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Transboundary and Emerging Diseases May 2018Porcine pleuropneumonia, caused by the bacterial porcine respiratory tract pathogen Actinobacillus pleuropneumoniae, leads to high economic losses in affected swine... (Review)
Review
Porcine pleuropneumonia, caused by the bacterial porcine respiratory tract pathogen Actinobacillus pleuropneumoniae, leads to high economic losses in affected swine herds in most countries of the world. Pigs affected by peracute and acute disease suffer from severe respiratory distress with high lethality. The agent was first described in 1957 and, since then, knowledge about the pathogen itself, and its interactions with the host, has increased continuously. This is, in part, due to the fact that experimental infections can be studied in the natural host. However, the fact that most commercial pigs are colonized by this pathogen has hampered the applicability of knowledge gained under experimental conditions. In addition, several factors are involved in development of disease, and these have often been studied individually. In a DISCONTOOLS initiative, members from science, industry and clinics exchanged their expertise and empirical observations and identified the major gaps in knowledge. This review sums up published results and expert opinions, within the fields of pathogenesis, epidemiology, transmission, immune response to infection, as well as the main means of prevention, detection and control. The gaps that still remain to be filled are highlighted, and present as well as future challenges in the control of this disease are addressed.
Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Communicable Disease Control; Pleuropneumonia; Swine; Swine Diseases; Zoonoses
PubMed: 29083117
DOI: 10.1111/tbed.12739 -
Immunity Jan 2023There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the...
There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA. Furthermore, in mice without jejunal GATA4 expression, the commensal segmented filamentous bacteria promoted pathogenic inflammatory immune responses that disrupted barrier function and increased mortality upon Citrobacter rodentium infection. In celiac disease patients, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. Taken together, these results reveal broad impacts of GATA4-regulated intestinal regionalization on bacterial colonization and tissue immunity, highlighting an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease.
Topics: Animals; Humans; Mice; Actinobacillus; Enterobacteriaceae Infections; Gastrointestinal Microbiome; GATA4 Transcription Factor; Immunity, Mucosal; Interleukin-17; Intestinal Mucosa; Intestine, Small; Symbiosis
PubMed: 36630917
DOI: 10.1016/j.immuni.2022.12.009 -
Veterinary Research Jun 2020Understudied, coinfections are more frequent in pig farms than single infections. In pigs, the term "Porcine Respiratory Disease Complex" (PRDC) is often used to... (Review)
Review
Understudied, coinfections are more frequent in pig farms than single infections. In pigs, the term "Porcine Respiratory Disease Complex" (PRDC) is often used to describe coinfections involving viruses such as swine Influenza A Virus (swIAV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), and Porcine CircoVirus type 2 (PCV2) as well as bacteria like Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae and Bordetella bronchiseptica. The clinical outcome of the various coinfection or superinfection situations is usually assessed in the studies while in most of cases there is no clear elucidation of the fine mechanisms shaping the complex interactions occurring between microorganisms. In this comprehensive review, we aimed at identifying the studies dealing with coinfections or superinfections in the pig respiratory tract and at presenting the interactions between pathogens and, when possible, the mechanisms controlling them. Coinfections and superinfections involving viruses and bacteria were considered while research articles including protozoan and fungi were excluded. We discuss the main limitations complicating the interpretation of coinfection/superinfection studies, and the high potential perspectives in this fascinating research field, which is expecting to gain more and more interest in the next years for the obvious benefit of animal health.
Topics: Animals; Coinfection; Respiratory Tract Diseases; Superinfection; Sus scrofa; Swine; Swine Diseases
PubMed: 32546263
DOI: 10.1186/s13567-020-00807-8 -
Veterinary Research May 2023Actinobacillus pleuropneumoniae is an important swine respiratory pathogen. Previous studies have suggested that growth as a biofilm is a natural state of A....
Actinobacillus pleuropneumoniae is an important swine respiratory pathogen. Previous studies have suggested that growth as a biofilm is a natural state of A. pleuropneumoniae infection. To understand the survival features involved in the biofilm state, the growth features, morphology and gene expression profiles of planktonic and biofilm A. pleuropneumoniae were compared. A. pleuropneumoniae in biofilms showed reduced viability but maintained the presence of extracellular polymeric substances (EPS) after late log-phase. Under the microscope, bacteria in biofilms formed dense aggregated structures that were connected by abundant EPS, with reduced condensed chromatin. By construction of Δpga and ΔdspB mutants, polymeric β-1,6-linked N-acetylglucosamine and dispersin B were confirmed to be critical for normal biofilm formation. RNA-seq analysis indicated that, compared to their planktonic counterparts, A. pleuropneumoniae in biofilms had an extensively altered transcriptome. Carbohydrate metabolism, energy metabolism and translation were significantly repressed, while fermentation and genes contributing to EPS synthesis and translocation were up-regulated. The regulators Fnr (HlyX) and Fis were found to be up-regulated and their binding motifs were identified in the majority of the differentially expressed genes, suggesting their coordinated global role in regulating biofilm metabolism. By comparing the transcriptome of wild-type biofilm and Δpga, the utilization of oligosaccharides, iron and sulfur and fermentation were found to be important in adhesion and aggregation during biofilm formation. Additionally, when used as inocula, biofilm bacteria showed reduced virulence in mouse, compared with planktonic grown cells. Thus, these results have identified new facets of A. pleuropneumoniae biofilm maintenance and regulation.
Topics: Animals; Swine; Mice; Actinobacillus pleuropneumoniae; Biofilms; Transcriptome; Virulence; Actinobacillus Infections; Swine Diseases
PubMed: 37237397
DOI: 10.1186/s13567-023-01173-x -
Frontiers in Veterinary Science 2023(App) is a globally distributed Gram-negative bacterium that produces porcine pleuropneumonia. This highly contagious disease produces high morbidity and mortality in... (Review)
Review
(App) is a globally distributed Gram-negative bacterium that produces porcine pleuropneumonia. This highly contagious disease produces high morbidity and mortality in the swine industry. However, no effective vaccine exists to prevent it. The infection caused by App provokes characteristic lesions, such as edema, inflammation, hemorrhage, and necrosis, that involve different virulence factors. The colonization and invasion of host surfaces involved structures and proteins such as outer membrane vesicles (OMVs), pili, flagella, adhesins, outer membrane proteins (OMPs), also participates proteases, autotransporters, and lipoproteins. The recent findings on surface structures and proteins described in this review highlight them as potential immunogens for vaccine development.
PubMed: 38098987
DOI: 10.3389/fvets.2023.1276712 -
Toxins Dec 2019The repeats-in-toxin (RTX) family represents a unique class of bacterial exoproteins. The first family members described were toxins from Gram-negative bacterial... (Review)
Review
The repeats-in-toxin (RTX) family represents a unique class of bacterial exoproteins. The first family members described were toxins from Gram-negative bacterial pathogens; however, additional members included exoproteins with diverse functions. Our review focuses on well-characterized RTX family toxins from (LtxA), (LktA), (CyaA), uropathogenic (HlyA), and (ApxIIIA), as well as the studies that have honed in on a single host cell receptor for RTX toxin interactions, the β integrins. The β integrin family is composed of heterodimeric members with four unique alpha subunits and a single beta subunit. β integrins are only found on leukocytes, including neutrophils and monocytes, the first responders to inflammation following bacterial infection. The LtxA, LktA, HlyA, and ApxIIIA toxins target the shared beta subunit, thereby targeting all types of leukocytes. Specific β integrin family domains are required for the RTX toxin's cytotoxic activity and are summarized here. Research examining the domains of the RTX toxins required for cytotoxic and hemolytic activity is also summarized. RTX toxins attack and kill phagocytic immune cells expressing a single integrin family, providing an obvious advantage to the pathogen. The critical question that remains, can the specificity of the RTX-β integrin interaction be therapeutically targeted?
Topics: Animals; Bacterial Proteins; Bacterial Toxins; Cytotoxins; Exotoxins; Host-Pathogen Interactions; Humans; Monocytes; Neutrophils; Protein Domains; Receptors, Cell Surface
PubMed: 31835552
DOI: 10.3390/toxins11120720 -
Frontiers in Veterinary Science 2022
PubMed: 35747238
DOI: 10.3389/fvets.2022.948005 -
Microbiology Spectrum May 2018Members of the highly heterogeneous family cause a wide variety of diseases in humans and animals. Antimicrobial agents are the most powerful tools to control such... (Review)
Review
Members of the highly heterogeneous family cause a wide variety of diseases in humans and animals. Antimicrobial agents are the most powerful tools to control such infections. However, the acquisition of resistance genes, as well as the development of resistance-mediating mutations, significantly reduces the efficacy of the antimicrobial agents. This article gives a brief description of the role of selected members of the family in animal infections and of the most recent data on the susceptibility status of such members. Moreover, a review of the current knowledge of the genetic basis of resistance to antimicrobial agents is included, with particular reference to resistance to tetracyclines, β-lactam antibiotics, aminoglycosides/aminocyclitols, folate pathway inhibitors, macrolides, lincosamides, phenicols, and quinolones. This article focusses on the genera of veterinary importance for which sufficient data on antimicrobial susceptibility and the detection of resistance genes are currently available (, , , , and ). Additionally, the role of plasmids, transposons, and integrative and conjugative elements in the spread of the resistance genes within and beyond the aforementioned genera is highlighted to provide insight into horizontal dissemination, coselection, and persistence of antimicrobial resistance genes. The article discusses the acquisition of diverse resistance genes by the selected members from other Gram-negative or maybe even Gram-positive bacteria. Although the susceptibility status of these members still looks rather favorable, monitoring of their antimicrobial susceptibility is required for early detection of changes in the susceptibility status and the newly acquired/developed resistance mechanisms.
Topics: Animal Diseases; Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Pasteurellaceae; Pasteurellaceae Infections
PubMed: 29916344
DOI: 10.1128/microbiolspec.ARBA-0022-2017 -
Toxins Jul 2016Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus... (Review)
Review
Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus) actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage). Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects.
Topics: Animals; Bacterial Proteins; Bacterial Toxins; Cell Transformation, Neoplastic; DNA Damage; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Host-Pathogen Interactions; Humans; Inflammation; Inflammation Mediators; Neoplasms; Risk Factors
PubMed: 27429000
DOI: 10.3390/toxins8070220 -
Microbiology Spectrum Feb 2022Actinobacillus pleuropneumoniae causes porcine pleuropneumonia, an important disease in the pig industry. Accurate and sensitive diagnostics such as DNA-based...
Actinobacillus pleuropneumoniae causes porcine pleuropneumonia, an important disease in the pig industry. Accurate and sensitive diagnostics such as DNA-based diagnostics are essential for preventing or responding to an outbreak. The specificity of DNA-based diagnostics depends on species-specific markers. Previously, an insertion element was found within an A. pleuropneumoniae-specific gene commonly used for A. pleuropneumoniae detection, prompting the need for additional species-specific markers. Herein, 12 marker candidates highly conserved (99 - 100% identity) among 34 A. pleuropneumoniae genomes (covering 13 serovars) were identified to be A. pleuropneumoniae-specific , as these sequences are distinct from 30 genomes of 13 other and problematic [] species and more than 1700 genomes of other bacteria in the family. Five marker candidates are within the gene, a known A. pleuropneumoniae-specific gene, validating our marker discovery method. Seven other A. pleuropneumoniae-specific marker candidates within the , , , , and genes were validated by polymerase chain reaction (PCR) to be specific to 129 isolates of A. pleuropneumoniae (covering all 19 serovars), but not to four closely related species, four [] species, or seven other bacterial species. This is the first study to identify A. pleuropneumoniae-specific markers through genome mining. Seven novel A. pleuropneumoniae-specific DNA markers were identified by a combination of and molecular methods and can serve as additional or alternative targets for A. pleuropneumoniae diagnostics, potentially leading to better control of the disease. Species-specific markers are crucial for infectious disease diagnostics. Mutations within a marker sequence can lead to false-negative results, inappropriate treatment, and economic loss. The availability of several species-specific markers is therefore desirable. In this study, 12 DNA markers specific to A. pleuropneumoniae, a pig pathogen, were simultaneously identified. Five marker candidates are within a known A. pleuropneumoniae-specific gene. Seven novel markers can be used as additional targets in DNA-based diagnostics, which in turn can expedite disease diagnosis, assist farm management, and lead to better animal health and food security. The marker discovery strategy outlined herein requires less time, effort, and cost, and results in more markers compared with conventional methods. Identification of species-specific markers of other pathogens and corresponding infectious disease diagnostics are possible, conceivably improving health care and the economy.
Topics: Actinobacillus pleuropneumoniae; Animals; Bacterial Proteins; Genetic Markers; Genome, Bacterial; Pathology, Molecular; Pleuropneumonia; Polymerase Chain Reaction; Swine; Swine Diseases
PubMed: 34985298
DOI: 10.1128/spectrum.01311-21