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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 -
Virulence Dec 2021Mycoplasmas, the smallest bacteria lacking a cell wall, can cause various diseases in both humans and animals. Mycoplasmas harbor a variety of virulence factors that... (Review)
Review
Mycoplasmas, the smallest bacteria lacking a cell wall, can cause various diseases in both humans and animals. Mycoplasmas harbor a variety of virulence factors that enable them to overcome numerous barriers of entry into the host; using accessory proteins, mycoplasma adhesins can bind to the receptors or extracellular matrix of the host cell. Although the host immune system can eradicate the invading mycoplasma in most cases, a few sagacious mycoplasmas employ a series of invasion and immune escape strategies to ensure their continued survival within their hosts. For instance, capsular polysaccharides are crucial for anti-phagocytosis and immunomodulation. Invasive enzymes degrade reactive oxygen species, neutrophil extracellular traps, and immunoglobulins. Biofilm formation is important for establishing a persistent infection. During proliferation, successfully surviving mycoplasmas generate numerous metabolites, including hydrogen peroxide, ammonia and hydrogen sulfide; or secrete various exotoxins, such as community-acquired respiratory distress syndrome toxin, and hemolysins; and express various pathogenic enzymes, all of which have potent toxic effects on host cells. Furthermore, some inherent components of mycoplasmas, such as lipids, membrane lipoproteins, and even mycoplasma-generated superantigens, can exert a significant pathogenic impact on the host cells or the immune system. In this review, we describe the proposed virulence factors in the toolkit of notorious mycoplasmas to better understand the pathogenic features of these bacteria, along with their pathogenic mechanisms.
Topics: Animals; Biofilms; Host-Pathogen Interactions; Humans; Mice; Mycoplasma; Phagocytosis; Virulence; Virulence Factors
PubMed: 33704021
DOI: 10.1080/21505594.2021.1889813 -
European Journal of Clinical... Nov 2017In recent years, whole-genome sequencing (WGS) has been perceived as a technology with the potential to revolutionise clinical microbiology. Herein, we reviewed the... (Review)
Review
In recent years, whole-genome sequencing (WGS) has been perceived as a technology with the potential to revolutionise clinical microbiology. Herein, we reviewed the literature on the use of WGS for the most commonly encountered pathogens in clinical microbiology laboratories: Escherichia coli and other Enterobacteriaceae, Staphylococcus aureus and coagulase-negative staphylococci, streptococci and enterococci, mycobacteria and Chlamydia trachomatis. For each pathogen group, we focused on five different aspects: the genome characteristics, the most common genomic approaches and the clinical uses of WGS for (i) typing and outbreak analysis, (ii) virulence investigation and (iii) in silico antimicrobial susceptibility testing. Of all the clinical usages, the most frequent and straightforward usage was to type bacteria and to trace outbreaks back. A next step toward standardisation was made thanks to the development of several new genome-wide multi-locus sequence typing systems based on WGS data. Although virulence characterisation could help in various particular clinical settings, it was done mainly to describe outbreak strains. An increasing number of studies compared genotypic to phenotypic antibiotic susceptibility testing, with mostly promising results. However, routine implementation will preferentially be done in the workflow of particular pathogens, such as mycobacteria, rather than as a broadly applicable generic tool. Overall, concrete uses of WGS in routine clinical microbiology or infection control laboratories were done, but the next big challenges will be the standardisation and validation of the procedures and bioinformatics pipelines in order to reach clinical standards.
Topics: Bacteria; Base Sequence; Genome, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Multilocus Sequence Typing; Virulence
PubMed: 28639162
DOI: 10.1007/s10096-017-3024-6 -
BMC Veterinary Research Jul 2022Pasteurella multocida is one of the most significant pathogens for a number of animals. In rabbits, the infection is generally associated with the P. multocida...
BACKGROUND
Pasteurella multocida is one of the most significant pathogens for a number of animals. In rabbits, the infection is generally associated with the P. multocida serogroups A and D, and the knowledge about the serogroup F is limited. In the present study, a P. multocida serogroup F isolate designated s4 was recovered from the lungs of rabbits died of respiratory disease in Fujian, in the southeast of China. The pathogenicity and genomic features of the s4 were then determined.
RESULTS
The serotype and sequence type of s4 were F:L3 and ST12, respectively. The s4 was pathogenic for rabbits, but it was a low virulent strain comparing to the previously reported highly pathogenic P. multocida serogroup F strains J-4103, C21724H3km7, P-4218 and HN07. The whole genome of the s4 was then sequenced to understand the genomic basis for pathogenicity. Particularly, a large-sized fragment of approximate 275 kb in length was truncated from the chromosome to form a plasmid. Moreover, the in-frame deletion of natC and N-terminal redundance of gatF would resulted in the production of a mutant L3 outer core structure that was distinct from those of the other P. multocida strains belonging to the lipopolysaccharide genotype L3. We deduced that these features detected in the genome of s4 might impair the pathogenicity of the bacterium.
CONCLUSIONS
This study evaluated the pathogenicity and determined the genomic features of the rabbit sourced P. multocida serogroup F isolate s4, the observations and findings would helpful for the understanding of the pathogenicity variability and genetic diversity of P. multocida.
Topics: Animals; Genomics; Pasteurella Infections; Pasteurella multocida; Rabbits; Serogroup; Virulence
PubMed: 35869529
DOI: 10.1186/s12917-022-03381-7 -
The ISME Journal Aug 2016Many micro-organisms employ a parasitic lifestyle and, through their antagonistic interactions with host populations, have major impacts on human, agricultural and... (Review)
Review
Many micro-organisms employ a parasitic lifestyle and, through their antagonistic interactions with host populations, have major impacts on human, agricultural and natural ecosystems. Most pathogens are likely to host parasites of their own, that is, hyperparasites, but how nested chains of parasites impact on disease dynamics is grossly neglected in the ecological and evolutionary literature. In this minireview we argue that the diversity and dynamics of micro-hyperparasites are an important component of natural host-pathogen systems. We use the current literature from a handful of key systems to show that observed patterns of pathogen virulence and disease dynamics may well be influenced by hyperparasites. Exploring these factors will shed light on many aspects of microbial ecology and disease biology, including resistance-virulence evolution, apparent competition, epidemiology and ecosystem stability. Considering the importance of hyperparasites in natural populations will have applied consequences for the field of biological control and therapeutic science, where hyperparastism is employed as a control mechanism but not necessarily ecologically understood.
Topics: Animals; Biological Evolution; Ecology; Ecosystem; Host-Pathogen Interactions; Humans; Parasites; Virulence
PubMed: 26784356
DOI: 10.1038/ismej.2015.247 -
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 -
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 -
Trends in Microbiology May 2020Bacterial pathogens employ diverse fitness and virulence mechanisms to gain an advantage in competitive niches. These lifestyle-specific traits require integration into... (Review)
Review
Bacterial pathogens employ diverse fitness and virulence mechanisms to gain an advantage in competitive niches. These lifestyle-specific traits require integration into the regulatory network of the cell and are often controlled by pre-existing transcription factors. In this review, we highlight recent advances that have been made in characterizing this regulatory flexibility in prominent members of the Enterobacteriaceae. We focus on the direct global interactions between transcription factors and their target genes in pathogenic Escherichia coli and Salmonella revealed using chromatin immunoprecipitation coupled with next-generation sequencing. Furthermore, the implications and advantages of such regulatory adaptations in benefiting distinct pathogenic lifestyles are discussed.
Topics: Chromatin Immunoprecipitation; Escherichia coli; Escherichia coli Infections; Gene Expression Regulation, Bacterial; High-Throughput Nucleotide Sequencing; Salmonella; Salmonella Infections; Transcription Factors; Transcription, Genetic; Virulence
PubMed: 32298614
DOI: 10.1016/j.tim.2020.01.002 -
International Journal of Molecular... Feb 2023The growth-defense trade-off in plants is a phenomenon whereby plants must balance the allocation of their resources between developmental growth and defense against... (Review)
Review
The growth-defense trade-off in plants is a phenomenon whereby plants must balance the allocation of their resources between developmental growth and defense against attack by pests and pathogens. Consequently, there are a series of points where growth signaling can negatively regulate defenses and where defense signaling can inhibit growth. Light perception by various photoreceptors has a major role in the control of growth and thus many points where it can influence defense. Plant pathogens secrete effector proteins to manipulate defense signaling in their hosts. Evidence is emerging that some of these effectors target light signaling pathways. Several effectors from different kingdoms of life have converged on key chloroplast processes to take advantage of regulatory crosstalk. Moreover, plant pathogens also perceive and react to light in complex ways to regulate their own growth, development, and virulence. Recent work has shown that varying light wavelengths may provide a novel way of controlling or preventing disease outbreaks in plants.
Topics: Plants; Light Signal Transduction; Signal Transduction; Virulence; Chloroplasts; Plant Diseases; Plant Immunity
PubMed: 36835216
DOI: 10.3390/ijms24043803 -
Journal of Virology Jul 2023Porcine epidemic diarrhea virus is a swine pathogen that has been responsible for significant animal and economic losses worldwide in recent years. In this manuscript,...
Porcine epidemic diarrhea virus is a swine pathogen that has been responsible for significant animal and economic losses worldwide in recent years. In this manuscript, we report the generation of a reverse genetics system C(RGS) for the highly virulent US PEDV strain Minnesota (PEDV-MN; GenBank accession number KF468752), which was based on the assembly and cloning of synthetic DNA, using vaccinia virus as a cloning vector. Viral rescue was only possible following the substitution of 2 nucleotides within the 5'UTR and 2 additional nucleotides within the spike gene, based on the sequence of the cell culture-adapted strains. Besides displaying a highly pathogenic phenotype in newborn piglets, in comparison with the parental virus, the rescued recombinant PEDV-MN was used to confirm that the PEDV spike gene has an important role in PEDV virulence and that the impact of an intact PEDV ORF3 on viral pathogenicity is modest. Moreover, a chimeric virus with a TGEV spike gene in the PEDV backbone generated with RGS was able to replicate efficiently and could be readily transmitted between piglets. Although this chimeric virus did not cause severe disease upon the initial infection of piglets, there was evidence of increasing pathogenicity upon transmission to contact piglets. The RGS described in this study constitutes a powerful tool with which to study PEDV pathogenesis and can be used to generate vaccines against porcine enteric coronaviruses. PEDV is a swine pathogen that is responsible for significant animal and economic losses worldwide. Highly pathogenic variants can lead to a mortality rate of up to 100% in newborn piglets. The generation of a reverse genetics system for a highly virulent PEDV strain originating from the United States is an important step in phenotypically characterizing PEDV. The synthetic PEDV mirrored the authentic isolate and displayed a highly pathogenic phenotype in newborn piglets. With this system, it was possible to characterize potential viral virulence factors. Our data revealed that an accessory gene (ORF3) has a limited impact on pathogenicity. However, as it is also now known for many coronaviruses, the PEDV spike gene is one of the main determinants of pathogenicity. Finally, we show that the spike gene of another porcine coronavirus, namely, TGEV, can be accommodated in the PEDV genome background, suggesting that similar viruses can emerge in the field via recombination.
Topics: Animals; United States; Swine; Virulence; Porcine epidemic diarrhea virus; Spike Glycoprotein, Coronavirus; Swine Diseases; Reverse Genetics; Coronavirus Infections; Nucleotides; Diarrhea
PubMed: 37358450
DOI: 10.1128/jvi.01964-22