New trends in innovative vaccine development against Actinobacillus pleuropneumoniae

Loera-Muro, Abraham; Angulo, Carlos

doi:10.1016/j.vetmic.2018.02.028

Cited by 39 publications

(48 citation statements)

References 74 publications

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“…Commercial vaccines against App are currently based on toxins, attenuated strains and subunit vaccines or combinations of the above (1,6). They were shown to significantly reduce clinical symptoms in vaccinated pigs, but fail to achieve total protection and, most importantly, fail to protect against transmission, highlighting the importance for the development of new vaccines (1,6).…”

Section: Introductionmentioning

confidence: 99%

An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1

Budde

Litschko

Führing

et al. 2020

Journal of Biological Chemistry

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Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers.

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Section: Introductionmentioning

confidence: 99%

An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1

Budde

Litschko

Führing

et al. 2020

Journal of Biological Chemistry

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“…The strips were incubated with Dylight-800-conjugated goat anti-mouse IgG, and the images were captured with a scanned infrared imaging system. vaccine antigens are important approaches to overcome the deficiencies of current vaccines, and have received much attention in recent years 10 . Immunogenic proteins from the cell surface and outer membrane of A. pleuropneumoniae have been identified by phage display, immunoproteomic analysis or bioinformatic prediction 12,20,21 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide screening of lipoproteins in Actinobacillus pleuropneumoniae identifies three antigens that confer protection against virulent challenge

Cao

Gao

Zhang

et al. 2020

Sci Rep

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Actinobacillus pleuropneumoniae is an important veterinary pathogen that causes porcine pleuropneumonia. Lipoproteins of bacterial pathogens play pleiotropic roles in the infection process. In addition, many bacterial lipoproteins are antigenic and immunoprotective. Therefore, characterization of lipoproteins is a promising strategy for identification of novel vaccine candidates or diagnostic markers. We cloned 58 lipoproteins from A. pleuropneumoniae JL03 (serovar 3) and expressed them in Escherichia coli. Five proteins with strong positive signals in western blotting analysis were used to immunize mice. These proteins elicited significant antibody responses, and three of them (APJL_0922, APJL_1380 and APJL_1976) generated efficient immunoprotection in mice against lethal heterologous challenge with A. pleuropneumoniae 4074 (serovar 1), both in the active and passive immunization assays. Then immunogenicity of these three lipoproteins (APJL_0922, APJL_1380 and APJL_1976) were further tested in pigs. Results showed that these proteins elicited considerable humoral immune responses and effective protective immunity against virulent A. pleuropneumoniae challenge. Our findings suggest that these three novel lipoproteins could be potential subunit vaccine candidates.Actinobacillus pleuropneumoniae is a Gram-negative bacterium that colonizes the upper respiratory tract of pigs, and causes porcine pleuropneumonia, a common respiratory infection that is characterized as acute hemorrhagic to chronic necrotic-fibrinous pleuropneumonia and associated with significant economic losses in the pig industry worldwide 1 . Great efforts have been devoted to the characterization and control of porcine pleuropneumonia in the past 30 years, and considerable achievements have been made. A total of 18 serovars of A. pleuropneumoniae have been identified till now, all of these serovars are able to colonize pigs 2 . Since A. pleuropneumoniae is susceptible to drying and other antibacterial factors, direct transmission from infected to susceptible healthy pigs is considered to be the most frequent means by which the disease spreads 3 . Airborne transmission of A. pleuropneumoniae was also confirmed to occur over a short distance (1 m) 4 . Pigs of all ages are susceptible to A. pleuropneumoniae infection, especially fattening pigs at about 3-months old, and the first outbreak in herds often leads to high morbidity and mortality 5 . A. pleuropneumoniae contains several virulence factors, which are involved in the steps of adherence, colonization and tissue damage during infection, including Apx toxins, LPS, CPS, adhesins, outer membrane proteins, and transcriptional regulators 6 .Treatment of bacterial diseases of food-producing animals by extensive use of antimicrobial agents leads to antimicrobial resistance (AMR), a serious consequence that has attracted growing concerns worldwide 7 . The problem of AMR in A. pleuropneumoniae should not be underestimated at present 8 , and the use of drugs is undesirable for consumers of ethically produ...

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“…Actinobacillus pleuropneumoniae is a Gram-negative bacterial pathogen that preferentially infects and colonizes the lower respiratory tracts of pigs. It is the causative pathogen for the highly contagious porcine pleuropneumonia which is characterized by pulmonary edema, hemorrhage and necrosis (1,2). Acute outbreaks of A. pleuropneumoniae infection can result in swine death within 24 hours, leading to high economic losses for the swine industry (1,3).…”

Section: Introductionmentioning

confidence: 99%

“…It is the causative pathogen for the highly contagious porcine pleuropneumonia which is characterized by pulmonary edema, hemorrhage and necrosis (1,2). Acute outbreaks of A. pleuropneumoniae infection can result in swine death within 24 hours, leading to high economic losses for the swine industry (1,3). Antibiotic therapy is the most common and effective means of restricting the spread of infection and decreasing mortality.…”

Section: Introductionmentioning

confidence: 99%

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Actinobacillusutilizes a binding-protein dependent ABC transporter to acquire Vitamin B₆

Pan

Zimmer

Shah

et al. 2020

Preprint

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416) 946-3048; Running title: Structure and Function of a PLP periplasmic binding protein in Actinobacillus Biological Sciences, Microbiology AbstractBacteria require high efficiency uptake systems to survive and proliferate in nutrient limiting environments, such as those found in the host. The ABC transporters at the bacterial plasma membrane provide a mechanism for transport of many substrates. We recently demonstrated that an AfuABC operon, previously annotated as encoding a ferrous iron uptake system, is in fact a cyclic hexose/heptosephosphate transporter with high selectivity and specificity for these metabolites. In this study, we examine a second operon containing a periplasmic binding protein discovered in Actinobacillus for its potential role in nutrient acquisition. Using electron density obtained from the crystal structure of the periplasmic binding protein we modeled a pyridoxal-5'-phosphate (P5P/PLP/Vitamin B 6 ) ligand into the atomic resolution electron density map. The identity of the Vitamin B 6 bound to this periplasmic binding protein was verified by isothermal titration calorimetry, microscale thermophoresis, and mass spectrometry, leading us to name the protein P5PA and the operon P5PAB. To illustrate the functional utility of this uptake system, we introduced the P5PAB operon from A. pleuropneumoniae into an E. coli K-12 strain that was devoid of a key enzyme required for Vitamin B 6 synthesis. The growth of this strain at low levels of Vitamin B 6 supports the role of this newly identify operon in Vitamin B 6 uptake.

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New trends in innovative vaccine development against Actinobacillus pleuropneumoniae

Cited by 39 publications

References 74 publications

An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1

An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1

Genome-wide screening of lipoproteins in Actinobacillus pleuropneumoniae identifies three antigens that confer protection against virulent challenge

Actinobacillusutilizes a binding-protein dependent ABC transporter to acquire Vitamin B₆

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New trends in innovative vaccine development against Actinobacillus pleuropneumoniae

Cited by 39 publications

References 74 publications

An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1

An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1

Genome-wide screening of lipoproteins in Actinobacillus pleuropneumoniae identifies three antigens that confer protection against virulent challenge

Actinobacillusutilizes a binding-protein dependent ABC transporter to acquire Vitamin B6

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Product

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Actinobacillusutilizes a binding-protein dependent ABC transporter to acquire Vitamin B₆