scholarly journals The Invasin and Complement-Resistance Protein Rck of Salmonella is More Widely Distributed than Previously Expected

2021 ◽  
Author(s):  
Michael Koczerka ◽  
Pierre-Emmanuel Douarre ◽  
Florent Kempf ◽  
Sébastien Holbert ◽  
Michel-Yves Mistou ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Foodborne Pathogen ◽  
Infected Host ◽  
Content Type ◽  
Complement Resistance ◽  
Specific Host ◽  
Host Pathogen ◽  
Resistance Protein

The foodborne pathogen Salmonella is responsible for a wide variety of pathologies depending on the infected host, the infecting serovars, and its set of virulence factors. However, the implication of each of these virulence factors and their role in the specific host-pathogen interplay are not fully understood.

scholarly journals Toxoplasma Effectors Targeting Host Signaling and Transcription

2017 ◽  
Vol 30 (3) ◽  
pp. 615-645 ◽  
Author(s):  
Mohamed-Ali Hakimi ◽  
Philipp Olias ◽  
L. David Sibley
Keyword(s):  
Host Cells ◽  
Content Type ◽  
Apicomplexan Parasites ◽  
Small Noncoding Rnas ◽  
Dense Granules ◽  
Host Pathogen Interaction ◽  
Morphological Studies ◽  
Specific Host ◽  
Host Pathogen ◽  
Host Signaling

SUMMARY Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions. In parallel, studies on host-pathogen interactions identified many host signaling pathways that were mysteriously altered by infection. It was only with the advent of forward and reverse genetic strategies that the connections between individual parasite effectors and the specific host pathways that they targeted finally became clear. The current repertoire of parasite effectors includes ROP kinases and pseudokinases that are secreted during invasion and that block host immune pathways. Similarly, many secretory GRA proteins alter host gene expression by activating host transcription factors, through modification of chromatin, or by inducing small noncoding RNAs. These effectors highlight novel mechanisms by which T. gondii has learned to harness host signaling to favor intracellular survival and will guide future studies designed to uncover the additional complexity of this intricate host-pathogen interaction.

scholarly journals Draft Genomic Sequence of Escherichia coli Sequence Type 131, Isolated from Retail Chicken Skin

2019 ◽  
Vol 8 (7) ◽  
Author(s):  
Aixia Xu ◽  
William Mackay ◽  
O. Joseph Scullen ◽  
Shiowshuh Sheen ◽  
Rommel Ramos ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Urinary Tract ◽  
Virulence Factors ◽  
Genomic Sequence ◽  
Foodborne Pathogen ◽  
Sequence Type ◽  
Content Type ◽  
Chicken Skin ◽  
Tract Infections

Escherichia coli sequence type 131 (ST131) is a foodborne pathogen increasingly associated with urinary tract infections. We report here the draft genomic sequence of ST131 B7S75, isolated from retail chicken skin, including information about its virulence factors and antibiotic resistance.

scholarly journals Host-Pathogen Interactions in Gram-Positive Bacterial Pneumonia

2019 ◽  
Vol 32 (3) ◽  
Author(s):  
Jennifer A. Grousd ◽  
Helen E. Rich ◽  
John F. Alcorn
Keyword(s):  
Virulence Factors ◽  
Secondary Infection ◽  
Community Acquired Pneumonia ◽  
Inflammasome Activation ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
Host Immune Responses ◽  
Pathogen Virulence ◽  
Host Cell Death ◽  
Host Pathogen

SUMMARY Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Despite broad literature including basic and translational scientific studies, many gaps in our understanding of host-pathogen interactions remain. In this review, pathogen virulence factors that drive lung infection and injury are discussed in relation to their associated host immune pathways. CAP epidemiology is considered, with a focus on Staphylococcus aureus and Streptococcus pneumoniae as primary pathogens. Bacterial factors involved in nasal colonization and subsequent virulence are illuminated. A particular emphasis is placed on bacterial pore-forming toxins, host cell death, and inflammasome activation. Identified host-pathogen interactions are then examined by linking pathogen factors to aberrant host response pathways in the context of acute lung injury in both primary and secondary infection. While much is known regarding bacterial virulence and host immune responses, CAP management is still limited to mostly supportive care. It is likely that improvements in therapy will be derived from combinatorial targeting of both pathogen virulence factors and host immunomodulation.

scholarly journals IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction

2014 ◽  
Vol 83 (2) ◽  
pp. 492-501 ◽  
Author(s):  
Jasper Swierstra ◽  
Stephanie Debets ◽  
Corné de Vogel ◽  
Nicole Lemmens-den Toom ◽  
Nelianne Verkaik ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Geographical Location ◽  
Antibody Responses ◽  
Inhibitory Protein ◽  
Content Type ◽  
Immune Modulators ◽  
Host Interactions ◽  
Host Pathogen ◽  
Toxic Shock Syndrome Toxin

IgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses againstStaphylococcus aureusmight generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 differentS. aureusvirulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries. IgGt responses were detected against all tested antigens. These were mostly IgG1 responses. In contrast, IgG4 antibodies were detected to alpha-toxin, chemotaxis inhibitory protein ofS. aureus(CHIPS), exfoliative toxins A and B (ETA and -B), HlgB, IsdA, LukD, -E, -F, and -S, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin C (SEC), staphylococcal superantigen-like proteins 1, 3, 5, and 9 (SSL1, -3, -5, and -9), and toxic shock syndrome toxin 1 (TSST-1) only. Large interpatient variability was observed, and the type of infection or geographical location did not reveal conserved patterns of response. As persistentS. aureuscarriers trended toward IgG4 responses to a larger number of antigens than persistent noncarriers, we also investigated sera from patients with epidermolysis bullosa (EB), a genetic blistering disease associated with highS. aureuscarriage rates. EB patients responded immunologically to significantly more antigens than noncarriers and trended toward even more responses than carriers. Altogether, we conclude that the IgG4 responses against a restricted panel of staphylococcal antigens consisting primarily of immune modulators and particular toxins indicate important roles for these virulence factors in staphylococcal pathogen-host interactions, such as chronicity of colonization and/or (subclinical) infections.

scholarly journals Nutritional Regulation of the Sae Two-Component System by CodY inStaphylococcus aureus

2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Kevin D. Mlynek ◽  
William E. Sause ◽  
Derek E. Moormeier ◽  
Marat R. Sadykov ◽  
Kurt R. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Factors ◽  
Virulence Gene ◽  
Nutrient Depletion ◽  
Global Regulator ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Two Component

ABSTRACTStaphylococcus aureussubverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via theS. aureusexoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of thesaeP1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY repressessaeexpression by blocking SaeR binding. Epistasis experiments support a model that CodY also controlssaeindirectly through Agr and Rot-mediated repression of thesaeP1 promoter. We also demonstrate that CodY repression ofsaerestrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression.IMPORTANCEBacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens likeS. aureusproduce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by whichS. aureusdelays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

scholarly journals A Cronobacter turicensis O1 Antigen-Specific Monoclonal Antibody Inhibits Bacterial Motility and Entry into Epithelial Cells

2014 ◽  
Vol 83 (3) ◽  
pp. 876-887 ◽  
Author(s):  
Kristina Schauer ◽  
Angelika Lehner ◽  
Richard Dietrich ◽  
Ina Kleinsteuber ◽  
Rocío Canals ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Epithelial Cells ◽  
Foodborne Pathogen ◽  
Antimicrobial Effect ◽  
Infection Model ◽  
Cell Agglutination ◽  
Content Type ◽  
O Antigen ◽  
Lethal Infection ◽  
Insight Into

Cronobacter turicensisis an opportunistic foodborne pathogen that can cause a rare but sometimes lethal infection in neonates. Little is known about the virulence mechanisms and intracellular lifestyle of this pathogen. In this study, we developed an IgG monoclonal antibody (MAb; MAb 2G4) that specifically recognizes the O1 antigen ofC. turicensiscells. The antilipopolysaccharide antibody bound predominantly monovalently to the O antigen and reduced bacterial growth without causing cell agglutination. Furthermore, binding of the antibody to the O1 antigen ofC. turicensiscells caused a significant reduction of the membrane potential which is required to energize flagellar rotation, accompanied by a decreased flagellum-based motility. These results indicate that binding of IgG to the O antigen ofC. turicensiscauses a direct antimicrobial effect. In addition, this feature of the antibody enabled new insight into the pathogenicity ofC. turicensis. In a tissue culture infection model, pretreatment ofC. turicensiswith MAb 2G4 showed no difference in adhesion to human epithelial cells, whereas invasion of bacteria into Caco-2 cells was significantly inhibited.

scholarly journals Low-Molecular-Weight Metabolites Secreted by Paenibacillus larvae as Potential Virulence Factors of American Foulbrood

2014 ◽  
Vol 80 (8) ◽  
pp. 2484-2492 ◽  
Author(s):  
Hedwig-Annabell Schild ◽  
Sebastian W. Fuchs ◽  
Helge B. Bode ◽  
Bernd Grünewald
Keyword(s):  
Molecular Weight ◽  
Virulence Factors ◽  
Gene Clusters ◽  
Paenibacillus Larvae ◽  
Economic Losses ◽  
Low Molecular Weight ◽  
American Foulbrood ◽  
Toxic Activity ◽  
Content Type

ABSTRACTThe spore-forming bacteriumPaenibacillus larvaecauses a severe and highly infective bee disease, American foulbrood (AFB). Despite the large economic losses induced by AFB, the virulence factors produced byP. larvaeare as yet unknown. To identify such virulence factors, we experimentally infected young, susceptible larvae of the honeybee,Apis mellifera carnica, with differentP. larvaeisolates. Honeybee larvae were rearedin vitroin 24-well plates in the laboratory after isolation from the brood comb. We identified genotype-specific differences in the etiopathology of AFB between the tested isolates ofP. larvae, which were revealed by differences in the median lethal times. Furthermore, we confirmed that extracts ofP. larvaecultures contain low-molecular-weight compounds, which are toxic to honeybee larvae. Our data indicate thatP. larvaesecretes metabolites into the medium with a potent honeybee toxic activity pointing to a novel pathogenic factor(s) ofP. larvae. Genome mining ofP. larvaesubsp.larvaeBRL-230010 led to the identification of several biosynthesis gene clusters putatively involved in natural product biosynthesis, highlighting the potential ofP. larvaeto produce such compounds.

scholarly journals Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and ReducesIn VivoPathogenicity

2012 ◽  
Vol 57 (1) ◽  
pp. 445-451 ◽  
Author(s):  
Ilka Tiemy Kato ◽  
Renato Araujo Prates ◽  
Caetano Padial Sabino ◽  
Beth Burgwyn Fuchs ◽  
George P. Tegos ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Sodium Dodecyl ◽  
Systemic Infection ◽  
Tube Formation ◽  
Photodynamic Inactivation ◽  
Content Type ◽  
Daughter Cells

ABSTRACTThe objective of this study was to evaluate whetherCandida albicansexhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells.C. albicanswas exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (λ 660 nm, 75 mW/cm2, 9 to 27 J/cm2).In vitro, we evaluated APDI effects onC. albicansgrowth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility.In vivo, we evaluatedC. albicanspathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability ofC. albicansto form germ tubes compared to untreated cells (P< 0.05). Survival of mice systemically infected withC. albicanspretreated with APDI was significantly increased compared to mice infected with untreated yeast (P< 0.05). APDI increasedC. albicanssensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole forC. albicanswas also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells ofC. albicanssubmitted to APDI. These data suggest that APDI may inhibit virulence factors and reducein vivopathogenicity ofC. albicans. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treatC. albicansinfections.

scholarly journals New Aspects of RpoE in Uropathogenic Proteus mirabilis

2014 ◽  
Vol 83 (3) ◽  
pp. 966-977 ◽  
Author(s):  
Ming-Che Liu ◽  
Kuan-Ting Kuo ◽  
Hsiung-Fei Chien ◽  
Yi-Lin Tsai ◽  
Shwu-Jen Liaw
Keyword(s):  
Urinary Tract ◽  
Virulence Factors ◽  
Stress Responses ◽  
Proteus Mirabilis ◽  
Immune Cell ◽  
Polymyxin B ◽  
Urothelial Cells ◽  
Cationic Antimicrobial Peptide ◽  
Content Type ◽  
Tract Infections

Proteus mirabilisis a common human pathogen causing recurrent or persistent urinary tract infections (UTIs). The underlying mechanisms forP. mirabilisto establish UTIs are not fully elucidated. In this study, we showed that loss of the sigma factor E (RpoE), mediating extracytoplasmic stress responses, decreased fimbria expression, survival in macrophages, cell invasion, and colonization in mice but increased the interleukin-8 (IL-8) expression of urothelial cells and swarming motility. This is the first study to demonstrate that RpoE modulated expression of MR/P fimbriae by regulatingmrpI, a gene encoding a recombinase controlling the orientation of MR/P fimbria promoter. By real-time reverse transcription-PCR, we found that the IL-8 mRNA amount of urothelial cells was induced significantly by lipopolysaccharides extracted fromrpoEmutant but not from the wild type. These RpoE-associated virulence factors should be coordinately expressed to enhance the fitness ofP. mirabilisin the host, including the avoidance of immune attacks. Accordingly,rpoEmutant-infected mice displayed more immune cell infiltration in bladders and kidneys during early stages of infection, and therpoEmutant had a dramatically impaired ability of colonization. Moreover, it is noteworthy that urea (the major component in urine) and polymyxin B (a cationic antimicrobial peptide) can induce expression ofrpoEby the reporter assay, suggesting that RpoE might be activated in the urinary tract. Altogether, our results indicate that RpoE is important in sensing environmental cues of the urinary tract and subsequently triggering the expression of virulence factors, which are associated with the fitness ofP. mirabilis, to build up a UTI.

scholarly journals A Novel Line Immunoassay Based on Recombinant Virulence Factors Enables Highly Specific and Sensitive Serologic Diagnosis of Helicobacter pylori Infection

2013 ◽  
Vol 20 (11) ◽  
pp. 1703-1710 ◽  
Author(s):  
Luca Formichella ◽  
Laura Romberg ◽  
Christian Bolz ◽  
Michael Vieth ◽  
Michael Geppert ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Immune Responses ◽  
Virulence Factors ◽  
Gastrointestinal Disease ◽  
Individual Risk ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Serologic Test ◽  
Content Type ◽  
H Pylori

ABSTRACTHelicobacter pyloricolonizes half of the world's population, and infection can lead to ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Serology is the only test applicable for large-scale, population-based screening, but current tests are hampered by a lack of sensitivity and/or specificity. Also, no serologic test allows the differentiation of type I and type II strains, which is important for predicting the clinical outcome.H. pylorivirulence factors have been associated with disease, but direct assessment of virulence factors requires invasive methods to obtain gastric biopsy specimens. Our work aimed at the development of a highly sensitive and specific, noninvasive serologic test to detect immune responses to importantH. pylorivirulence factors. This line immunoassay system (recomLine) is based on recombinant proteins. For this assay, six highly immunogenic virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) were expressed inEscherichia coli, purified, and immobilized to nitrocellulose membranes to detect serological immune responses in patient's sera. For the validation of the line assay, a cohort of 500 patients was screened, of which 290 (58.0%) wereH. pylorinegative and 210 (42.0%) were positive by histology. The assay showed sensitivity and specificity of 97.6% and 96.2%, respectively, compared to histology. In direct comparison to lysate blotting and enzyme-linked immunosorbent assay (ELISA), therecomLine assay had increased discriminatory power. For the assessment of individual risk for gastrointestinal disease, the test must be validated in a larger and defined patient cohort. Taking the data together, therecomLine assay provides a valuable tool for the diagnosis ofH. pyloriinfection.

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