Actinobacillus pleuropneumoniae: The molecular determinants of virulence and pathogenesis

Nahar, Nusrat; Turni, Conny; Tram, Greg; Atack, John M.

doi:10.1016/bs.ampbs.2020.12.001

Cited by 19 publications

(24 citation statements)

References 185 publications

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“…Some strains cause high mortality, while others are intermediate in virulence or avirulent. In addition to type 4 fimbria, outer membrane proteins, capsules, surface polysaccharides, lipopolysaccharide, biofilm formation capacity, extracellular enzymes, and toxins were identified as virulence factors [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The major virulence factors of A. pleuropneumoniae are exotoxins, which are RTX toxins (repeats in toxins).…”

Section: Introductionmentioning

confidence: 99%

Genetic Diversity of Actinobacillus pleuropneumoniae Serovars in Hungary

Kardos

Sárközi

Laczkó

et al. 2022

Veterinary Sciences

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A total of 114 Actinobacillus pleuropneumoniae isolates from porcine hemorrhagic necrotic pleuropneumonia were characterized by the examination of biotype, serovar, antibiotic resistance genes, and genes of toxin production. Pulsed-field gel electrophoresis was used to analyze their genetic relationship, which identified 16 clusters. Serovar 2 (50 isolates), serovar 13 (25 isolates), serovar 9 (11 isolates), and serovar 16 (7 isolates) were the most frequent serovars. Serovar 2 formed nine distinguishable clusters; serovar 13 and serovar 16 were less diverse, exhibiting two potentially related subclusters; serovar 9 was represented by a single cluster. Remarkably small differences were seen in the core genome when nine representative isolates of serovar 13 were subjected to whole-genome sequencing. Tetracycline resistance was relatively frequent in the two clusters of serovar 13; one of them was also frequently resistant against beta-lactams. Resistance in other serovars was sporadic. All isolates carried the apxIV gene. The toxin profiles of serovar 2 were characterized by the production of ApxII and ApxIII toxins, except for a small cluster of three isolates: serovar 9 and serovar 16 isolates produced ApxI and ApxII toxins. Serovar 13 carried apxII and apxIBD genes, indicating the production of the ApxII toxin, but not of ApxI or ApxIII. The unusually high frequency and low diversity of serovar 13 are not explained by its virulence properties, but the high frequency of resistance to beta-lactams and tetracyclines may have played a role in its spread. The emergence of serovar 16 may be facilitated by its high virulence, also explaining its high clonality.

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Section: Introductionmentioning

confidence: 99%

Genetic Diversity of Actinobacillus pleuropneumoniae Serovars in Hungary

Kardos

Sárközi

Laczkó

et al. 2022

Veterinary Sciences

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“…Actinobacillus pleuropneumoniae utilizes multiple virulence factors for pathogenesis. Adhesins, including fimbriae and pili, are involved in colonization ( 28 ). Several nutrient acquisition and uptake systems are reported to be necessary for growth within the host ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

A Combinatorial Vaccine Containing Inactivated Bacterin and Subunits Provides Protection Against Actinobacillus pleuropneumoniae Infection in Mice and Pigs

Zhang

Luo²,

Xiong³

et al. 2022

Front. Vet. Sci.

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Actinobacillus pleuropneumoniae (APP) is the etiological agent of porcine contagious pleuropneumonia (PCP) that causes great economic losses in the swine industry. Currently, vaccination is still a commonly used strategy for the prevention of the disease. Commercially available vaccines of this disease, including inactivated bacterins and subunit vaccines, have clinical limitations such as side effects and low cross-protection. In this study, a combinatorial vaccine (Bac-sub) was developed, which contained inactivated bacterial cells of a serovar 1 strain and three recombinant protoxins (rApxIA, rApxIIA, and rApxIIIA). Its side effects, immune protection, and cross-protection were evaluated and compared with a commercial subunit vaccine and a commercial trivalent bacterin in a mouse infection model. The results revealed that the Bac-sub vaccine showed no obvious side effects, and induced higher levels of Apx toxin-specific IgG, IgG1, and IgG2a than the commercial vaccines after booster. After a challenge with virulent strains of serovars 1, 5, and 7, the Bac-sub vaccine provided greater protection (91.76%, 100%, and 100%, respectively) than commercial vaccines. Much lower lung bacterial loads (LBLs) and milder lung lesions were observed in the Bac-sub-vaccinated mice than in those vaccinated with the other two vaccines. The protective efficacy of the Bac-sub vaccine was further evaluated in pigs, which showed that vaccinated pigs displayed significantly milder clinical symptoms and lung lesions than the unvaccinated pigs after the challenge. Taken together, Bac-sub is a safe and effective vaccine that could provide high protection against A. pleuropneumoniae infection in both mice and pigs.

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Section: Discussionmentioning

confidence: 99%

“…This variation in growth rate may give one population a selective advantage during long-term carriage. As biofilm formation is a key pathology of A. pleuropneumoniae (82, 83), strains encoding ModP1 could result in different disease outcomes, or even niche specific differences, dependent on the ON-OFF status of ModP1. Biofilm formation also increases resistance to antimicrobials (84–86), although we did not observe a difference in MIC with our ModP1 ON-OFF pair.…”

Section: Discussionmentioning

confidence: 99%

Actinobacillus pleuropneumoniaeencodes multiple phase-variable DNA methyltransferases that comprise distinct phasevarions

Nahar

Tram

Jen

et al. 2022

Preprint

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Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population of A. pleuropneumoniae strains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferase, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase variants results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions in A. pleuropneumoniae will aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.

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Actinobacillus pleuropneumoniae: The molecular determinants of virulence and pathogenesis

Cited by 19 publications

References 185 publications

Genetic Diversity of Actinobacillus pleuropneumoniae Serovars in Hungary

Genetic Diversity of Actinobacillus pleuropneumoniae Serovars in Hungary

A Combinatorial Vaccine Containing Inactivated Bacterin and Subunits Provides Protection Against Actinobacillus pleuropneumoniae Infection in Mice and Pigs

Actinobacillus pleuropneumoniaeencodes multiple phase-variable DNA methyltransferases that comprise distinct phasevarions

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