Transmission, infection, and pathogenesis

2021 ◽  
pp. 213-240
Author(s):  
Paul Schmid-Hempel
Keyword(s):  
Virulence Factors ◽  
Host Manipulation ◽  
Tissue Destruction ◽  
New Host ◽  
Successful Transmission ◽  
Transmission Process ◽  
Infective Dose ◽  
Process Based Models

Transmission is a key process for parasites. Different routes (e.g. faecal–oral) and modes (e.g. by aerosols or vectors) exist. A major context is vertical (to offspring) or horizontal (all other) transmission. All components of the transmission process evolve. Successful transmission includes the infection of a new host. Macroparasites typically infect as individuals, but microparasites need an infective dose. Doses vary enormously among parasites. Various models describe variation in infective dose. Process-based models assume random colonization, co-operative parasite manipulation, or are focused on early dynamics. With the processes of pathogenesis (e.g. tissue destruction, reducing host capacities), damage to the host emerges. Virulence factors are important mediators of parasite success and often involved in host manipulation and pathogenesis, including immunopathology.

scholarly journals A Salmonella Typhi RNA thermosensor regulates virulence factors and innate immune evasion in response to host temperature

2021 ◽  
Vol 17 (3) ◽  
pp. e1009345
Author(s):  
Susan M. Brewer ◽  
Christian Twittenhoff ◽  
Jens Kortmann ◽  
Sky W. Brubaker ◽  
Jared Honeycutt ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Bacterial Pathogens ◽  
Innate Immune ◽  
New Host ◽  
Factor Expression

Sensing and responding to environmental signals is critical for bacterial pathogens to successfully infect and persist within hosts. Many bacterial pathogens sense temperature as an indication they have entered a new host and must alter their virulence factor expression to evade immune detection. Using secondary structure prediction, we identified an RNA thermosensor (RNAT) in the 5’ untranslated region (UTR) of tviA encoded by the typhoid fever-causing bacterium Salmonella enterica serovar Typhi (S. Typhi). Importantly, tviA is a transcriptional regulator of the critical virulence factors Vi capsule, flagellin, and type III secretion system-1 expression. By introducing point mutations to alter the mRNA secondary structure, we demonstrate that the 5’ UTR of tviA contains a functional RNAT using in vitro expression, structure probing, and ribosome binding methods. Mutational inhibition of the RNAT in S. Typhi causes aberrant virulence factor expression, leading to enhanced innate immune responses during infection. In conclusion, we show that S. Typhi regulates virulence factor expression through an RNAT in the 5’ UTR of tviA. Our findings demonstrate that limiting inflammation through RNAT-dependent regulation in response to host body temperature is important for S. Typhi’s “stealthy” pathogenesis.

scholarly journals The Toxoplasma gondii Rhoptry Kinome Is Essential for Chronic Infection

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Barbara A. Fox ◽  
Leah M. Rommereim ◽  
Rebekah B. Guevara ◽  
Alejandra Falla ◽  
Miryam Andrea Hortua Triana ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Toxoplasma Gondii ◽  
Virulence Factors ◽  
Chronic Infection ◽  
Parasitophorous Vacuole ◽  
Acute Infection ◽  
Host Cells ◽  
Type Ii ◽  
Host Manipulation ◽  
Parasite Survival

ABSTRACT    Ingestion of the obligate intracellular protozoan parasite Toxoplasma gondii causes an acute infection that leads to chronic infection of the host. To facilitate the acute phase of the infection, T. gondii manipulates the host response by secreting rhoptry organelle proteins (ROPs) into host cells during its invasion. A few key ROP proteins with signatures of kinases or pseudokinases (ROPKs) act as virulence factors that enhance parasite survival against host gamma interferon-stimulated innate immunity. However, the roles of these and other ROPK proteins in establishing chronic infection have not been tested. Here, we deleted 26 ROPK gene loci encoding 31 unique ROPK proteins of type II T. gondii and show that numerous ROPK proteins influence the development of chronic infection. Cyst burdens were increased in the Δ rop16 knockout strain or moderately reduced in 11 ROPK knockout strains. In contrast, deletion of ROP5 , ROP17 , ROP18 , ROP35 , or ROP38 / 29 / 19 ( ROP38 , ROP29 , and ROP19 ) severely reduced cyst burdens. Δ rop5 and Δ rop18 knockout strains were less resistant to host immunity-related GTPases (IRGs) and exhibited >100-fold-reduced virulence. ROP18 kinase activity and association with the parasitophorous vacuole membrane were necessary for resistance to host IRGs. The Δ rop17 strain exhibited a >12-fold defect in virulence; however, virulence was not affected in the Δ rop35 or Δ rop38 / 29 / 19 strain. Resistance to host IRGs was not affected in the Δ rop17 , Δ rop35 , or Δ rop38 / 29 / 19 strain. Collectively, these findings provide the first definitive evidence that the type II T. gondii ROPK proteome functions as virulence factors and facilitates additional mechanisms of host manipulation that are essential for chronic infection and transmission of T. gondii . IMPORTANCE Reactivation of chronic Toxoplasma gondii infection in individuals with weakened immune systems causes severe toxoplasmosis. Existing treatments for toxoplasmosis are complicated by adverse reactions to chemotherapy. Understanding key parasite molecules required for chronic infection provides new insights into potential mechanisms that can interrupt parasite survival or persistence in the host. This study reveals that key secreted rhoptry molecules are used by the parasite to establish chronic infection of the host. Certain rhoptry proteins were found to be critical virulence factors that resist innate immunity, while other rhoptry proteins were found to influence chronic infection without affecting virulence. This study reveals that rhoptry proteins utilize multiple mechanisms of host manipulation to establish chronic infection of the host. Targeted disruption of parasite rhoptry proteins involved in these biological processes opens new avenues to interfere with chronic infection with the goal to either eliminate chronic infection or to prevent recrudescent infections.

scholarly journals PORPHYROMONAS GINGIVALIS E PERIODONTITE CRÔNICA - AVANÇOS RECENTES

2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Victor Hugo Rocha Leon ◽  
Ellen Karla Nobre dos Santos-Lima ◽  
Ana Carla Montino Pimentel ◽  
Patricia Mares de Miranda ◽  
Paulo Cirino De Carvalho Filho ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Virulence Factors ◽  
Chronic Periodontitis ◽  
Cellular Response ◽  
Current Knowledge ◽  
Periodontal Diseases ◽  
Tissue Destruction ◽  
Inflammatory State ◽  
Cell Death Mechanisms

Periodontal disease is multifactorial and it affects the tissues surrounding the teeth. Its etiology includes microrganisms as Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans. This work aimed to discuss the role of Porphyromonas gingivalis in chronic periodontitis. The electronic bases PubMed, BIREME and SciELO were used to search for historical aspects and studies published between 2000 and 2015, using the following descriptors in Portuguese and English: “Chronic periodontitis, Porphyromonas gingivalis” and “Virulence factors”. 205 articles were found and 24 were included. Records on periodontal diseases from the early civilization to the present day were found. Its prevalence in the world’s population remains high and several studies report the pathogenesis of the disease. P. gingivalis is able to induce humoral and cellular response in infected individuals. Studies on its escape mechanisms and virulence factors report tissue breakdown consequent to immuno-inflammatory exacerbated response in the host which may evolve into edentulism. Studies of the immune response to P. gingivalis suggest its role in perpetuation of the inflammatory state by interfering with cytokines production and cell death mechanisms in the host’s cells, resulting in tissue destruction. The current knowledge about mechanisms of infection and virulence factors of P. gingivalis indicate its role as a key component in chronic periodontitis.

scholarly journals Delivery of Toxins and Effectors by Bacterial Membrane Vesicles

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 845
Author(s):  
Adrian Macion ◽  
Agnieszka Wyszyńska ◽  
Renata Godlewska
Keyword(s):  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Oral Bacteria ◽  
Host Cells ◽  
Target Cells ◽  
Tissue Destruction ◽  
Secretion Systems ◽  
The Central Nervous System

Pathogenic bacteria interact with cells of their host via many factors. The surface components, i.e., adhesins, lipoproteins, LPS and glycoconjugates, are particularly important in the initial stages of colonization. They enable adhesion and multiplication, as well as the formation of biofilms. In contrast, virulence factors such as invasins and toxins act quickly to damage host cells, causing tissue destruction and, consequently, organ dysfunction. These proteins must be exported from the bacterium and delivered to the host cell in order to function effectively. Bacteria have developed a number of one- and two-step secretion systems to transport their proteins to target cells. Recently, several authors have postulated the existence of another transport system (sometimes called “secretion system type zero”), which utilizes extracellular structures, namely membrane vesicles (MVs). This review examines the role of MVs as transporters of virulence factors and the interaction of toxin-containing vesicles and other protein effectors with different human cell types. We focus on the unique ability of vesicles to cross the blood–brain barrier and deliver protein effectors from intestinal or oral bacteria to the central nervous system.

scholarly journals Pyroptosis-Mediated Periodontal Disease

2021 ◽  
Vol 23 (1) ◽  
pp. 372
Author(s):  
Mariane Beatriz Sordi ◽  
Ricardo de Souza Magini ◽  
Layla Panahipour ◽  
Reinhard Gruber
Keyword(s):  
Periodontal Disease ◽  
Virulence Factors ◽  
Tissue Homeostasis ◽  
Host Responses ◽  
Caspase Activation ◽  
Tissue Destruction ◽  
Periodontal Tissues ◽  
Cellular Events ◽  
Pathological Mechanism ◽  
Potential Strategy

Pyroptosis is a caspase-dependent process relevant to the understanding of beneficial host responses and medical conditions for which inflammation is central to the pathophysiology of the disease. Pyroptosis has been recently suggested as one of the pathways of exacerbated inflammation of periodontal tissues. Hence, this focused review aims to discuss pyroptosis as a pathological mechanism in the cause of periodontitis. The included articles presented similarities regarding methods, type of cells applied, and cell stimulation, as the outcomes also point to the same direction considering the cellular events. The collected data indicate that virulence factors present in the diseased periodontal tissues initiate the inflammasome route of tissue destruction with caspase activation, cleavage of gasdermin D, and secretion of interleukins IL-1β and IL-18. Consequently, removing periopathogens’ virulence factors, triggering pyroptosis, is a potential strategy to combat periodontal disease and regain tissue homeostasis.

scholarly journals An aphid host-responsive RNA transcript that migrates systemically in plants promotes aphid reproduction

2019 ◽  
Author(s):  
Yazhou Chen ◽  
Archana Singh ◽  
Gemy G. Kaithakottill ◽  
Thomas C. Mathers ◽  
Matteo Gravino ◽  
...  
Keyword(s):  
Plant Species ◽  
Virulence Factors ◽  
Myzus Persicae ◽  
Plant Pathogens ◽  
Tandem Repeats ◽  
Vascular Tissue ◽  
Green Peach Aphid ◽  
New Host ◽  
Diverse Range ◽  
Sap Feeding

ABSTRACTAphids are sap-feeding insects that colonize a broad range of plant species and often cause feeding damage and transmit plant pathogens, including bacteria, viruses and viroids. These insects feed from the plant vascular tissue, predominantly the phloem. However, it remains largely unknown how aphids, and other sap-feeding insects, establish intimate long-term interactions with plants. To identify aphid virulence factors, we took advantage of the ability of the green peach aphid Myzus persicae to colonize divergent plant species. We found that a M. persicae clone of near-identical females establishes stable colonies on nine plant species of five representative plant eudicot and monocot families that span the angiosperm phylogeny. Members of the novel aphid Ya family are differentially expressed in aphids on the nine plant species, are co-regulated and organized as tandem repeats in aphid genomes. Interestingly, aphids translocate Ya transcripts into plants and some transcripts migrate systemically within several plant species. RNAi-mediated knock down of Ya genes reduces M. persicae fecundity and M. persicae produces more progeny on transgenic plants that heterologously produce one of the systemically migrating Ya transcripts as a long non-coding (lnc)RNA. Taken together, our work led to the discovery of a new host-responsive aphid gene family that operate as virulence factors. Transcripts of this family translocate into plants, including a lncRNA that migrates systemically and promotes aphid reproduction.Significance StatementThe green peach aphid Myzus persicae causes yield losses of a diverse range of economically important crops primarily as a vector of more than 100 different plant pathogens. We found that a single genotype of M. persicae is able to colonize nine plant species, including diverse dicots and maize, indicating that this aphid is truly polyphagous. Members of a new aphid Ya family undergoes coordinated expression changes in M. persicae depending on the plant species. The aphids translocate Ya transcripts into plants during feeding and these RNAs migrate to systemic leaves. Moreover, heterologous in planta expression of M. persicae Ya1 as a long non-coding RNA promotes aphid reproduction. Our findings indicate that cross kingdom deployment of RNA is more common than thought.

The Intravascular Generation of Fibrinogen Derivatives and the Blood Vessel Wall in Venous Thrombosis and Disseminated Intravascular Coagulation

1977 ◽  
Vol 38 (04) ◽  
pp. 0831-0849 ◽  
Author(s):  
Gwendolyn J. Stewart
Keyword(s):  
Blood Vessel ◽  
Venous Thrombosis ◽  
Vessel Wall ◽  
Fluid Phase ◽  
Primary Site ◽  
Blood Vessel Wall ◽  
Fibrin Deposition ◽  
Tissue Destruction ◽  
Fibrin Formation ◽  
Rich Material

SummaryBoth deep venous thrombosis and DIC are intermediate mechanisms of disease – both are a consequence of the deposition of fibrin-rich material in blood vessels some distance from the primary site of tissue destruction. The great difference in the sites of fibrin deposition may depend on the extent and site of activation of the clotting mechanism. DIC likely occurs in the fluid phase of the blood as a consequence of massive fibrin formation while thrombosis results from limited fibrin formation at the interface between blood and vessel wall. Leukocytes may be essential for attaching thrombi to the vessel wall in many places.

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