Search

In order to characterize the in vivo lesions in the nasal cavities and lungs, twenty-eight rabbits were intranasally instilled with lipopolysaccharide (LPS) from P. multocida and then divided into seven groups according to euthanasia time. The nasal cavities and the lungs were processed for light microscopy, lectin histochemistry and transmission electron microscopy. Increased goblet cell activation and neutrophil infiltration were relevant changes in the nasal cavity. A predominantly interstitial pattern of diffuse alveolar damage and bronchopneumonic foci were the main lesions found in the lungs. LPS was found in the cytoplasm of ciliated cells, goblet cells, glandular cells, venular endothelial cells and neutrophils in the nasal cavity and in club cells, capillary endothelial cells and neutrophil in the lung. This study demonstrates that the LPS is able to cause lesions in the upper and lower respiratory tract, it binds to and is internalized by respiratory epithelial cells. Furthermore, it also traverses the intercellular spaces to reach the blood vessels, where it binds to and is internalized by neutrophil and red blood cells. These cells may then travel to the lungs where the LPS induces typical diffuse alveolar damage. This route of lung interstitial damage, to our knowledge, has not been described for this molecule or any known pathogen. Incluye referencias bibliográficas.

Dermonecrotic toxin (DNT) is an important bacterial virulence factor produced by the zoonotic pathogens Bordetella bronchiseptica and Pasteurella multocida. This study aims to explore the possibility of expressing different fragments of P. multocida toxin (PMT) in the chromosome of attenuated B. bronchiseptica to generate single-component mucosal vaccine candidates. To achieve this, a 954-bp fragment (basepairs 301 ∼ 1254) of the B. bronchiseptica aroA gene was replaced with an N-terminal, 930-bp fragment (basepairs 1-930; PMTN) or a C-terminal, 900-bp fragment (base pairs 2959 ∼ 3858; PMTC) of the PMT encoding gene toxA. The resulting strains, denoted as Bb-PMTN or Bb-PMTC, expressed PMTN and PMTC, as evidenced by ELISA using polyclonal against full-length of PMT. Phenotypical analyses revealed that Bb-PMTN and Bb-PMTC grew much slower than wild type strains in tryptic soy broth. These strains also displayed significantly decreased 161-fold-virulence compared to the wildtype strains in mouse models. Intranasal immunization of Bb-PMTN and Bb-PMTC in mice induced high levels of antibodies against B. bronchiseptica and PMT, as well as IFN-γ and IL-10 in mouse sera, and most importantly, high titers of sIgA in mouse lungs. Vaccination with these two engineering strains provided 100% protection of mice against lethal challenge with B. bronchiseptica and 80%∼100% protection against lethal challenge with PMT, with Bb-PMTN exhibiting 1.25-fold greater immunogenic efficacy over Bb-PMTC. This study highlights the use of B. bronchiseptica attenuated strains as live mucosal vectors to deliver heterologous antigens.

Infections secondary to Pasteurella multocida frequently occur in patients who have been exposed to domestic pets. Human infections caused by Pasteurella multocida vary in severity, and clinical features include localised cellulitis, osteomyelitis, systemic bacteraemia, meningitis and pneumonia. No vaccine has been developed against Pasteurella multocida; it is treated with antibacterial agents and, in most cases, surgical intervention. This article discusses the authors' experience in treating a woman with severe cellulitis and osteomyelitis on her hand caused by Pasteurella multocida. She refused surgical intervention and was successfully treated with honey-containing dressings and antibiotics after failure to heal following conservative treatment using conventional wound dressings combined with antibiotics.

Background: Pasteurella spp. can lead to fatal infections in humans. Objective: To assess prognostic factors of invasive pasteurellosis. Methods: We conducted a single retrospective cohort study of local versus invasive Pasteurella infections from January 1, 2005, to December 31, 2018, in the Amiens-Picardie University Hospital, France. Results: Forty-five (20.9%) invasive pasteurellosis and 22 (10.2%) complicated local infections were reported among a total of 215 Pasteurella infections. The mortality rate among invasive infections was 22.2% (10/ 45) whereas no death was recorded in local infections group. Non–drug-induced prothrombin time test

The ability to distinguish among the subspecies of Pasteurella multocida isolates is important epidemiologically; however, classification at the subspecies level based on the results of conventional biochemical tests (fermentation of sorbitol and dulcitol) is reportedly not accurate in all cases. Therefore, we developed a rapid, multiplex PCR assay to differentiate among the 3 subspecies of P. multocida. The PCR assay includes the P. multocida species–specific primers KMT1SP6 and KMT1T7 as an internal amplification control, with a newly designed gatD (galactitol-1-phosphate-5-dehydrogenase)-specific primer pair (unique for subsp. gallicida), and primers targeting a 16S rRNA gene region specific for subsp. septica. The subspecies specificity of the PCR was demonstrated by applying the test to a collection of 70 P. multocida isolates, including the Heddleston serovar reference strains; all isolates and strains were assigned correctly. The PCR assay is a sensitive, specific, and highly effective method for the identification of P. multocida subspecies, and an alternative to biochemical test–based differentiation. A possible relationship was noticed between P. multocida subspecies and lipopolysaccharide (LPS) genotype; all but one of the subsp. gallicida strains were isolated only from avian hosts and represented L1 LPS genotype. Subsp. multocida and subsp. septica isolates were classified into 5 and 4 different LPS genotypes, respectively, of which L3 was the only LPS genotype shared between these 2 subspecies.

This work modifies a loop-mediated isothermal amplification (LAMP) assay to detect the bovine respiratory disease (BRD) bacterial pathogens Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni in a colorimetric format on a farm. BRD causes a significant health and economic burden worldwide that partially stems from the challenges involved in determining the pathogens causing the disease. Methods such as polymerase chain reaction (PCR) have the potential to identify the causative pathogens but require lab equipment and extensive sample processing making the process lengthy and expensive. To combat this limitation, LAMP allows accurate pathogen detection in unprocessed samples by the naked eye allowing for potentially faster and more precise diagnostics on the farm. The assay developed here offers 66.7–100% analytical sensitivity, and 100% analytical specificity (using contrived samples) while providing 60–100% concordance with PCR results when tested on five steers in a feedlot. The use of a consumer-grade water bath enabled on-farm execution by collecting a nasal swab from cattle and provided a colorimetric result within 60 min. Such an assay holds the potential to provide rapid pen-side diagnostics to cattle producers and veterinarians.

Background Pasteurella multocida (P. multocida) infection can cause a series of diseases in different animals and cause huge economic losses to the breeding industry. P. multocida is considered to be one of the most significant pathogens in rabbits. In order to elucidate the pathogenic mechanism and innate immune response of P. multocida, an infection experiment was carried out in this study. Results Our results showed that the clinical symptoms of rabbits were severe dyspnoea and serous nasal fluid. During the course of the disease, the deaths peaked at 2 days post infection (dpi) and mortality rate was 60%. The pathological changes of the lung, trachea, and thymus were observed. In particular, consolidation and abscesses appeared in lung. Histopathologic changes in rabbits showed edema, hemorrhage, and neutrophil infiltration in the lung. P. multocida can rapidly replicate in a variety of tissues, and the colonization in most of the tested tissues reached the maximum at 2 dpi and then decreased at 3 dpi. The number of P. multocida in lung and thymus remained high level at 3 dpi. Toll-like receptors 2 and 4 signaling pathways were activated after P. multocida infection. The expression of Il1β, Il6, Il8, and Tnf-α was significantly increased. The expression of most proinflammatory cytokines peaked at 2 dpi and decreased at 3 dpi, and the expression trend of cytokines was consistent with the colonization of P. multocida in rabbit tissues. Conclusions The P. multocida can rapidly replicate in various tissues of rabbit and cause bacteremia after infection. TLRs signaling pathways were activated after P. multocida infection, significantly inducing the expression of proinflammatory cytokines, which is might the main cause of respiratory inflammation and septicemia.

Background Pasteurella multocida is an opportunistic pathogen causing porcine respiratory diseases by co-infections with other bacterial and viral pathogens. Various bacterial genera isolated from porcine respiratory tracts were shown to inhibit the growth of the porcine isolates of P. multocida. However, molecular mechanisms during the interaction between P. multocida and these commensal bacteria had not been examined. Methods This study aimed to investigate the interaction between two porcine isolates of P. multocida (PM2 for type D and PM7 for type A) with Aeromonas caviae selected from the previously published work by co-culturing P. multocida in the conditioned media prepared from A. caviae growth and examining transcriptomic changes using RNA sequencing and bioinformatics analysis. Results In total, 629 differentially expressed genes were observed in the isolate with capsular type D, while 110 genes were significantly shown in type A. High expression of genes required for energy metabolisms, nutrient uptakes, and quorum sensing were keys to the growth and adaptation to the conditioned media, together with the decreased expression of those in the unurgent pathways, including translation and antibacterial resistance. Conclusion This transcriptomic analysis also displayed the distinct capability of the two isolates of P. multocida and the preference of the capsular type A isolate in response to the tough environment of the A. caviae conditioned media. Therefore, controlling the environmental sensing and nutrient acquisition mechanisms of P. multocida would possibly prevent the overpopulation of these bacteria and reduce the chance of becoming opportunistic pathogens.

Bovine respiratory disease (BRD) is one of the most important diseases impacting the global cattle industry, resulting in significant economic loss. Commonly referred to as shipping fever, BRD is especially concerning for young calves during transport when they are most susceptible to developing disease. Despite years of extensive study, managing BRD remains challenging as its aetiology involves complex interactions between pathogens, environmental and host factors. While at the beginning of the twentieth century, scientists believed that BRD was only caused by bacterial infections (“bovine pasteurellosis”), we now know that viruses play a key role in BRD induction. Mixtures of pathogenic bacteria and viruses are frequently isolated from respiratory secretions of animals with respiratory illness. The increased diagnostic screening data has changed our understanding of pathogens contributing to BRD development. In this review, we aim to comprehensively examine experimental evidence from all existing studies performed to understand coinfections between respiratory pathogens in cattle. Despite the fact that pneumonia has not always been successfully reproduced by in vivo calf modelling, several studies attempted to investigate the clinical significance of interactions between different pathogens. The most studied model of pneumonia induction has been reproduced by a primary viral infection followed by a secondary bacterial superinfection, with strong evidence suggesting this could potentially be one of the most common scenarios during BRD onset. Different in vitro studies indicated that viral priming may increase bacterial adherence and colonization of the respiratory tract, suggesting a possible mechanism underpinning bronchopneumonia onset in cattle. In addition, a few in vivo studies on viral coinfections and bacterial coinfections demonstrated that a primary viral infection could also increase the pathogenicity of a secondary viral infection and, similarly, dual infections with two bacterial pathogens could increase the severity of BRD lesions. Therefore, different scenarios of pathogen dynamics could be hypothesized for BRD onset which are not limited to a primary viral infection followed by a secondary bacterial superinfection.

K9CATH is the sole cathelicidin in canines (dogs) and exhibits broad antimicrobial activity against both Gram-positive and Gram-negative bacteria. K9CATH also modulates inflammatory responses and binds to LPS. These activities depend on the secondary structure and a net-positive charge of the peptide. Peptidylarginine deiminases (PAD) convert cationic peptidyl arginine to neutral citrulline. Thus, we hypothesized that citrullination is a biologically relevant modification of the peptide that would reduce the antibacterial and LPS-binding activities of K9CATH. Recombinant PAD2 and PAD4 citrullinated K9CATH to various extents and circular dichroism spectroscopy revealed that both native and citrullinated K9CATH exhibited similar α-helical secondary structures. Notably, citrullination of K9CATH reduced its bactericidal activity, abolished its ability to permeabilize the membrane of Gram-negative bacteria and reduced the hemolytic capacity. Electron microscopy showed that citrullinated K9CATH did not cause any morphological changes of Gram-negative bacteria, whereas the native peptide caused clear alterations of membrane integrity, concordant with a rapid bactericidal effect. Finally, citrullination of K9CATH impaired its capacity to inhibit LPS-mediated release of proinflammatory molecules from mouse and canine macrophages. In conclusion, citrullination attenuates the antibacterial and the LPS-binding properties of K9CATH, demonstrating the importance of a net positive charge for antibacterial lysis of bacteria and LPS-binding effects and suggests that citrullination is a means to regulate cathelicidin activities.

Pasteurella multocida (P. multocida) infects the swine respiratory tract and mainly causes atrophic rhinitis (AR). Recently, many commercially inactivated and subunit vaccines have been used as preventive strategies. However, the best antigenic protein portion has not been selected, and the aluminum gel was used as the adjuvant, which may not induce full protection. P. multocida toxin (PMT) is the major virulence factor responsible for AR. PMT is a monomeric 146 kDa protein (approximately 1285 amino acids) encoded by the tox A gene. In this study, we expressed different fragments of recombinant PMT proteins, combined them with a water-in-oil-in-water adjuvant, and evaluated mice's immune response. The results indicated that the rPMT-C-immunized group showed significantly higher levels (p 0.05) of IgG, IgG2a antibody and interferon-γ, IL-12 cytokine expression than other groups. Furthermore, vaccination with rPMT-C recombinant protein can provide homologous and heterologous protection against P. multocida challenge. In conclusion, our approach may be feasible for developing an effective subunit vaccine against atrophic rhinitis with a cost-down simple ingredient.

A neonatal male injured by the family dog developed meningitis secondary to Pasteurella multocida . After initially defervescing with IV antibiotic treatment, he became febrile again, and imaging revealed a skull fracture and fluid collection. Following neurosurgical evacuation and an extended course of antibiotics, the patient was discharged home.

Duck cholera (duck hemorrhagic septicemia) is a highly contagious disease caused by

Pasteurella multocida is an important zoonotic pathogen that causes multiple diseases in both animals and humans. Test of good immunogenic proteins is beneficial for vaccine development and disease control. In the present study, we determined four novel immunogenic proteins of P. multocida by using 2-DE MALDI-TOF MS with immune serum. These four proteins included a trimethylamine-N-oxide reductase TorA, a translation elongation factor Ts, a phosphoglyceromutase PGAM, and a peroxiredoxin PrX. Among these proteins, TorA, Prx, and PGAM were successfully expressed by using E. coli. Western-blotting assays showed that recombinant TorA, Prx, and/or PGAM displayed good reactions with infectious sera of P. multocida serogroups A, B, D and F. Immunization of either rTorA, rPrx, and/or rPGAM induced significantly high levels of antibodies as well as IFN-γ, IL-4 and IL-10 in mice (P 0.01). Protective efficacy tests revealed that vaccination of either rTorA, rPrx, and/or rPGAM protected 60% ~ 80% of the tested mice against the challenge with P. multocida field isolate. Our results obtained from the present study suggest that these three proteins could be tested as good vaccine candidates against P. multocida infections.

Pasteurellosis is one of the rabbit's most bacterial severe diseases and leads to considerable financial damages in large production systems worldwide. Antibiotic use in animals may lead to antibiotic residues in animal products, including meat. Therefore, this study was designed to evaluate the potential role of grape seed extract (GSE) in treating Pasteurella multocida infection in rabbits. For this purpose, 45 weaned male New Zealand rabbits were divided into three groups; control, infected and infected‐GSE treated. Experimental P. multocida infection in rabbits induced a remarkable decrease in body weight, body weight gain, as well as microcytic hypochromic anaemia, leucocytosis, neutrophilia and lymphocytopenia. Also, a significant increase in the hepatic and renal injury biomarkers, in interleukin‐6, total globulin, α, β and γ globulins, as well as a marked reduction in total protein and albumin, were recorded in the P. multocida‐infected rabbits. Treatment of infected rabbits with GSE modulated most of these altered parameters. This study endorses the administration of GSE for the treatment of Pasteurellosis in rabbits. Further studies are required to identify the possible additional effects, appropriate doses and duration of the GSE therapy in rabbits Pasteurellosis., According to the authors' knowledge, no comprehensive work was dedicated to assess the possible impact of grape seed extract in treating of P. multocida infection in rabbits. Moreover, grape seed extract could represent a promising for enhancement of Pasteurellosis treatment in rabbits and reduction of ofloxacin side effects.

International audience; Background: Pasteurella multocida is a Gram-negative, non-motile, non-spore forming, and aerobic/anaerobic cocobacillus known as the causative agent of human and animal diseases. Humans can often be affected by cat scratch or bite, which may lead to soft tissue infections and in rare cases to bacteremia and septicemia. Commercial vaccines against this agent include inactivated, live attenuated, and non-pathogenic bacteria. Current vaccines have certain disadvantages such as reactogenicity or reversion to virulence. Therefore, the aim of this study was to reach a multi-epitope vaccine candidate that could be serotype independent and covers most incident serotypes of P. multocida. Methods: In this study, reverse vaccinology strategy was used to identify potentially immunogenic and protective epitopes. First, multiple alignments of different sequences of Pasteurella lipoprotein E (PlpE) from various serotypes of P. multocida were analyzed to identify the conserved regions. Bioinformatics tools were then applied to predict and select epitopes for further studies. Results: Three different conserved immunogenic regions were selected according to the selected criteria, and their various sequential orders were evaluated structurally by in silico tools to find the best order. Conclusion: In searching the epitopes of PlpE to design a new vaccine candidate against pasteurellosis, we found the region 1 + region 2 + region 3 (without any linker between regions) of epitope, including the regions of PlpE protein of P. multocida, as the appropriate serotype independent vaccine candidate against pasteurellosis.

This is a case of Pasteurella multocida septic shock encountered in a 7-week-old infant without any bites, scratch marks, or history of licks by pet animals (dog and cats in household). The infant required 3 days of vasopressor support and 4 days of mechanical ventilation to achieve normal hemodynamics. This is an unidentified route of transmission and our literature search for this topic discovered reported cases of life-threatening presentation with Pasteurella infections in the absence of a bite or any form of invasive contact with animals. We believe that this is an important public safety message to restrict animal contact of young infants to prevent severe infection.

A 33-day-old previously healthy term female is admitted to the pediatric intensive care unit with fever, lethargy and bulging fontanel. Given concern for meningitis, a lumbar puncture is performed and empiric treatment is initiated. The cerebrospinal fluid culture results reveal Pasteurella multocida. The patient is treated with intravenous ampicillin for 3 weeks and discharged with close outpatient follow-up.

The bacterial pathogen P. multocida can cause serious disease in production animals, including fowl cholera in poultry, hemorrhagic septicemia in cattle and buffalo, atrophic rhinitis in pigs, and respiratory diseases in a range of livestock. P. multocida produces a capsule that is essential for systemic disease, but the complete mechanisms underlying synthesis and regulation of capsule production are not fully elucidated. A whole-genome analysis using TraDIS was undertaken to identify genes essential for growth in rich media and to obtain a comprehensive characterization of capsule production.

Fowl cholera caused by

The pharmacokinetics of gamithromycin were evaluated in 26 male castrated and female crossbred swine administered gamithromycin 15% w/v (Zactran®, Boehringer Ingelheim) intravenously at 6 mg/kg bodyweight or intramuscularly at 3, 6 or 12 mg/kg bodyweight. Blood samples were collected up to Day 10 to establish the plasma profile of gamithromycin, bioavailability and dose proportionality. When administered by intramuscular injection at 6 mg/kg BWT, pharmacokinetic parameters were as follows: area under the curve until last quantifiable plasma concentration, 5.13 ± 0.957 µg*hours/ml; maximum plasma concentration, 960 ± 153 ng/ml at 5 to 15 min; terminal half‐life of 94.1 ± 20.4 hr. Absolute bioavailability was 92.2%. Increase in systemic exposure was proportional to the gamithromycin dose level over the range 3–12 mg/kg BWT. No gender‐related statistically significant difference in exposure was observed. For clinical evaluation of Zactran® against swine respiratory disease, 305 pigs from six commercial farms in three countries in Europe with signs associated with Actinobacillus pleuropneumoniae and/or Haemophilus parasuis and/or Pasteurella multocida and/or Bordetella bronchiseptica were used. At each site, animals were treated once in a 1:1 ratio with a single intramuscular dose of Zactran® (6 mg gamithromycin/kg bodyweight) or Zuprevo® (4% w/v tildipirosin at 4 mg/kg bodyweight; MSD Animal Health) at the recommended dose respectively. Animals were observed and scored daily for 10 consecutive days for signs of swine respiratory disease (depression, respiration and rectal temperature), and animals presenting signs of clinical swine respiratory disease (Depression Score 3 and/or Respiratory Score 3 associated with Rectal Temperature > 40.0°C) were removed from the study and considered as treatment failure. Animals which remained in the study were individually assessed for ʽtreatment successʼ or ʽtreatment failureʼ (Depression Score ≥ 1 and Rectal Temperature > 40.0°C or Respiratory Score ≥ 1 and Rectal Temperature > 40.0°C). Using a non‐inferiority hypothesis test (non‐inferiority margin = 0.10), the proportion of treatment successes in the Zactran® group (97%) was equivalent to or better than that in the Zuprevo® group (93%)., Intramuscular injection of gamithromycin 15% w/v in swine at 6 mg/kg is characterized by rapid absorption and distribution to tissues. Clinical evaluation in an European field study incorporating 305 swine has shown safe and efficacious treatment for swine with bacterial respiratory disease.

1, 25-dihydroxycholecalciferol is recognized as a potent immune-modulator which can fight against the pathogens via the activation of vitamin D3 receptors (VDRs), as well as stimulating various cytokines in infectious diseases. In the present study, because of the vitamin D3 has an appropriate immunomodulatory, the effects of this vitamin on the levels of pre-inflammatory and anti-inflammatory cytokines have been investigated in calves with experimental pasteurellosis. This study was experimentally carried out on 10 Holstein crossbred male calves (2–4 months) that were divided into two groups. Prepared Pasteurella multocida (3 × 109 CFU/mL) was inoculated in the trachea with a lavage catheter and then the treatment group was injected with 1, 25-dihydroxycholecalciferol after confirming pneumonia. Blood sampling, clinical symptoms scoring and radiological evaluation were recorded for both groups at different time intervals. The prescription of, vitamin D3 to the treatment group caused a decline in clinical symptoms score and changed interstitial and alveolo-interstitial lung pattern to such a degree that it could recover in comparison with the control group. The concentrations of pro-inflammatory cytokines (i.e., IL-1β, IL-6, and TNF-α) and the chemokine (IL-8) showed a significant decrease in the treatment group while the concentration of IL-10 increased in the treatment groups following the vitamin D3 injection (P = .001). The evidence from the current study suggests that vitamin D3 exert the immunomodulatory effects in infectious diseases through the regulation of cytokines and activation of VDR pathways to produce antimicrobial peptides.

Background Pasteurellosis (Pasteurella infection) is one of the most common bacterial infections in rabbits on commercial farms and in laboratory facilities. Curative treatments using antibiotics are only partly efficient, with frequent relapses. Breeding rabbits for improved genetic resistance to pasteurellosis is a sustainable alternative approach. In this study, we infected 964 crossbred rabbits from six sire lines experimentally with Pasteurella multocida. After post-mortem examination and bacteriological analyses, abscess, bacteria, and resistance scores were derived for each rabbit based on the extent of lesions and bacterial dissemination in the body. This is the first study to use such an experimental design and response traits to measure resistance to pasteurellosis in a rabbit population. We investigated the genetic variation of these traits in order to identify potential selection criteria. We also estimated genetic correlations of resistance to pasteurellosis in the experimental population with traits that are under selection in the breeding populations (number of kits born alive and weaning weight). Results Heritability estimates for the novel response traits, abscess, bacteria, and resistance scores, ranged from 0.08 (± 0.05) to 0.16 (± 0.06). The resistance score showed very strong negative genetic correlation estimates with abscess (− 0.99 ± 0.05) and bacteria scores (− 0.98 ± 0.07). A very high positive genetic correlation of 0.99 ± 0.16 was estimated between abscess and bacteria scores. Estimates of genetic correlations of the resistance score with average daily gain traits for the first and second week after inoculation were 0.98 (± 0.06) and 0.70 (± 0.14), respectively. Estimates of genetic correlations of the disease-related traits with average daily gain pre-inoculation were favorable but with high standard errors. Estimates of genetic and phenotypic correlations of the disease-related traits with commercial selection traits were not significantly different from zero. Conclusions Disease response traits are heritable and are highly correlated with each other, but do not show any significant genetic correlations with commercial selection traits. Thus, the prevalence of pasteurellosis could be decreased by selecting more resistant rabbits on any one of the disease response traits with a limited impact on the selection traits, which would allow implementation of a breeding program to improve resistance to pasteurellosis in rabbits.

This paper describes the first documented outbreak of haemorrhagic septicaemia (HS) caused by Pasteurella multocida type B in cattle in Spain. This acute, highly fatal septicaemia causes major economic losses in cattle and buffaloes in many areas of Asia and Africa. In other species and in European countries it is an infrequently reported disease. Acute septicaemic pasteurellosis occurred in a free-range farm of 150 cattle and 70 beef calves in Southern Spain. Twenty-one calves and one cow were affected, of which three calves and the adult cow died. Postmortem examination revealed characteristic oedema in the ventral area of the neck and the brisket region, and widespread haemorrhages in all organs. Pure cultures of P. multocida were obtained from all tissues and organs studied. The aetiological agent was further confirmed by molecular and biochemical analysis as P. multocida capsular type B, biovar 3. Although the source of infection could not be determined, wildlife may play an important role. The use of tulathromycin in the initial stage of the disease might be related to the low morbidity and mortality of this outbreak. After using an autogenous vaccine no more cases of HS were observed.

To evaluate the ability of inulin to enhance the immune response of a ptfA gene DNA vaccine for avian Pasteurella multocida, inulin was added as an adjuvant to the ptfA-DNA vaccine, obtaining an inulin-adjuvant DNA vaccine. The DNA vaccine was administered to chickens; a fimbria protein vaccine and an attenuated live vaccine were used as positive controls. The levels of the serum antibody and concentrations of interferon-γ (IFN-γ), interleukin-2 (IL-2), and interleukin-4 (IL-4) were determined, and a lymphocyte proliferation assay was performed. After being challenged with virulent P. multocida, the protective efficacy was evaluated. The results showed that the serum antibodies induced by the ptfA-DNA vaccine were not enhanced by inulin. The stimulation index values and the concentrations of IL-2 and IFN-γ in chickens vaccinated with inulin-adjuvant DNA vaccine were significantly higher than those in chickens vaccinated with the DNA vaccine, those with the fimbria protein vaccine, and the chickens gavaged with inulin. The concentrations of IL-4 in the inulin-adjuvant DNA vaccine group and the fimbria protein vaccine group were higher than those in the DNA vaccine group and the inulin-gavage group. The protective efficacy rates of the attenuated live vaccine group, the fimbria protein vaccine group, the DNA vaccine group, the inulin-adjuvant DNA vaccine group, and the inulin-gavage group were 90, 70, 55, 65, and 55%, respectively.

Pasteurella multocida is a part of the normal oral flora of domestic animals. Humans can develop skin and soft tissue infections from P. multocida after traumatic animal contact, usually through bites and scratches from domestic animals. Although rare, there have been documented case reports where P. multocida has been isolated from patients even after minimal casual animal contact. Even rarer, is the isolation of P. multocida from urine. The few documented cases of urine isolation have been described in patients who have underlying medical conditions, particularly those with urologic abnormalities. Here we present a 34-year-old female patient with known congenital neurological and urological anomalies who developed a P. multocida urinary tract infection from casual contact with a household feline, a previously unrecognized risk factor for P. multocida UTI in anatomically susceptible individuals.

Background Pasteurella multocida is one of the most significant pathogens for a number of animals. In rabbits, the infection is generally associated with the P. multocida serogroups A and D, and the knowledge about the serogroup F is limited. In the present study, a P. multocida serogroup F isolate designated s4 was recovered from the lungs of rabbits died of respiratory disease in Fujian, in the southeast of China. The pathogenicity and genomic features of the s4 were then determined. Results The serotype and sequence type of s4 were F:L3 and ST12, respectively. The s4 was pathogenic for rabbits, but it was a low virulent strain comparing to the previously reported highly pathogenic P. multocida serogroup F strains J-4103, C21724H3km7, P-4218 and HN07. The whole genome of the s4 was then sequenced to understand the genomic basis for pathogenicity. Particularly, a large-sized fragment of approximate 275 kb in length was truncated from the chromosome to form a plasmid. Moreover, the in-frame deletion of natC and N-terminal redundance of gatF would resulted in the production of a mutant L3 outer core structure that was distinct from those of the other P. multocida strains belonging to the lipopolysaccharide genotype L3. We deduced that these features detected in the genome of s4 might impair the pathogenicity of the bacterium. Conclusions This study evaluated the pathogenicity and determined the genomic features of the rabbit sourced P. multocida serogroup F isolate s4, the observations and findings would helpful for the understanding of the pathogenicity variability and genetic diversity of P. multocida.

BACKGROUND As a common member of the oral bacterial flora of cats and dogs, Pasteurella multocida can cause skin and soft tissue infection in humans after bites, licks, or scratches from animals. Uncommonly, infection due to Pasteurella can cause sepsis in humans. Even more rare is the development of infectious endocarditis from a Pasteurella infection. CASE REPORT A 76-year-old woman presented with malaise and symptoms of fluid overload. Blood cultures were positive for Pasteurella multocida, and an echocardiogram was significant for mitral valve vegetation and severe biatrial enlargement. A diagnosis of Pasteurella endocarditis was made. Surgical intervention was recommended, but owing to the risk involved, the patient elected for conservative management involving long-term treatment with intravenous antibiotics. CONCLUSIONS While exceedingly rare, Pasteurella multocida can cause infectious endocarditis in patients with predisposing factors. This patient had a known history of rheumatic heart disease, which is believed to have caused the significant findings on imaging. To the best of our knowledge, our case is the only one to depict Pasteurella endocarditis in a patient with rheumatic heart disease and severe biatrial enlargement. It is the authors' belief that the rheumatic heart disease and remodeling of the heart increased her susceptibility to severe infection from Pasteurella. The purpose of this case is to describe the pathogenicity of an otherwise low-attack bacterial infection in an elderly patient with underlying structural acquired heart damage.

Livestock is a fundamental part of the agriculture industry in Pakistan and contributes more than 11.53% to GDP. Among livestock species, the buffaloes are regarded as the black gold of Pakistan. Being the highest milk producers globally, Nili-Ravi buffaloes are the most famous ones. Buffaloes are affected by many endemic diseases, and "Hemorrhagic septicemia" (HS) is one of them. This study was designed to ascertain the effects of experimental exposure ofP. multocida B:2 (oral) and its immunogens, i.e., LPS (oral and intravenous) and OMP (oral and subcutaneous) on reproductive hormonal profiles in Nili-Ravi buffaloes. Repeated serum samples were collected from the jugular vein of experimental animals for 21 days (0, 02, 04, 08, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 and 504 hours). Hormonal assays to determine the serum concentrations of Gonadotropin-releasing hormone (GnRH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estrogen (E2) and progesterone (P4) were performed using (MyBioSource) commercial Elisa kits. The hormonal profile of all treatment groups of the buffalo heifers exhibited significant (P

Swine pneumonia commonly known as swine pasteurellosis is an infectious disease of swine caused by Pasteurella multocida infection. It has been reported that Toll-like receptors (TLRs) play a vital role in swine pneumonia progression. However, the underlying mechanism has not been elucidated. This research was aimed at investigating the molecular mechanism by which TLR9 regulates swine pneumonia progression. Our findings illustrated that the HD-13 strain of Pasteurella multocida D (HD-13) accelerated TLR9 expression in porcine alveolar macrophage 3D4/21 cells; HD-13 activated the inflammatory response via accelerating TLR9 expression. Mechanistically, HD-13 activated mitogen-activated protein kinase (MAPK) and nuclear factor kB (NF-κB) signals. In conclusion, HD-13 may activate MAPK and NF-κB pathways via accelerating TLR9 expression, thereby accelerating the inflammatory response in the progression of swine pneumonia. TLR9 may serve as a novel therapeutic target for swine pneumonia. Our research may provide a theoretical basis for the prevention and treatment of swine pneumonia.

Vaccines are very effective in providing protection against many infectious diseases. However, it has proven difficult to develop highly efficacious vaccines against some pathogens and so there is a continuing need to improve vaccine technologies. The first successful and widely used vaccines were based on attenuated pathogens (e.g., laboratory passaged Pasteurella multocida to vaccinate against fowl cholera) or closely related non-pathogenic organisms (e.g., cowpox to vaccinate against smallpox). Subsequently, live vaccines, either attenuated pathogens or non-pathogenic microorganisms modified to deliver heterologous antigens, have been successfully used to induce protective immune responses against many pathogens. Unlike conventional killed and subunit vaccines, live vaccines can deliver antigens to mucosal surfaces in a similar manner and context as the natural infection and hence can often produce a more appropriate and protective immune response. Despite these advantages, there is still a need to improve the immunogenicity of some live vaccines. The efficacy of injectable killed and subunit vaccines is usually enhanced using adjuvants such mineral salts, oils, and saponin, but such adjuvants cannot be used with live vaccines. Instead, live vaccines can be engineered to produce immunomodulatory molecules that can stimulate the immune system to induce more robust and long-lasting adaptive immune responses. This review focuses on research that has been undertaken to engineer live vaccines to produce immunomodulatory molecules that act as adjuvants to increase immunogenicity. Adjuvant strategies with varying mechanisms of action (inflammatory, antibody-mediated, cell-mediated) and delivery modes (oral, intramuscular, intranasal) have been investigated, with varying degrees of success. The goal of such research is to define adjuvant strategies that can be adapted to enhance live vaccine efficacy by triggering strong innate and adaptive immune responses and produce vaccines against a wider range of pathogens.

Pasteurella multocida, a Gram-negative bacterium with ubiquitous nature, is known to affect wide range of host species worldwide with varied clinical manifestations including haemorrhagic septicaemia (HS) in bovines. Although, HS causing P. multocida strains were identified and characterized by conventional tools and PCR assays, diverse strains are indistinguishable by these tools in the face of disease outbreaks. In this study, draft genomes of three virulent P. multocida serotype B:2 strains (NIVEDIPm32, NIVEDIPm34 and NIVEDIPm35) were analyzed following whole genome sequencing, assembly, annotation and compared them with existing global genomes (n = 43) of bovine origin in the database. Three draft genomes of NIVEDIPm strains consisted of 40-52 contigs with GC content of ∼40.4%. The genome size and predicted genes content was ∼2.3 Mb and 2181-2189, respectively. Besides, the presence of various mobile genetic elements, antimicrobial resistance genes and biofilm related genes suggested their vital roles in virulence; further, adaptation to the host immune system as well as host pathogen interaction. Multi locus sequence analysis based on RIRDC scheme showed the presence of ST122 in all the three strains. wgMLST based phylogenic analysis suggested that HS causing Indian virulent field strains differed geographically and showed diversity from existing HS vaccine strain P52. The phylogenetic tree revealed that North Indian strains share high similarity with strains of Pakistan than South Indian Strain. Notably, a high divergence of SNPs between the HS causing circulating virulent strains of India and current HS vaccine strain P52 suggested an imminent need for relook in to HS vaccination strategy for livestock in India.

Citrus limetta is well known for its anti-inflammatory, antimicrobial, antifungal, antidiabetic and antioxidant properties. Methanolic extract of Citrus limetta (MECL) was used to assess cellular and humoral immune responses in mice by carrying out cyclophosphamide-induced neutropenia, delayed-type hypersensitivity (DTH), carbon clearance assay, haemagglutination assay (HA) and mice lethality assay. Methanolic extract of Citrus limetta peel was administered orally to mice in two doses 200mg/kg and 400mg/kg.The extract treated groups showed improvement in neutropenia induced by cyclophosphamide and improvement in the WBC profile. Skin thickness was significantly (P0.05) higher in 200mg/kg and 400mg/kg groups in comparison to control in DTH. The phagocytic index was significantly (P0.05) more in 400mg/kg group in carbon clearance assay. Mice were vaccinated with hemorrhagic septicemia vaccine before challenge with Pasteurella multocida for mice lethality test. Percentage mortality was decreased in 400mg/kg treated group in comparison to negative control Antibody titre response to sheep red blood cells was significantly (P0.05) higher with dose 400mg/kg in HA. Results suggested the effectiveness of the methanolic extract of Citrus limetta as an immunostimulating agent.

QseC, a histidine sensor kinase of the QseBC two-component system, acts as a global regulator of bacterial stress resistance, biofilm formation, and virulence. The function of QseC in some bacteria is well understood, but not inPasteurella multocida. We found that deletingqseCinP. multocidaserotype A:L3 significantly down-regulated bacterial virulence. The mutant had significantly reduced capsule production but increased resistance to oxidative stress and osmotic pressure. DeletingqseCled to a significant increase inqseBexpression. Transcriptome sequencing analysis showed that 1245 genes were regulated byqseC, primarily those genes involved in capsule and LPS biosynthesis and export, biofilm formation, and iron uptake/utilization, as well as several immuno-protection related genes includingompA,ptfA,plpB,vacJ, andsodA. In addition to presenting strong immune protection againstP. multocidaserotypes A:L1 and A:L3 infection, live ΔqseCalso exhibited protection againstP. multocidaserotype B:L2 and serotype F:L3 infection in a mouse model. The results indicate that QseC regulates capsular production and virulence inP. multocida. Furthermore, theqseCmutant can be used as an attenuated vaccine againstP. multocidastrains of multiple serotypes.