Bioengineering of LAB vector expressing Haemolysin co-regulated protein (Hcp): a strategic approach to control gut colonization of Campylobacter jejuni in a murine model

Abstract Background Campylobacter jejuni (C. jejuni) is accountable for more than 400 million cases of gastroenteritis each year and is listed as a high-priority gut pathogen by the World Health Organization (WHO). Although the acute infection of C. jejuni (campylobacteriosis) is commonly treated with macrolides and fluoroquinolones, the emergence of antibiotic resistance among C. jejuni warrants the need for an alternative approach to control campylobacteriosis in humans. To this end, vaccines remain a safe, effective, and widely accepted strategy for controlling emerging and re-emerging infectious diseases. In search of a suitable vaccine against campylobacteriosis, recently, we demonstrated the potential of recombinant Haemolysin co-regulated protein (Hcp) of C. jejuni Type VI secretion system (T6SS) in imparting significant immune-protection against cecal colonization of C. jejuni; however, in the avian model. Since clinical features of human campylobacteriosis are more complicated than the avians, we explored the potential of Hcp as a T6SS targeted vaccine in a murine model as a more reliable and reproducible experimental host to study vaccine-induced immune-protection against C. jejuni. Because C. jejuni primarily utilizes the mucosal route for host pathogenesis, we analyzed the immunogenicity of a mucosally deliverable bioengineered Lactic acid bacteria (LAB), Lactococcus lactis (L. lactis), expressing Hcp. Considering the role of Hcp in both structural (membrane-bound) and functional (effector protein) exhibition of C. jejuni T6SS, a head-to-head comparison of two different forms of recombinant LAB vectors (cell wall anchored and secreted form of Hcp) were tested and assessed for the immune phenotypes of each modality in BALB/c mice. Results We show that regardless of the Hcp protein localization, mucosal delivery of bioengineered LAB vector expressing Hcp induced high-level production of antigen-specific neutralizing antibody (sIgA) in the gut with the potential to reduce the cecal load of C. jejuni in mice. Conclusion Together with the non-commensal nature of L. lactis, short gut transit time in humans, and the ability to express the heterologous protein in the gut, the present study highlights the benefits of bioengineered LAB vectors based mucosal vaccine modality against C. jejuni without the risk of immunotolerance.

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The Interplay between Campylobacter and the Caecal Microbial Community of Commercial Broiler Chickens over Time

Microorganisms ◽

10.3390/microorganisms9020221 ◽

2021 ◽

Vol 9 (2) ◽

pp. 221

Author(s):

Ilaria Patuzzi ◽

Massimiliano Orsini ◽

Veronica Cibin ◽

Sara Petrin ◽

Eleonora Mastrorilli ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Broiler Chickens ◽

Control Strategies ◽

Chicken Meat ◽

Control Measures ◽

Microbial Network ◽

Gut Colonization ◽

Commercial Broiler ◽

Zoonotic Bacteria ◽

Human Infections

Campylobacter is the most frequent foodborne zoonotic bacteria worldwide, with chicken meat being overwhelmingly the most important reservoir for human infections. Control measures implemented at the farm level (i.e., biosecurity or vaccination), which have been successfully applied to limit other pathogens, such as Salmonella, have not been effective in reducing Campylobacter occurrence. Thus, new approaches are needed to fully understand the ecological interactions of Campylobacter with host animals to effectively comprehend its epidemiology. The objective of this study was to analyse longitudinally the gut microbiota composition of Campylobacter-infected and non-infected farms to identify any difference that could potentially be indicative of gut colonization by Campylobacter spp. Differences in the colonization rate and timing were observed at the farms that became positive for Campylobacter jejuni over the investigated time points, even though in positive tests, the occurrence of Campylobacter jejuni gut colonization was not observed before the second week of the life of the birds. Significant differences were observed in the abundances of specific bacterial taxa between the microbiota of individuals belonging to farms that became Campylobacter positive during the study and those who remained negative with particular reference to Bacteroidales and Clostridiales, respectively. Moreover, Campylobacter colonization dramatically influenced the microbiota richness, although to a different extent depending on the infection timing. Finally, a key role of Faecalibacterium and Lactobacillus genera on the Campylobacter microbial network was observed. Understanding the ecology of the Campylobacter interaction with host microbiota during infection could support novel approaches for broiler microbial barrier restoration. Therefore, evidence obtained through this study can be used to identify options to reduce the incidence of infection at a primary production level based on the targeted influence of the intestinal microbiota, thus helping develop new control strategies in order to mitigate the risk of human exposure to Campylobacter by chicken meat consumption.

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ICSBP-mediated immune protection against BCR-ABL–induced leukemia requires the CCL6 and CCL9 chemokines

Blood ◽

10.1182/blood-2008-07-167189 ◽

2009 ◽

Vol 113 (16) ◽

pp. 3813-3820 ◽

Cited By ~ 15

Author(s):

Valentina Nardi ◽

Olaia Naveiras ◽

Mohammad Azam ◽

George Q. Daley

Keyword(s):

Murine Model ◽

Consensus Sequence ◽

Myelogenous Leukemia ◽

Transformed Cells ◽

Type I ◽

Immune Protection ◽

Immune Mechanism ◽

Type I Ifns ◽

New Strategies

Abstract Interferon (IFN) is effective at inducing complete remissions in patients with chronic myelogenous leukemia (CML), and evidence supports an immune mechanism. Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL–transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of BCR-ABL–induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the type I IFNs and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression. Insights into the role of these chemokines in the antileukemic response of IFNs suggest new strategies for immunotherapy of CML.

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Live wildlife trade in markets - a scoping review to inform risk assessment of emerging infectious diseases

10.1101/2021.09.13.21263377 ◽

2021 ◽

Author(s):

Victoria J Brookes ◽

Okta Wismandanu ◽

Etih Sudarnika ◽

Justin A Roby ◽

Lynne Hayes ◽

...

Keyword(s):

Risk Assessment ◽

Infectious Diseases ◽

Scoping Review ◽

Epistemic Uncertainty ◽

Mammalian Species ◽

Emerging Infectious Diseases ◽

World Health Organisation ◽

World Health ◽

Wildlife Trade ◽

The Impact

Wet markets are important for food security in many regions worldwide but have come under scrutiny due to their potential role in the emergence of infectious diseases. The sale of live wildlife has been highlighted as a particular risk, and the World Health Organisation has called for the banning of live, wild-caught mammalian species in markets unless risk assessment and effective regulations are in place. Following PRISMA guidelines, we conducted a global scoping review of peer-reviewed information about the sale of live, terrestrial wildlife in markets that are likely to sell fresh food, and collated data about the characteristics of such markets, activities involving live wildlife, the species sold, their purpose, and animal, human, and environmental health risks that were identified. Of the 59 peer-reviewed records within scope, only 25% (n = 14) focussed on disease risks; the rest focused on the impact of wildlife sale on conservation. Although there were some global patterns (for example, the types of markets and purpose of sale of wildlife), there was wide diversity and huge epistemic uncertainty in all aspects associated with live, terrestrial wildlife sale in markets such that the feasibility of accurate assessment of the risk of emerging infectious disease associated with live wildlife trade in markets is limited. Given the value of both wet markets and wildlife trade and the need to support food affordability and accessibility, conservation, public health, and the social and economic aspects of livelihoods of often vulnerable people, there are major information gaps that need to be addressed to develop evidence-based policy in this environment. This review identifies these gaps and provides a foundation from which information for risk assessments can be collected.

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Bioinformatic Analysis of the Campylobacter jejuni Type VI Secretion System and Effector Prediction

Frontiers in Microbiology ◽

10.3389/fmicb.2021.694824 ◽

2021 ◽

Vol 12 ◽

Author(s):

Luca Robinson ◽

Janie Liaw ◽

Zahra Omole ◽

Dong Xia ◽

Arnoud H. M. van Vliet ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Variable Region ◽

Pathogenicity Island ◽

Bioinformatic Analysis ◽

Secretion System ◽

Open Reading Frames ◽

Host Cells ◽

Type Vi Secretion System ◽

Bacterial Antagonism ◽

Type Vi Secretion

The Type VI Secretion System (T6SS) has important roles relating to bacterial antagonism, subversion of host cells, and niche colonisation. Campylobacter jejuni is one of the leading bacterial causes of human gastroenteritis worldwide and is a commensal coloniser of birds. Although recently discovered, the T6SS biological functions and identities of its effectors are still poorly defined in C. jejuni. Here, we perform a comprehensive bioinformatic analysis of the C. jejuni T6SS by investigating the prevalence and genetic architecture of the T6SS in 513 publicly available genomes using C. jejuni 488 strain as reference. A unique and conserved T6SS cluster associated with the Campylobacter jejuni Integrated Element 3 (CJIE3) was identified in the genomes of 117 strains. Analyses of the T6SS-positive 488 strain against the T6SS-negative C. jejuni RM1221 strain and the T6SS-positive plasmid pCJDM202 carried by C. jejuni WP2-202 strain defined the “T6SS-containing CJIE3” as a pathogenicity island, thus renamed as Campylobacter jejuni Pathogenicity Island-1 (CJPI-1). Analysis of CJPI-1 revealed two canonical VgrG homologues, CJ488_0978 and CJ488_0998, harbouring distinct C-termini in a genetically variable region downstream of the T6SS operon. CJPI-1 was also found to carry a putative DinJ-YafQ Type II toxin-antitoxin (TA) module, conserved across pCJDM202 and the genomic island CJIE3, as well as several open reading frames functionally predicted to encode for nucleases, lipases, and peptidoglycan hydrolases. This comprehensive in silico study provides a framework for experimental characterisation of T6SS-related effectors and TA modules in C. jejuni.

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Emerging zoonoses in Indonesia: implication for the future

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2020.v39.151-152 ◽

2020 ◽

Vol 39 (3) ◽

pp. 151

Author(s):

Toni Wandra

Keyword(s):

Infectious Diseases ◽

World Health Organization ◽

Emerging Infectious Diseases ◽

Zoonotic Diseases ◽

World Health ◽

Emerging Zoonoses ◽

The Future ◽

Health Organization

World Health Organization (WHO) defines zoonotic diseases (zoonoses) as those diseases and infections which are naturally transmitted between vertebrate animals and humans. More than 250 zoonoses have been described, over 60% of pathogens that cause diseases in humans are zoonoses of animals, and 75% of emerging infectious diseases. Most pandemics are caused by zoonoses.

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The role of nutrition in strengthening immune system against newly emerging viral diseases: case of SARS-CoV-2

The North African Journal of Food and Nutrition Research - July-December 2021 ◽

10.51745/najfnr.4.7.240-244 ◽

2020 ◽

Vol 4 (7) ◽

pp. 240-244

Author(s):

Meghit Boumediene Khaled ◽

Nada Benajiba

Keyword(s):

Immune System ◽

Infectious Diseases ◽

Nutritional Status ◽

Infected Individual ◽

Emerging Infectious Diseases ◽

The Body ◽

Healthy Diet ◽

World Health ◽

Viral Diseases ◽

Prevention Measures

The immune system is involved in the protection of host against environmental agents such as pathogenic micro-organisms (bacteria, fungi, and viruses) and chemicals, thereby preserving the integrity of the body. To preserve organism defense mechanisms, adequate nutritional status should be maintained with appropriate intakes of calories, vitamins, minerals and water that should be continuously provided by a healthy diet. The emergence of new infectious diseases with new pathogenic properties constitutes a serious health issue worldwide. Severe acute respiratory syndrome (SARS) represents one of the most recent emerging infectious diseases, caused by a novel coronavirus member called (SARS-CoV-2), identified in Wuhan, Hubei, China in December 2019, and recognized as pandemic by the World Health Organization (WHO). The nutritional status of each COVID-19-infected patient should be assessed prior undertaking treatments. Nutritional support should be the basis of management of any infected individual. However, prevention measures remain the first priority and strategy to develop throughout proper hygiene, healthy diet and staying home. Keywords: Nutrition, Immune system, Viral diseases, SARS-CoV-2.

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Complete Genome Sequence and Annotation of Campylobacter jejuni YH003, Isolated from Retail Chicken

Microbiology Resource Announcements ◽

10.1128/mra.01307-19 ◽

2020 ◽

Vol 9 (4) ◽

Author(s):

Yiping He ◽

Sue Reed ◽

Terence P. Strobaugh

Keyword(s):

Campylobacter Jejuni ◽

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Type Vi Secretion System ◽

Multidrug Efflux ◽

Content Type ◽

Resistance Factors ◽

Genes Encoding ◽

Multidrug Efflux System

The complete genome sequence of Campylobacter jejuni YH003, isolated from retail chicken, was determined using PacBio and Illumina technologies. The assembled genome is 1,743,985 bp (G+C content of 30.3%). Genome annotation revealed several genes encoding virulence and antibiotic resistance factors, including a type VI secretion system, cytolethal distending toxins, and a multidrug efflux system.

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