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International Journal of Molecular... Jul 2023is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility of this pathogen are powered by a wide array of... (Review)
Review
is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility of this pathogen are powered by a wide array of virulence factors necessary in different steps of the infection process. This includes factors involved in bacterial motility and attachment, biofilm formation, the production and secretion of extracellular invasive enzymes and exotoxins, the production of toxic secondary metabolites, and the acquisition of iron. Expression of these virulence factors during infection is tightly regulated, which allows their production only when they are needed. This process optimizes host colonization and virulence. In this work, we review the intricate network of transcriptional regulators that control the expression of virulence factors in , including one- and two-component systems and σ factors. Because inhibition of virulence holds promise as a target for new antimicrobials, blocking the regulators that trigger the production of virulence determinants in is a promising strategy to fight this clinically relevant pathogen.
Topics: Humans; Virulence; Pseudomonas aeruginosa; Virulence Factors; Exotoxins; Quorum Sensing; Biofilms; Bacterial Proteins; Pseudomonas Infections
PubMed: 37569271
DOI: 10.3390/ijms241511895 -
Annual Review of Microbiology Sep 2023Bacteria are single-celled organisms that carry a comparatively small set of genetic information, typically consisting of a few thousand genes that can be selectively... (Review)
Review
Bacteria are single-celled organisms that carry a comparatively small set of genetic information, typically consisting of a few thousand genes that can be selectively activated or repressed in an energy-efficient manner and transcribed to encode various biological functions in accordance with environmental changes. Research over the last few decades has uncovered various ingenious molecular mechanisms that allow bacterial pathogens to sense and respond to different environmental cues or signals to activate or suppress the expression of specific genes in order to suppress host defenses and establish infections. In the setting of infection, pathogenic bacteria have evolved various intelligent mechanisms to reprogram their virulence to adapt to environmental changes and maintain a dominant advantage over host and microbial competitors in new niches. This review summarizes the bacterial virulence programming mechanisms that enable pathogens to switch from acute to chronic infection, from local to systemic infection, and from infection to colonization. It also discusses the implications of these findings for the development of new strategies to combat bacterial infections.
Topics: Virulence; Bacteria
PubMed: 37406345
DOI: 10.1146/annurev-micro-032521-025954 -
International Journal of Molecular... Dec 2023stands as one of the most pervasive pathogens given its morbidity and mortality worldwide due to its roles as an infectious agent that causes a wide variety of diseases... (Review)
Review
stands as one of the most pervasive pathogens given its morbidity and mortality worldwide due to its roles as an infectious agent that causes a wide variety of diseases ranging from moderately severe skin infections to fatal pneumonia and sepsis. produces a variety of exotoxins that serve as important virulence factors in -related infectious diseases and food poisoning in both humans and animals. For example, staphylococcal enterotoxins (SEs) produced by induce staphylococcal foodborne poisoning; toxic shock syndrome toxin-1 (TSST-1), as a typical superantigen, induces toxic shock syndrome; hemolysins induce cell damage in erythrocytes and leukocytes; and exfoliative toxin induces staphylococcal skin scalded syndrome. Recently, Panton-Valentine leucocidin, a cytotoxin produced by community-associated methicillin-resistant (CA-MRSA), has been reported, and new types of SEs and staphylococcal enterotoxin-like toxins (SEls) were discovered and reported successively. This review addresses the progress of and novel insights into the molecular structure, biological activities, and pathogenicity of both the classic and the newly identified exotoxins produced by .
Topics: Animals; Humans; Staphylococcus aureus; Virulence; Methicillin-Resistant Staphylococcus aureus; Exotoxins; Staphylococcal Infections
PubMed: 38203566
DOI: 10.3390/ijms25010395 -
International Journal of Molecular... Sep 2023Staphylococci are major causes of infections in mammals. Mammals are colonized by diverse staphylococcal species, often with moderate to strong host specificity, and... (Review)
Review
Staphylococci are major causes of infections in mammals. Mammals are colonized by diverse staphylococcal species, often with moderate to strong host specificity, and colonization is a common source of infection. Staphylococcal infections of animals not only are of major importance for animal well-being but have considerable economic consequences, such as in the case of staphylococcal mastitis, which costs billions of dollars annually. Furthermore, pet animals can be temporary carriers of strains infectious to humans. Moreover, antimicrobial resistance is a great concern in livestock infections, as there is considerable antibiotic overuse, and resistant strains can be transferred to humans. With the number of working antibiotics continuously becoming smaller due to the concomitant spread of resistant strains, alternative approaches, such as anti-virulence, are increasingly being investigated to treat staphylococcal infections. For this, understanding the virulence mechanisms of animal staphylococcal pathogens is crucial. While many virulence factors have similar functions in humans as animals, there are increasingly frequent reports of host-specific virulence factors and mechanisms. Furthermore, we are only beginning to understand virulence mechanisms in animal-specific staphylococcal pathogens. This review gives an overview of animal infections caused by staphylococci and our knowledge about the virulence mechanisms involved.
Topics: Animals; Female; Humans; Virulence; Staphylococcus; Staphylococcal Infections; Anti-Bacterial Agents; Virulence Factors; Mammals; Microbial Sensitivity Tests
PubMed: 37834035
DOI: 10.3390/ijms241914587 -
Seminars in Cell & Developmental Biology 2023Downy mildews are obligate oomycete pathogens that attack a wide range of plants and can cause significant economic impacts on commercial crops and ornamental plants.... (Review)
Review
Downy mildews are obligate oomycete pathogens that attack a wide range of plants and can cause significant economic impacts on commercial crops and ornamental plants. Traditionally, downy mildew disease control relied on an integrated strategies, that incorporate cultural practices, deployment of resistant cultivars, crop rotation, application of contact and systemic pesticides, and biopesticides. Recent advances in genomics provided data that significantly advanced understanding of downy mildew evolution, taxonomy and classification. In addition, downy mildew genomics also revealed that these obligate oomycetes have reduced numbers of virulence factor genes in comparison to hemibiotrophic and necrotrophic oomycetes. However, downy mildews do deploy significant arrays of virulence proteins, including so-called RXLR proteins that promote virulence or are recognized as avirulence factors. Pathogenomics are being applied to downy mildew population studies to determine the genetic diversity within the downy mildew populations and manage disease by selection of appropriate varieties and management strategies. Genome editing technologies have been used to manipulate host disease susceptibility genes in different plants including grapevine and sweet basil and thereby provide new soucres of resistance genes against downy mildews. Previously, it has proved difficult to transform and manipulate downy mildews because of their obligate lifestyle. However, recent exploitation of RNA interference machinery through Host-Induced Gene Silencing (HIGS) and Spray-Induced Gene Silencing (SIGS) indicate that functional genomics in downy mildews is now possible. Altogether, these breakthrough technologies and attendant fundamental understanding will advance our ability to mitigate downy mildew diseases.
Topics: Oomycetes; Genomics; Plants; Virulence
PubMed: 36670035
DOI: 10.1016/j.semcdb.2023.01.010 -
Frontiers in Immunology 2023Dermatophytosis is a common superficial infection caused by dermatophytes, a group of pathogenic keratinophilic fungi. Apart from invasion against skin barrier, host... (Review)
Review
Dermatophytosis is a common superficial infection caused by dermatophytes, a group of pathogenic keratinophilic fungi. Apart from invasion against skin barrier, host immune responses to dermatophytes could also lead to pathologic inflammation and tissue damage to some extent. Therefore, it is of great help to understand the pathogenesis of dermatophytes, including fungal virulence factors and anti-pathogen immune responses. This review aims to summarize the recent advances in host-fungal interactions, focusing on the mechanisms of anti-fungal immunity and the relationship between immune deficiency and chronic dermatophytosis, in order to facilitate novel diagnostic and therapeutic approaches to improve the outcomes of these patients.
Topics: Humans; Arthrodermataceae; Dermatomycoses; Virulence; Tinea; Immunity
PubMed: 38022599
DOI: 10.3389/fimmu.2023.1285887 -
PLoS Pathogens Dec 2023Candida auris recently emerged as an urgent public health threat, causing outbreaks of invasive infections in healthcare settings throughout the world. This fungal... (Review)
Review
Candida auris recently emerged as an urgent public health threat, causing outbreaks of invasive infections in healthcare settings throughout the world. This fungal pathogen persists on the skin of patients and on abiotic surfaces despite antiseptic and decolonization attempts. The heightened capacity for skin colonization and environmental persistence promotes rapid nosocomial spread. Following skin colonization, C. auris can gain entrance to the bloodstream and deeper tissues, often through a wound or an inserted medical device, such as a catheter. C. auris possesses a variety of virulence traits, including the capacity for biofilm formation, production of adhesins and proteases, and evasion of innate immune responses. In this review, we highlight the interactions of C. auris with the host, emphasizing the intersection of laboratory studies and clinical observations.
Topics: Humans; Candida; Candidiasis; Virulence; Candida auris; Disease Outbreaks; Antifungal Agents
PubMed: 38127686
DOI: 10.1371/journal.ppat.1011843 -
Proceedings of the National Academy of... Jul 2023Phase variation induced by insertions and deletions (INDELs) in genomic homopolymeric tracts (HT) can silence and regulate genes in pathogenic bacteria, but this process...
Phase variation induced by insertions and deletions (INDELs) in genomic homopolymeric tracts (HT) can silence and regulate genes in pathogenic bacteria, but this process is not characterized in MTBC ( complex) adaptation. We leverage 31,428 diverse clinical isolates to identify genomic regions including phase-variants under positive selection. Of 87,651 INDEL events that emerge repeatedly across the phylogeny, 12.4% are phase-variants within HTs (0.02% of the genome by length). We estimated the in-vitro frameshift rate in a neutral HT at 100× the neutral substitution rate at [Formula: see text] frameshifts/HT/year. Using neutral evolution simulations, we identified 4,098 substitutions and 45 phase-variants to be putatively adaptive to MTBC ( < 0.002). We experimentally confirm that a putatively adaptive phase-variant alters the expression of a critical mediator of ESX-1-dependent virulence. Our evidence supports the hypothesis that phase variation in the ESX-1 system of MTBC can act as a toggle between antigenicity and survival in the host.
Topics: Mycobacterium tuberculosis; Phase Variation; Genomics; Adaptation, Physiological; Virulence; Phylogeny; Genome, Bacterial
PubMed: 37399390
DOI: 10.1073/pnas.2301394120 -
Virulence Dec 2024Heartland virus (HRTV), an emerging tick-borne pathogenic bunyavirus, has been a concern since 2012, with an increasing incidence, expanding geographical distribution,... (Review)
Review
Heartland virus (HRTV), an emerging tick-borne pathogenic bunyavirus, has been a concern since 2012, with an increasing incidence, expanding geographical distribution, and high pathogenicity in the United States. Infection from HRTV results in fever, thrombocytopenia, and leucopenia in humans, and in some cases, symptoms can progress to severe outcomes, including haemorrhagic disease, multi-organ failure, and even death. Currently, no vaccines or antiviral drugs are available for treatment of the HRTV disease. Moreover, little is known about HRTV-host interactions, viral replication mechanisms, pathogenesis and virulence, further hampering the development of vaccines and antiviral interventions. Here, we aimed to provide a brief review of HRTV epidemiology, molecular biology, pathogenesis and virulence on the basis of published article data to better understand this virus and provide clues for further study.
Topics: Humans; Virulence; Animals; Virus Replication; Bunyaviridae Infections; Thogotovirus; United States; Host-Pathogen Interactions; Bunyaviridae
PubMed: 38712703
DOI: 10.1080/21505594.2024.2348252 -
Microbiology and Molecular Biology... Sep 2023Cells adjust growth and metabolism to nutrient availability. Having access to a variety of carbon sources during infection of their animal hosts, facultative... (Review)
Review
Cells adjust growth and metabolism to nutrient availability. Having access to a variety of carbon sources during infection of their animal hosts, facultative intracellular pathogens must efficiently prioritize carbon utilization. Here, we discuss how carbon source controls bacterial virulence, with an emphasis on serovar Typhimurium, which causes gastroenteritis in immunocompetent humans and a typhoid-like disease in mice, and propose that virulence factors can regulate carbon source prioritization by modifying cellular physiology. On the one hand, bacterial regulators of carbon metabolism control virulence programs, indicating that pathogenic traits appear in response to carbon source availability. On the other hand, signals controlling virulence regulators may impact carbon source utilization, suggesting that stimuli that bacterial pathogens experience within the host can directly impinge on carbon source prioritization. In addition, pathogen-triggered intestinal inflammation can disrupt the gut microbiota and thus the availability of carbon sources. By coordinating virulence factors with carbon utilization determinants, pathogens adopt metabolic pathways that may not be the most energy efficient because such pathways promote resistance to antimicrobial agents and also because host-imposed deprivation of specific nutrients may hinder the operation of certain pathways. We propose that metabolic prioritization by bacteria underlies the pathogenic outcome of an infection.
Topics: Mice; Animals; Humans; Virulence; Appetite; Bacteria; Salmonella typhimurium; Virulence Factors; Carbon; Bacterial Proteins
PubMed: 37358444
DOI: 10.1128/mmbr.00198-22