scholarly journals Campylobacter jejuni Virulence Factors Identified by Modulating Their Synthesis on Ribosomes With Altered rRNA Methylation

2022 ◽  
Vol 11 ◽  
Author(s):  
Agnieszka Sałamaszyńska-Guz ◽  
Pernille Kronholm Rasmussen ◽  
Małgorzata Murawska ◽  
Stephen Douthwaite
Keyword(s):  
Campylobacter Jejuni ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Membrane Vesicle ◽  
Food Poisoning ◽  
Host Cells ◽  
23S Rrna ◽  
The Usa ◽  
Human Campylobacteriosis ◽  
Infective Agent

Campylobacter jejuni is a major cause of food poisoning worldwide, and remains the main infective agent in gastroenteritis and related intestinal disorders in Europe and the USA. As with all bacterial infections, the stages of adhesion to host tissue, survival in the host and eliciting disease all require the synthesis of proteinaceous virulence factors on the ribosomes of the pathogen. Here, we describe how C. jejuni virulence is attenuated by altering the methylation of its ribosomes to disrupt the composition of its proteome, and how this in turn provides a means of identifying factors that are essential for infection and pathogenesis. Specifically, inactivation of the C. jejuni Cj0588/TlyA methyltransferase prevents methylation of nucleotide C1920 in the 23S rRNA of its ribosomes and reduces the pathogen’s ability to form biofilms, to attach, invade and survive in host cells, and to provoke the innate immune response. Mass spectrometric analyses of C. jejuni TlyA-minus strains revealed an array of subtle changes in the proteome composition. These included reduced amounts of the cytolethal distending toxin (CdtC) and the MlaEFD proteins connected with outer membrane vesicle (OMV) production. Inactivation of the cdtC and mlaEFD genes confirmed the importance of their encoded proteins in establishing infection. Collectively, the data identify a subset of genes required for the onset of human campylobacteriosis, and serve as a proof of principle for use of this approach in detecting proteins involved in bacterial pathogenesis.

scholarly journals Virulence and Antimicrobial Resistance inCampylobacterspp. from a Peruvian Pediatric Cohort

Scientifica ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Angela Lluque ◽  
Maribel Riveros ◽  
Ana Prada ◽  
Theresa J. Ochoa ◽  
Joaquim Ruiz
Keyword(s):  
Cohort Study ◽  
Antimicrobial Resistance ◽  
Nalidixic Acid ◽  
Campylobacter Jejuni ◽  
Virulence Factors ◽  
Antimicrobial Agents ◽  
23S Rrna ◽  
Campylobacter Coli ◽  
Ciprofloxacin Resistance ◽  
Almost All

The presence of virulence factors (VFs) and mechanisms of quinolones and macrolide resistance was analyzed inCampylobacterspp. from a pediatric cohort study in Lima. In 149 isolates (39Campylobacter jejuniand 24Campylobacter colifrom diarrheic cases; 57C. jejuniand 29C. colifrom controls), the presence of thecdtABCandcadFgenes andiammarker was established. Nalidixic acid, ciprofloxacin, erythromycin, and azithromycin susceptibilities were established in 115 isolates and tetracycline-susceptibility was established in 100 isolates. The presence of mutations in thegyrA,parC,and23S rRNAgenes was determined. ThecadFgene and all genes from thecdtABCoperon were significantly more frequent amongC. jejuni(P<0.0001); theiammarker was more frequent inC. coli(P<0.0001). No differences were observed in VFs between cases and controls. Almost all isolates were tetracycline-resistant; nalidixic acid and ciprofloxacin resistance reached levels of 90.4% and 88.7%, respectively. Resistance to macrolides was 13% (C. jejuni4.3%;C. coli26.1%). Resistance to ciprofloxacin was related to GyrA Thr86 substitutions, while 13 of 15 macrolide-resistant isolates possessed a23S rRNAmutation (A2075G). Differences in the presence of VFs and alarming levels of resistance to tested antimicrobial agents were observed amongC. jejuniandC. coli.

scholarly journals Methionine Sulfoxide Reductase Enzymes: A Possible Virulence Factor for the Management of Antibiotic Resistance Crisis in the Climate Change Era

2019 ◽  
pp. 443-446
Author(s):  
Cesare Achilli ◽  
Annarita Ciana ◽  
Giampaolo Minetti
Keyword(s):  
Antibiotic Resistance ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Host Cells ◽  
Public Health Issue ◽  
Resistant Bacteria ◽  
Rapid Progression ◽  
Drug Resistant

The problem of antibiotic resistance develops when bacteria are able to grow in the presence of conventional antimicrobial drugs and today represents a serious public health issue. The environmental effects of global warming, by unknown genomic mechanisms of adaption, could dramatically increase this phenomenon and support a more rapid progression to “post-antibiotic era”, in which common infections will be untreatable. Alternative approaches toward drug-resistant bacterial infections need to be explored to ensure effective therapies. Bacterial pathogens produce virulence factors that allow them to invade and to damage host cells. Methionine sulfoxide reductase (Msr) enzymes (MsrAs and MsrBs) are important, but poor studied, virulence factors for many bacterial strains. A deeper insight into their mechanism of action and regulation could help in developing novel therapeutic strategies toward drug-resistant bacteria, in order to overcome the antibiotic resistance crisis.

Influence of mutation in cj0183 and cj0588 genes for colonization abilities of Campylobacter jejuni in Caco-2 cells using confocal laser scanning microscope

2013 ◽  
Vol 16 (2) ◽  
pp. 387-389
Author(s):  
A. Sałamaszyńska-Guz ◽  
M.M. Godlewski ◽  
D. Klimuszko
Keyword(s):  
Cell Line ◽  
Campylobacter Jejuni ◽  
Virulence Factors ◽  
Laser Scanning ◽  
Confocal Laser Scanning Microscope ◽  
Host Cells ◽  
Confocal Laser ◽  
Single Mutation ◽  
Scanning Microscope ◽  
Invasion Index

AbstractThe cj0183 and cj0588 genes identified in the Campylobacter jejuni NCTC 11168 genome encode proteins with homology to virulence factors found in other bacteria. Previous studies showed that single mutation in the cj0183 gene does not affect adhesion of C. jejuni to the Caco-2 cell line whereas protein encoded by cj0588 is involved in adherence to the Caco-2 cells. In the presented study differences in invasion index were observed between mutants in both genes and single mutation of cj0588 in 81116 and 81-176 C. jejuni strains. This fact indicates that Cj0183 protein might play some role in invasion of bacteria into host cells.

scholarly journals Campylobacter jejuni Outer Membrane Vesicles Play an Important Role in Bacterial Interactions with Human Intestinal Epithelial Cells

2012 ◽  
Vol 80 (12) ◽  
pp. 4089-4098 ◽  
Author(s):  
Abdi Elmi ◽  
Eleanor Watson ◽  
Pamela Sandu ◽  
Ozan Gundogdu ◽  
Dominic C. Mills ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Campylobacter Jejuni ◽  
Virulence Factors ◽  
Intestinal Epithelial Cells ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Intestinal Epithelial ◽  
Secretion Systems ◽  
Content Type

ABSTRACTCampylobacter jejuniis the most prevalent cause of food-borne gastroenteritis in the developed world; however, the molecular basis of pathogenesis is unclear. Secretion of virulence factors is a key mechanism by which enteric bacterial pathogens interact with host cells to enhance survival and/or damage the host. However,C. jejunilacks the virulence-associated secretion systems possessed by other enteric pathogens. Many bacterial pathogens utilize outer membrane vesicles (OMVs) for delivery of virulence factors into host cells. In the absence of prototypical virulence-associated secretion systems, OMVs could be an important alternative for the coordinated delivery ofC. jejuniproteins into host cells. Proteomic analysis ofC. jejuni11168H OMVs identified 151 proteins, including periplasmic and outer membrane-associated proteins, but also many determinants known to be important in survival and pathogenesis, including the cytolethal distending toxin (CDT).C. jejuniOMVs contained 16N-linked glycoproteins, indicating a delivery mechanism by which these periplasm-located yet immunogenic glycoproteins can interact with host cells.C. jejuniOMVs possess cytotoxic activity and induce a host immune response from T84 intestinal epithelial cells (IECs), which was not reduced by OMV pretreatment with proteinase K or polymyxin B prior to coincubation with IECs. Pretreatment of IECs with methyl-beta-cyclodextrin partially blocks OMV-induced host immune responses, indicating a role for lipid rafts in host cell plasma membranes during interactions withC. jejuniOMVs. OMVs isolated from aC. jejuni11168HcdtAmutant induced interleukin-8 (IL-8) to the same extent as did wild-type OMVs, suggesting OMV induction of IL-8 is independent of CDT.

scholarly journals Impaired Fitness and Transmission of Macrolide-Resistant Campylobacter jejuni in Its Natural Host

2011 ◽  
Vol 56 (3) ◽  
pp. 1300-1308 ◽  
Author(s):  
Taradon Luangtongkum ◽  
Zhangqi Shen ◽  
Virginia W. Seng ◽  
Orhan Sahin ◽  
Byeonghwa Jeon ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Natural Host ◽  
Macrolide Resistance ◽  
23S Rrna ◽  
Pathogenic Organism ◽  
Content Type ◽  
Zoonotic Pathogen ◽  
Natural Reservoir ◽  
Antibiotic Selection Pressure ◽  
Human Campylobacteriosis

ABSTRACTCampylobacter jejuniis a major zoonotic pathogen transmitted to humans via the food chain and is prevalent in chickens, a natural reservoir for this pathogenic organism. Due to the importance of macrolide antibiotics in clinical therapy of human campylobacteriosis, development of macrolide resistance inCampylobacterhas become a concern for public health. To facilitate the control of macrolide-resistantCampylobacter, it is necessary to understand if macrolide resistance affects the fitness and transmission ofCampylobacterin its natural host. In this study we conducted pairwise competitions and comingling experiments in chickens using clonally related and isogenicC. jejunistrains, which are either susceptible or resistant to erythromycin (Ery). In every competition pair, Ery-resistant (Eryr)Campylobacterwas consistently outcompeted by the Ery-susceptible (Erys) strain. In the comingling experiments, EryrCampylobacterfailed to transmit to chickens precolonized by ErysCampylobacter, while isogenic ErysCampylobacterwas able to transmit to and establish dominance in chickens precolonized by EryrCampylobacter. The fitness disadvantage was linked to the resistance-conferring mutations in the 23S rRNA. These findings clearly indicate that acquisition of macrolide resistance impairs the fitness and transmission ofCampylobacterin chickens, suggesting that the prevalence of macrolide-resistantC. jejuniwill likely decrease in the absence of antibiotic selection pressure.

scholarly journals The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas M. Negretti ◽  
Christopher R. Gourley ◽  
Prabhat K. Talukdar ◽  
Geremy Clair ◽  
Courtney M. Klappenbach ◽  
...  
Keyword(s):  
Host Cell ◽  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Small Gtpase ◽  
Host Cells ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Cell Binding ◽  
Actin Reorganization ◽  
Cell Cytosol

AbstractCampylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.

scholarly journals Xyloglucan processing machinery in Xanthomonas pathogens and its role in the transcriptional activation of virulence factors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Plinio S. Vieira ◽  
Isabela M. Bonfim ◽  
Evandro A. Araujo ◽  
Ricardo R. Melo ◽  
Augusto R. Lima ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Citrus Canker ◽  
Effector Proteins ◽  
Glycoside Hydrolases ◽  
Host Cells ◽  
System A ◽  
Enzymatic Machinery

AbstractXyloglucans are highly substituted and recalcitrant polysaccharides found in the primary cell walls of vascular plants, acting as a barrier against pathogens. Here, we reveal that the diverse and economically relevant Xanthomonas bacteria are endowed with a xyloglucan depolymerization machinery that is linked to pathogenesis. Using the citrus canker pathogen as a model organism, we show that this system encompasses distinctive glycoside hydrolases, a modular xyloglucan acetylesterase and specific membrane transporters, demonstrating that plant-associated bacteria employ distinct molecular strategies from commensal gut bacteria to cope with xyloglucans. Notably, the sugars released by this system elicit the expression of several key virulence factors, including the type III secretion system, a membrane-embedded apparatus to deliver effector proteins into the host cells. Together, these findings shed light on the molecular mechanisms underpinning the intricate enzymatic machinery of Xanthomonas to depolymerize xyloglucans and uncover a role for this system in signaling pathways driving pathogenesis.

scholarly journals Complement Inactivation Strategy of Staphylococcus aureus Using Decay-Accelerating Factor and the Response of Infected HaCaT Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4015
Author(s):  
Kyoung Ok Jang ◽  
Youn Woo Lee ◽  
Hangeun Kim ◽  
Dae Kyun Chung
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Cells ◽  
Respiratory Infections ◽  
Food Poisoning ◽  
Surface Expression ◽  
Host Cells ◽  
Hacat Cells ◽  
Decay Accelerating Factor ◽  
Ligand Expression ◽  
The Complement System

Staphylococcus aureus is a species of Gram-positive staphylococcus. It can cause sinusitis, respiratory infections, skin infections, and food poisoning. Recently, it was discovered that S. aureus infects epithelial cells, but the interaction between S. aureus and the host is not well known. In this study, we confirmed S. aureus to be internalized by HaCaT cells using the ESAT-6-like protein EsxB and amplified within the host over time by escaping host immunity. S. aureus increases the expression of decay-accelerating factor (CD55) on the surfaces of host cells, which inhibits the activation of the complement system. This mechanism makes it possible for S. aureus to survive in host cells. S. aureus, sufficiently amplified within the host, is released through the initiation of cell death. On the other hand, the infected host cells increase their surface expression of UL16 binding protein 1 to inform immune cells that they are infected and try to be eliminated. These host defense systems seem to involve the alteration of tight junctions and the induction of ligand expression to activate immune cells. Taken together, our study elucidates a novel aspect of the mechanisms of infection and immune system evasion for S. aureus.

scholarly journals Tackling Virulence of Pseudomonas aeruginosa by the Natural Furanone Sotolon

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 871
Author(s):  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Ahmed Al Saqr ◽  
Ahmed Alalaiwe ◽  
Hisham A. Abbas ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Therapeutic Agent ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Resistance Development

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.

scholarly journals Bacteriophage-Based Biosensing of Pseudomonas aeruginosa: An Integrated Approach for the Putative Real-Time Detection of Multi-Drug-Resistant Strains

Biosensors ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 124
Author(s):  
Liliam K. Harada ◽  
Waldemar Bonventi Júnior ◽  
Erica C. Silva ◽  
Thais J. Oliveira ◽  
Fernanda C. Moreli ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Research Effort ◽  
Acquired Resistance ◽  
Integrated Approach ◽  
Healthcare Services ◽  
Host Cells ◽  
Color Changes ◽  
Metabolic Versatility ◽  
The Matrix

During the last decennium, it has become widely accepted that ubiquitous bacterial viruses, or bacteriophages, exert enormous influences on our planet’s biosphere, killing between 4–50% of the daily produced bacteria and constituting the largest genetic diversity pool on our planet. Currently, bacterial infections linked to healthcare services are widespread, which, when associated with the increasing surge of antibiotic-resistant microorganisms, play a major role in patient morbidity and mortality. In this scenario, Pseudomonas aeruginosa alone is responsible for ca. 13–15% of all hospital-acquired infections. The pathogen P. aeruginosa is an opportunistic one, being endowed with metabolic versatility and high (both intrinsic and acquired) resistance to antibiotics. Bacteriophages (or phages) have been recognized as a tool with high potential for the detection of bacterial infections since these metabolically inert entities specifically attach to, and lyse, bacterial host cells, thus, allowing confirmation of the presence of viable cells. In the research effort described herein, three different phages with broad lytic spectrum capable of infecting P. aeruginosa were isolated from environmental sources. The isolated phages were elected on the basis of their ability to form clear and distinctive plaques, which is a hallmark characteristic of virulent phages. Next, their structural and functional stabilization was achieved via entrapment within the matrix of porous alginate, biopolymeric, and bio-reactive, chromogenic hydrogels aiming at their use as sensitive matrices producing both color changes and/or light emissions evolving from a reaction with (released) cytoplasmic moieties, as a bio-detection kit for P. aeruginosa cells. Full physicochemical and biological characterization of the isolated bacteriophages was the subject of a previous research paper.

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