Pasteurella Multocida Toxin

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Noncanonical G Protein Dependent Modulation of Osteoclast Differentiation and Bone Resorption Mediated by Pasteurella multocida Toxin

Noncanonical G Protein Dependent Modulation of Osteoclast Differentiation and Bone Resorption Mediated by Pasteurella multocida Toxin

IMPORTANCE Pasteurella multocida toxin (PMT) induces degradation of nasal turbinate bones, leading to the syndrome of atro- phic rhinitis. Recently, the molecular mechanism and substrate specificity of PMT were identified. The toxin activates heterotri- meric G proteins by a covalent modification. However, the mechanism by which PMT induces bone degradation is poorly under- stood. Our report demonstrates a direct effect of PMT on osteoclast precursor cells, leading to maturation of bone-degrading osteoclasts. Interestingly, PMT stimulates osteoclastogenesis independently of the cytokine RANKL, which is a key factor in in- duction of osteoclast differentiation. This implicates a noncanonical osteoclastogenic signaling pathway induced by PMT. The elucidated G ␣ q/11 -dependent osteoclastogenic signal transduction pathway ends in osteoclastogenic NFAT signaling. The nonca-
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Pasteurella multocida toxin- induced osteoclastogenesis requires mTOR activation

Pasteurella multocida toxin- induced osteoclastogenesis requires mTOR activation

Background: Pasteurella multocida toxin (PMT) is a potent inducer of osteoclast formation. Pigs suffering from an infection with toxigenic Pasteurella multocida strains develop atrophic rhinitis characterised by a loss of turbinate bones and conchae. However, on the molecular level the process of bone loss remains largely uncharacterised. Results: Recently it was found that PMT activates the serine/threonine kinase mammalian target of rapamycin (mTOR) in fibroblasts. Using RAW264.7 macrophages, we investigated the role of the mTOR complex 1 (mTORC1) in PMT-mediated osteoclast formation. PMT induces the differentiation of RAW264.7 macrophages into multinucleated, tartrate resistant acid phosphatase (TRAP) positive osteoclasts that are capable to resorb bone. In the presence of the mTORC1 inhibitor rapamycin, PMT was significantly less able to induce the formation of TRAP-positive osteoclasts. Accordingly, the resulting resorption of bone was strongly reduced. A major target of mTOR is the 70 kDa ribosomal protein S6 kinase 1 (p70 S6K1). Activated p70 S6K1 decreases the expression of programmed cell death protein 4 (PDCD4), a negative transcriptional regulator of osteoclastogenesis, at the protein and gene level. Ultimately this results in the activation of c-Jun, a component of the activator protein 1 (AP-1) complex, which is a major transcription factor for the induction of osteoclast-specific genes. We now demonstrate that c-Jun and its downstream target, the osteoclast-specific bone degrading protease cathepsin K, are upregulated upon PMT treatment in an mTOR-dependent manner.
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Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella multocida toxin-induced G protein signalling

Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella multocida toxin-induced G protein signalling

Antigen presenting cells are crucial for the first-line host defence and act as mediators between innate and adap- tive immunity. One major pathway of these cells involves TLR-mediated signalling events, which can detect and react to extracellular as well as intracellular microbial components [39,40]. To be effective, immune responses need the crosstalk between TLR-mediated and other sig- nalling cascades that play a role in immune responses or other cellular pathways, respectively. These interactions can have synergistic effects but can also antagonise responses in order to prevent excessive inflammation. To modify and presumably escape the host ’ s immune re- sponse pathogens have developed various strategies to interfere with signalling cascades of the host [41,42]. Be- sides direct inhibition or modification of TLR signalling, induction of alternative regulative or antagonistic en- dogenous signalling cascades is another strategy in im- mune evasion. Here, we investigated how the activation of heterotrimeric G proteins through the bacterial toxin PMT modulates TLR4-mediated activation of human blood-derived monocytes and how this potentially affects cells of the adaptive immune system such as T cells.
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Protective Immunity Conferred by the C-Terminal Fragment of Recombinant Pasteurella multocida Toxin

Protective Immunity Conferred by the C-Terminal Fragment of Recombinant Pasteurella multocida Toxin

Immunization and challenge in swine. In the swine experiments, 12 pregnant sows (crossbreed of Yorkshire and Landrace) used to produce three-way cross hybrid piglets (Yorkshire ⫻ Landrace ⫻ Duroc) were selected from commercial farms. They were randomly divided and immu- nized with PBS as a negative control (group A; 2 sows) or with the com- mercial vaccine for porcine respiratory disease (group B; 2 sows), toxoid (group C; 4 sows), or PMT2.3 (group D; 4 sows). Before the experiment, all sows were examined to determine whether they were preinfected with P. multocida and B. bronchiseptica. Pregnant sows were intramuscularly vaccinated twice at 5 and 2 weeks before parturition. One dose of the injection comprised 15 mg of PMT2.3 in 10% aluminum hydroxyl gel in group D and the equivalent amount of toxoid in group C. The adminis- tration of the commercial vaccine in group B was performed according to the manufacturer’s instructions.
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Studies on the mechanism of action of the potent mitogen Pasteurella multocida toxin

Studies on the mechanism of action of the potent mitogen Pasteurella multocida toxin

indeed, many bacterial toxins resemble glycoprotein hormones and have sequences homologous to other ligands . For example amino acid sequence homologies have been demonstrated among the A and B chains of cholera toxin, thyrotropin, lutenizing hormone, follicle-stimulating hormone and interferon. Such structural similarities also suggest similar uptake and processing mechanisms (MkJdlebrook and Borland, 1984). The cell surface receptor for cholera toxin has been demonstrated to be the ganglioside Gmi . however another glycoprotein has also been implicated. Similarly the receptor for diptheria toxin is thought to be complex and to involve more than one molecule (reviewed in Madshus and Stenmark, 1992). The vast number of discrepancies found between the number of cell surface binding sites and the number of toxin molecules required to elicit maximal biological effect, suggests that many of the binding sites are non-productive. For example as few as 4 to 10 molecules of active cholera toxin can effect maximal stimulation of adenylate cyclase (Gill, 1975) whereas only a single molecule of activated diptheria toxin is sufficient to cause cell death. As the toxins recognise receptors which are probably reserved for other ligands or functions this might explain why many more molecules are delivered intracellularly than are required to attain a maximal biological response. In addition, if these non-productive binding sites represent different proteins then the identity of the true functional receptor is more difficult to elucidate.
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Comparison of standardised versus non-standardised methods for testing the in vitro potency of oxytetracycline against mannheimia haemolytica and pasteurella multocida

Comparison of standardised versus non-standardised methods for testing the in vitro potency of oxytetracycline against mannheimia haemolytica and pasteurella multocida

Please cite this article as: P. Lees, J. Illambas, L. Pelligand, P.-L. Toutain, Comparison of standardised versus non-standardised methods for testing the in vitro potency of oxytetracycline against mannheimia haemolytica and pasteurella multocida, The Veterinary Journal (2016), http://dx.doi.org/doi: 10.1016/j.tvjl.2016.11.006.

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Original Article Antibacterial activity and mechanism of berberine on avian Pasteurella multocida

Original Article Antibacterial activity and mechanism of berberine on avian Pasteurella multocida

In our previous study, extract of Rhizoma copti- dis from Sichuan of China and Cortex phello- dendri had showed a strong antibacterial activ- ity in vitro against P. multocida [5]. Berberine, a main active ingredient of Rhizoma coptidis and Cortex phellodendri, has anti-inflammatory [6, 7], antimicrobial [8, 9], and antiviral effects [10]. In recent years, berberine as a broad- spectrum antimicrobial agent has attracted more and more attention [11, 12]. However, so far there are no available reports about antibac- terial activity and mechanism of berberine on P. multocida, or continueing in-depth exploration.
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A Novel aadA Aminoglycoside Resistance Gene in Bovine and Porcine Pathogens

A Novel aadA Aminoglycoside Resistance Gene in Bovine and Porcine Pathogens

FIG 1 Genomic context, sequence identity, and structural homology modeling of the aadA31 gene detected in P. multocida PM13 and H. somni HS31. (A) Genomic BLAST comparison of the PM13 and HS31 cosmid sequences, highlighting the insertion containing aadA31. The aadA31 gene is absent from M. haemolytica M42548 but resides with the ISPst2 element in a variant region syntenous with ICEMh1. The aadA31 gene is also present in the genome of M. bovoculi MB58069. (B) Gene context schematic of the insertion, depicting the novel insertion sequence from HS31 and the tetR-tetH duplication (truncated tetH* is represented as two arrows; truncated tetR is not shown). An expanded view of the ISPst2 left terminal inverted repeat (IR) showing the putative promoter for aadA31 ( ⫺ 35 and ⫺ 10 boxes in bold) is also presented. ISPst2 is inversely oriented such that the left inverted repeat is 58 bp from the aadA31 start codon. (C) Predicted amino acid (aa) sequence pairwise identity matrix of aadA homologues (only those with ⬎ 50% amino acid sequence identity in the CARD database). Shown at the bottom are the percent amino acid sequence identity values of selected AadA enzymes. (D) Predicted RobettaCM (21) ribbon model of the overall structure of AadA31. The N terminus is blue, and the C terminus is red. Conserved active site residues (20) are represented by sticks. (E) Superposition of the structures of AadA31 (orange) and AadA LT2 (light blue) (F) Electrostatic surface potential of AadA31 (showing orientations 90°
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Characteristics and biotypes of Pasteurella multocida isolated from humans

Characteristics and biotypes of Pasteurella multocida isolated from humans

The current data show that with tive for nitrite, and iii reluctance to grow in the exception of maltose fermentation, the cat- peptone broth due either to low salt content or associated[r]

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Capsular Polysaccharide Interferes with Biofilm Formation by Pasteurella multocida Serogroup A

Capsular Polysaccharide Interferes with Biofilm Formation by Pasteurella multocida Serogroup A

P asteurella multocida is a zoonotic (1), Gram-negative bacterium in the family Pasteurellaceae. P. multocida is part of the normal microbial flora of the upper respiratory tract of many animal species but is also a potential pathogen of many domestic and agriculturally important animals, such as dogs, cats, cattle, pigs, and avian species (2). P. multocida is also an important human pathogen following direct inocu- lation into subcutaneous tissues (e.g., bite wounds) (3). In hosts in which the innate immune response is compromised (such as prior viral infection, immunosuppression, stress, etc.) P. multocida is able to gain access to the lower respiratory tract and cause respiratory disease and systemic infection. In swine, P. multocida can cause a chronic polymicrobial infection (usually with Bordetella bronchiseptica) called atrophic rhinitis (4–6). However, P. multocida is not considered part of the normal flora of birds, in which it can be a highly invasive primary pathogen (7). Nonetheless, birds that recover from infection and obtain specific immunity can remain colonized by P. multocida, resulting in asymptomatic carriage and spread of the organism to nonimmune birds (8–10). Furthermore, birds can also become colonized with low-virulence P. multocida strains (11, 12). An important question is whether low-virulence strains can revert to a highly virulent phenotype if they infect naive animals. An essential virulence factor of P. mul- tocida is a glycosaminoglycan capsular polysaccharide (CPS) that helps shield other surface antigens from the host immune system (13) and prevent phagocytosis and bactericidal activity, among other roles (14). There are five P. multocida CPS serogroups based on capsular antigens of distinct structural and antigenic specificity, designated A (15), B, D, E (16), and F (17). CPS serogroup A is composed of hyaluronic acid, serogroup D is a polysaccharide susceptible to enzymes that degrade chondroitin sulfates A and C and heparinase, and serogroup F is a polysaccharide similar to chondroitin (18). The serogroup B CPS is composed predominately of mannose but also contains arabinose and galactose, while the composition of the CPS of serogroup E strains has not been determined (14).
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Identification of Pasteurella multocida and Pasteurella haemolytica by API 20E, Minitek, and Oxi/Ferm systems

Identification of Pasteurella multocida and Pasteurella haemolytica by API 20E, Minitek, and Oxi/Ferm systems

haemolytica DISCUSSION are listed as 100% positive for xylose in the data The results obtained from the rapid identifi- base of the Minitek system; however, in this cation systems includ[r]

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Pasteurella multocida subsp multocida and P  multocida subsp septica Differentiation by PCR Fingerprinting and α Glucosidase Activity

Pasteurella multocida subsp multocida and P multocida subsp septica Differentiation by PCR Fingerprinting and α Glucosidase Activity

Pasteurella species have been isolated from various animals, either as saprophytes in the nasopharynx or gastrointestinal tract or as primary pathogens (reviewed in reference 17). Hu- man disease is generally associated with some form of animal contact, most commonly a dog bite or cat bite or scratch (13, 14, 27, 30). Taxonomic relationships and nomenclature for this genus have undergone considerable change throughout the years. In 1985, DNA hybridization studies performed by Mut- ters et al. (22) revealed three homology groups of Pasteurella multocida that differed sufficiently enough from each other that they qualified as different species of Pasteurella. However, be- cause the recommended therapy for human infection with Pas- teurella is generally the same regardless of the species involved (reviewed in reference 17), the three groups of P. multocida were assigned different subspecies names for epidemiological purposes. P. multocida subsp. multocida includes the dulcitol- negative, sorbitol-positive isolates; P. multocida subsp. septica includes the dulcitol-negative, sorbitol-negative isolates; and P. multocida subsp. gallicida includes the dulcitol-positive iso- lates.
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Post-antibiotic eff ect of marbofl oxacin, enrofl oxacin and amoxicillin against selected respiratory pathogens of pigs

Post-antibiotic eff ect of marbofl oxacin, enrofl oxacin and amoxicillin against selected respiratory pathogens of pigs

A significant concentration-dependent increase in the duration of PAE was detected for both fluo- roquinolones. The same observation was demon- strated in other studies (Carbone et al. 2001; Zhao et al. 2014). In similar studies, the PAE effect of enrofloxacin was shorter compared with the results of our study – around three hours in Gram-negative bacteria (E.coli, S. Typhimurium, P. multocida) fol- lowing a 2-hour exposure to 8 × MIC. Direct com- parison with other studies is rather difficult due to differences in the characteristics of pathogens and strains (MIC and origin) and methodology (espe- cially detection) (Wetzstein 1994).
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Ribotype diversity of porcine Pasteurella multocida from Australia

Ribotype diversity of porcine Pasteurella multocida from Australia

found that with the porcine isolates, almost half of the multi- isolate ribotypes (6 of 14) contained multiple biovars. However our current study has also found that of the eight farms that had multiple isolates of different biovars, ribotyping confirmed that multiple ribotypes were present on all eight farms. For the eight farms with multiple isolates of the same biovar, ribotyping iden- tified multiple ribotypes in three. Based upon the methods described in this study, ribotyping is a better tool than biotyping for the purpose of establishing if different “types” of P multocida are present on a farm. Our results indicate that, in the absence of a capacity to perform ribotyping, biotyping may give some idea of the diversity of P multocida present in a pig herd, although the use of biotyping is likely to give an under-estimate of diversity.
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Porcine Respiratory Pathogens in Swine Farms Environment in Mexico

Porcine Respiratory Pathogens in Swine Farms Environment in Mexico

Figure 1. (a) Ethidium bromide stained of Actinobacillus pleuropneumoniae apxIVAN amplicon. Lane 1—1 kbp ladder. Lanes 2 to 6 swine farm environmental samples (drinking water). Lane 7—A. pleuropneumoniae S1 S-4074 (positive control). Lane 8—no template control (negative control); (b) Ethidium bromide stained of Haemophilus parasuis 16S rRNA amplicon. Lane 1—1 kbp ladder. Lane 2—Empty; Lane 3—no template control (negative control) Lane 4—H. parasuis serotype 5 (Nagazaki) (positive control). Lanes 5 to 20 swine farm environmental samples (5 and 6 food samples, 7 to 11 air samples, 12 to 16 nasal samples, 17 and 18 urine samples, 19 and 20 soil samples); (c) Ethidium bromide stained of Pasteurella multocida ToxA ampli- con. Lane 1—1 kbp ladder. Lane 2—no template control (negative control). Lane 3—P. multocida serotype 4 S-4056 (type D, DNT+) (positive control). Lane 4 to 19 swine farm environmental samples (4 to 6 and 14 nasal samples, 7 to 9 and 15 soil samples, 10 and 11 air samples, 12 drinking water samples, 16 to 19 food samples); (d) Ethidium bromide stained of Streptococcus suis cps2J and 16S rRNA amplicon. Lane 1—1 kbp ladder. Lane 2—Empty. Lane 3—no template control (negative control). Lane 4—S. suis serotype 2 (735) (positive control). Lanes 5 to 20 swine farm environmental samples (5 to 8 food samples, 9 to 12 soil samples, 13 to 15 air samples, 16 to 20 drinking water samples); (e) Ethidium bromide stained of PRRSV amplicon. Lane 1—1 kbp ladder. Lane 2—no template control (negative control). Lane 3—PRRSV (American type) (positive control). Lanes 4 to 16—swine farm environmental samples (4, 10, 11 and 14 nasal samples, 5, 7, 9 and 12 drinking water samples, 8, 11 and 13 soil samples, 15 and 16 food samples); (f) Ethidium bromide stained of swine influenza virus H1 and H3 amplicon. Lane 1—1 kbp ladder. Lane 2—no template control (negative control). Lane 3—SIV (HIN1 and H3N2) (positive control). Lanes 4 to 20—swine farm environ- mental samples (5 to 7 and 18 soil samples, 8, 9, 14 and 20 nasal samples, 10, 12, 13 and 17 food samples, 11,
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Potency of marbofloxacin for pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida: Comparison of growth media

Potency of marbofloxacin for pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida: Comparison of growth media

MICs were determined by microdilution for six isolates each of A. pleuropneumoniae and P. multocida, in accordance with CLSI guidelines, except for: (a) using five sets of overlapping two-fold serial dilutions to increase accuracy; (b) making determinations in serum as well as broth; and (c) growing cultures to 0.5 McFarland Standard (approximately 1-2x10 8 CFU/mL) and this was diluted ten-fold to obtain a starting inoculum of 2x10 7 CFU/mL. This is higher than, and therefore also a deviation from the CLSI guidelines, which recommend a starting count of 5x10 5 CFU/mL. The higher count was selected to provide a medium to heavy microbial load.
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Insights into Pasteurellaceae carriage dynamics in the nasal passages of healthy beef calves

Insights into Pasteurellaceae carriage dynamics in the nasal passages of healthy beef calves

We investigated three bovine respiratory pathobionts in healthy cattle using qpcR optimised and validated to quantify Histophilus somni, Mannheimia haemolytica and Pasteurella multocida over a wide dynamic range. A longitudinal study was conducted to investigate the carriage and density of these bacteria in the nasal passages of healthy beef calves (n = 60) housed over winter in an experimental farm setting. The three pathobiont species exhibited remarkably different carriage rates and density profiles. At housing, high carriage rates were observed for P. multocida (95%), and H. somni (75%), while fewer calves were positive for M. haemolytica (13%). Carriage rates for all three bacterial species declined over the 75-day study, but not all individuals became colonised despite sharing of environment and airspace. Colonisation patterns ranged from continuous to intermittent and were different among pathobiont species. Interval-censored exponential survival models estimated the median duration of H. somni and P. multocida carriage at 14.8 (CI 95% : 10.6–20.9) and 55.5 (CI 95% : 43.3–71.3) days respectively,
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The effect of concurrent infections with Pasteurella multocida and Ascaridia galli on free range chickens

The effect of concurrent infections with Pasteurella multocida and Ascaridia galli on free range chickens

One hundred 16-week-old Lohmann Brown female chickens with no history of fowl cholera in previous or present ¯ocks on the farm were used for each experiment. The chickens were randomly distributed into ®ve groups each consisting of 20 individually identi®ed animals. Two weeks before the onset of the study all birds were examined for the presence of P. multocida by taking swabs from the cloaca, dissolving the swabs in saline water and subsequently injecting white balb/cJ mice with the solution as described by Muhairwa et al. (2000). Furthermore, a faecal sample from each bird was examined for the presence of parasites using the McMaster concentration techniques (Permin and Hansen, 1998). Regardless of the parasite status all the birds were treated with ¯ubendazole (7 mg/ kg live weight per 3 days) to ensure no interference from a low grade parasite infection.
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Usefulness of bixa orellana leaf extract against some veterinary pathogens

Usefulness of bixa orellana leaf extract against some veterinary pathogens

liquid with sweet odor. Antibacterial activity of the B. orellana leaf ethanolic extract through minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) showed that all test organisms were inhibited at 0.3125 mg/mL and killed at 2.5 mg/mL of the extract (Table 1). Among organisms used, Staphylococcus aureus was most susceptible having the lowest MIC at 0.078 mg/mL (Figure 1). The MIC of Salmonella pullorum was 0.1563 mg/mL and 0.3125 mg/mL for Enterococcus faecalis and Pasteurella multocida.

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The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study

The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study

As expected, castration led to weak clinical state, how- ever, in the untreated groups, castration did not worsen reisolation and laboratory parameters after infection with P. multocida . On the other hand, testosterone treat- ment of castrated animals seems to cause anaemia and weaker bactericidal capacity when compared to non- castrated and testosterone-treated rats, but better WBC and CRP results when compared to the castrated, un- treated group. Testosterone treatment of non-castrated animals resulted in stronger bactericidal effect (less rei- solated bacteria) and lower WBC count after infection compared to the non-castrated, untreated group. Taken to- gether, testosterone seems to improve the levels of inflam- matory parameters compared to the respective control.
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