, or citric acid. Emerging evidence suggests that organic acids secreted by acidic fungi are important virulence factors. In this review, we summarized the research progress on the biosynthesis of organic acids, the role of the pH signalling transcription factor PacC in regulating organic acid, and the action mechanism of the main organic acid secreted via postharvest pathogenic fungi during infection of host tissues. This paper systematically demonstrates the relationships between tissue acidification and postharvest fungal pathogenicity, which will motivate the study of host-pathogen interactions and provide a better understanding of virulence mechanisms of the pathogens so as to design new technical strategies to prevent postharvest diseases.
Topics: Fruit; Fungi; Host-Pathogen Interactions; Penicillium; Virulence; Virulence Factors
PubMed: 34820999
DOI: 10.1111/mpp.13159 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2017Fungal pathogens represent an important group of human pathogenic microbes that lead to an unacceptably severe global burden especially due to exceptionally high... (Review)
Review
Fungal pathogens represent an important group of human pathogenic microbes that lead to an unacceptably severe global burden especially due to exceptionally high mortality. For many fungal pathogens, they are widespread saprophytes and human host is not the exclusive niche for their proliferation. Their exceptional capability to survive and thrive within infected host likely stems from their sophisticated strategies in adaptation to diverse biotic and abiotic stressors from natural niches or predators. Among these 'environmental pathogens', Cryptococcus neoformans as a model organism claims the lives of more than half a million annually. Some recent studies indicate that cryptococcal survival both inside and outside of hosts can be coordinated by a combination of social behaviors. In this review, we describe and discuss the social behaviors employed by C. neoformans and address their significant impact on biofilm formation, sexual reproduction and pathogenicity.
Topics: Adaptation, Physiological; Cryptococcosis; Cryptococcus neoformans; Humans; Microbial Interactions; Virulence
PubMed: 28956401
DOI: 10.13345/j.cjb.170128 -
Advances in Experimental Medicine and... 2010Sphingolipid involvement in infectious disease is a new and exciting branch of research. Various microbial pathogens have been shown to synthesize their own... (Review)
Review
Sphingolipid involvement in infectious disease is a new and exciting branch of research. Various microbial pathogens have been shown to synthesize their own sphingolipids and some have evolved methods to "hijack" host sphingolipids for their own use. For instance, Sphingomonas species are bacterial pathogens that lack the lipopolysaccharide component typical but instead contain glycosphingolipids (Kawahara 1991, 2006). In terms of sphingolipid signaling and function, perhaps the best-studied group of microbes is the pathogenic fungi. Pathogenic fungi still represent significant problems in human disease, despite treatments that have been used for decades. Because fungi are eukaryotic, drug targets in fungi can have many similarities to mammalian processes. This often leads to significant side effects of antifungal drugs that can be dose limiting in many patient populations. The search for fungal-specific drugs and the need for better understanding of cellular processes of pathogenic fungi has led to a large body of research on fungal signaling. One particularly interesting and rapidly growing field in this research is the involvement of fungal sphingolipid pathways in signaling and virulence. In this chapter, the research relating to sphingolipid signaling pathogenic fungi will be reviewed and summarized, in addition to highlighting pathways that show promise for future research.
Topics: Cryptococcus neoformans; Fungi; Humans; Models, Biological; Signal Transduction; Sphingolipids; Virulence
PubMed: 20919658
DOI: 10.1007/978-1-4419-6741-1_16 -
Genes Jul 2021RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to... (Review)
Review
RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to adaptive processes. RNA modifications play multiple functions since they can impact RNA base-pairings, recognition by proteins, decoding, as well as RNA structure and stability. However, their roles in stress, environmental adaptation and during infections caused by pathogenic bacteria have just started to be appreciated. With the development of modern technologies in mass spectrometry and deep sequencing, recent examples of modifications regulating host-pathogen interactions have been demonstrated. They show how RNA modifications can regulate immune responses, antibiotic resistance, expression of virulence genes, and bacterial persistence. Here, we illustrate some of these findings, and highlight the strategies used to characterize RNA modifications, and their potential for new therapeutic applications.
Topics: Bacteria; Host Adaptation; Host-Pathogen Interactions; RNA Processing, Post-Transcriptional; RNA, Bacterial; Virulence
PubMed: 34440299
DOI: 10.3390/genes12081125 -
Current Opinion in Microbiology Feb 2011Residing within the intestine is a large community of commensal organisms collectively termed the microbiota. This community generates a complex nutrient environment by... (Review)
Review
Residing within the intestine is a large community of commensal organisms collectively termed the microbiota. This community generates a complex nutrient environment by breaking down indigestible food products into metabolites that are used by both the host and the microbiota. Both the invading intestinal pathogen and the microbiota compete for these metabolites, which can shape both the composition of the flora, as well as susceptibility to infection. After infection is established, pathogen mediated inflammation alters the composition of the microbiota, which further shifts the makeup of metabolites in the gastrointestinal tract. A greater understanding of the interplay between the microbiota, the metabolites they generate, and susceptibility to enteric disease will enable the discovery of novel therapies against infectious disease.
Topics: Animals; Bacteria; Gastrointestinal Tract; Humans; Metagenome; Nutritional Physiological Phenomena; Virulence
PubMed: 21215681
DOI: 10.1016/j.mib.2010.12.012