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Pasteurella multocida serogroup F can infect a number of animals. However, the pathogenicity and genomic features of this serogroup are still largely unknown. In the present study, the pathogenicity and genomic sequences of 19 rabbit-sourced P. multocida serogroup F isolates were determined. The 19 isolates were highly pathogenic for rabbits causing severe pathologic lesions and high mortality in inoculated rabbits. Nevertheless, the pathologic lesions in rabbits caused by the 19 isolates were distinct from those caused by the previously reported high-virulent serogroup F strains J-4103 (rabbit), P-4218 (turkey), and C21724H3km7 (chicken). Moreover, the 19 isolates were avirulent to white feather broilers. The genomes of the 19 isolates were determined to understand the pathogenicity of these isolates. The finding of a number of functional genes in the 19 isolates by comparison with the low-virulent rabbit-sourced serogroup F strain s4 might contribute to the high virulence of these isolates. Notably, polymorphisms were determined in the lipopolysaccharide outer core biosynthetic genes natC and gatF among the serogroup F strains of different hosts. However, the sequences of natC and gatF from rabbit-sourced strains (except for SD11) were identical, which might be responsible for the host specific of the 19 isolates. The observations and findings in this study would be helpful for the understanding of the pathogenicity variation and host predilection of P. multocida ., Importance: The 19 rabbit-sourced Pasteurella multocida serogroup F isolates showing high virulence to rabbits were avirulent to the broilers. Notably, polymorphisms were determined in the lipopolysaccharide outer core biosynthetic genes natC and gatF among all serogroup F strains of different hosts. However, the sequences of natC and gatF from rabbit-sourced strains (except for SD11) were identical, which might be responsible for the host specific of the 19 isolates., Competing Interests: The authors declare no conflict of interest.

We have previously demonstrated that Slc6a13-deficient (Slc6a13-/-; KO) mice are resistant to P. multocida infection, which might be in connection with macrophage-mediated inflammation; however, the specific metabolic mechanism is still enigmatic. Here we reproduce the less sensitive to P. multocida infection in overall survival assays as well as reduced bacterial loads, tissue lesions, and inflammation of lungs in KO mice. The transcriptome sequencing analysis of wild-type (WT) and KO mice shows a large number of differentially expressed genes that are enriched in amino acid metabolism by functional analysis. Of note, glycine levels are substantially increased in the lungs of KO mice with or without P. multocida infection in comparison to the WT controls. Interestingly, exogenous glycine supplementation alleviates P. multocida infection-induced inflammation. Mechanistically, glycine reduces the production of inflammatory cytokines in macrophages by blocking the activation of inflammasome (NALP1, NLRP3, NLRC4, AIM2, and Caspase-1). Together, Slc6a13 deficiency attenuates P. multocida infection through lessening the excessive inflammatory responses of macrophages involving glycine-inflammasome signaling., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Pasteurella multocida B:2 causes haemorrhagic septicaemia in cattle and buffaloes. However, buffaloes are found to be more susceptible to the infection than cattle. Upon infection, the pathogen rapidly spread from the respiratory tract to the blood circulation within 16-72 h, causing septicaemia. So far, limited study has been conducted to evaluate the response of endothelial cells of buffalo towards P. multocida B:2 and its lipopolysaccharide (LPS). This study aimed to evaluate the ultrastructural changes in the aortic endothelium of buffaloes (BAEC) following exposure to P. multocida B:2 and its endotoxin. The endothelial cells were harvested from the aorta of healthy buffaloes and were prepared as monolayer cell cultures. The cultures were divided into 3 groups before Group 1 was inoculated with 10 7  cfu/ml of whole cell P. multocida B:2, Group 2 with LPS, which was extracted earlier from 10 7  cfu/ml of P. multocida B:2 and Group 3 with sterile cell culture medium. The cells were harvested at 0, 6, 12, 18, 24, 36, and 48 h post-inoculation for assessment of cellular changes using transmission electron microscopy., Results: The BAEC of Groups 1 and 2 demonstrated moderate to severe endothelial lysis, suggestive of acute cellular injury. In general, severity of the ultrastructural changes increased with the time of incubation but no significant difference (p > 0.05) in the severity of the cellular changes between Groups 1 and 2 was observed in the first 18 h. The severity of lesions became significant (p < 0.05) thereafter. Both treated Groups 1 and 2 showed significantly (p < 0.05) more severe cellular changes compared to the control Group 3 from 6 h post-inoculation. The severity reached peak at the end of the study period with score 3 for Group 1 and score 2.8 for Group 2., Conclusions: This study revealed that both whole cells P. multocida B:2 and LPS endotoxin showed similar moderate to severe cellular damage, but whole-cell P. multocida B:2 appeared to be more potent in causing much severe damage than LPS alone.

Pasteurella multocida is an important veterinary pathogen able to infect a wide range of animals in a broad spectrum of diseases. P. multocida is a complex microorganism in relation to its genomic flexibility, host adaptation and pathogenesis. Epidemiological analysis based on multilocus sequence typing, serotyping, genotyping, association with virulence genes and single nucleotide polymorphisms (SNPs), enables assessment of intraspecies diversity, phylogenetic and strain-specific relationships associated with host predilection or disease. A high number of sequenced genomes provides us a more accurate genomic and epidemiological interpretation to determine whether certain lineages can infect a host or produce disease. Comparative genomic analysis and pan-genomic approaches have revealed a flexible genome for hosting mobile genetic elements (MGEs) and therefore significant variation in gene content. Moreover, it was possible to find lineage-specific MGEs from the same niche, showing acquisition probably due to an evolutionary convergence event or to a genetic group with infective capacity. Furthermore, diversification selection analysis exhibits proteins exposed on the surface subject to selection pressures with an interstrain heterogeneity related to their ability to adapt. This article is the first review describing the genomic relationship to elucidate the diversity and evolution of P. multocida., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

This study reports the pathological and microbiological findings of pneumonia in a Mico melanurus caused by Pasteurella canis, confirmed for molecular analyses. It demonstrated the importance that wild species represent in the epidemiology of pasteurellosis in anthropic environments, when inserted into urban areas., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pasteurella multocida is an economically important respiratory pathogen of pigs confronting swine industry worldwide. Despite extensive research over the decades, its pathogenesis is still poorly understood. Recent reports have demonstrated the nervous system affection as a newer aspect of pathogenesis by Pasteurella multocida type B:2 in Haemorrhagic Septicemia, but there are no reports of the involvement of nervous system by P. multocida in pigs. Therefore, the study was aimed to explore the neurovirulence of Pasteurella multocida in naturally infected pigs. A total of 15 brains were collected from the natural cases of pig mortality suggestive of Pasteurellosis. Grossly, the leptomeninges were markedly congested and brains were oedematously swollen. Histologically, there was moderate to severe fibrinohaemorrhagic and mononuclear cells exudates present in the leptomeningeal tissue and cerebrospinal spaces. Similar vascular inflammatory lesions (perivascular and perineuronal) along with gliosis, neuronal degeneration and necrosis were noted in various subanatomical sites of the brain (cerebrum, cerebellum, brainstem and spinal cord). The culture and biochemical tests showed the presence of P. multocida within the brain tissue. P. multocida type specific antibody staining in the brain tissues revealed intense distribution of antigens in the inflammatory exudates of meningeal vessels, neurons, glial cells and endothelial cells of the blood vessels contributing its association with neuropathological lesions. Pasteurella multocida specific PCR amplification of capsular polysaccharide gene yielded 460 bp and multiplex PCR showed the involvement of capsular serogroups A &D. All the isolates showed the presence of 10 genes for virulence factors. The disease confirmation of both serotypes was proven by Koch's postulates using Swiss albino mice. Further, histopathological brain lesions along with the immunohistochemical detection of bacterial antigens were corroborated with natural cases of P. multocida as described above. To the best of our knowledge, we first time report the neuroinvasion of P. multocida in naturally infected pigs., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A 1-month-old rabbit, imported as a pet by a distributor, died suddenly in the quarantine period in Japan due to suppurative pleuropneumonia. A bacterial isolate from its right lung was identified as Pasteurella multocida serotype A: 11. The isolate was classified as ST204 using the RIRDC scheme of multilocus sequence typing, suggesting that the isolate was genetically related to European isolates of the same sequence type listed in the PubMLST database and not to four other isolates that originated from past imported rabbits. In the immunohistochemical assay, an antiserum recognizing the somatic serotype 11 antigen generated from chicken could specifically detect P. multocida, indicating that the antiserum for somatic serotyping was useful for immunohistochemical diagnosis of rabbit pasteurellosis.

Pasteurella multocida causes a variety of infectious diseases in various species of mammals and birds, resulting in enormous economic loss to the modern livestock and poultry industry. However, the mechanism of host-pathogen interaction is unclear. Here, we found that l-serine levels were significantly decreased in murine lungs infected with P. multocida Exogenous l-serine supplementation significantly increased the survival rate of mice and decreased the colonization of P. multocida in the lungs of mice. Notably, l-serine decreased the macrophage- and neutrophil-mediated inflammatory responses in mice during P. multocida infection., (Copyright © 2019 He et al.)

This study assessed the antimicrobial activity of 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM), a novel pleuromutilin candidate with a substituted pyrimidine moiety, against Pasteurella multocida. Minimum Inhibitory Concentration (MIC), Oxford Cup assay, and time-kill experiments were used to measure the activity of DPTM against P. multocida serotype A in vitro. We observed that DPTM was potent against Pasteurella multocida serotype A with the MIC value of 0.781 μg/mL. The mean inhibition-zone diameters of DPTM (50, 25, and 12.5 μg/mL) were 29.4, 24.2 and 20.1 mm, respectively. Time-kill experiments showed that the drug caused a rapid decline in the number of bacteria compared with the initial inoculum at 4 h and killed 94.6% of the bacteria during 24 h. Furthermore, DPTM activity was also assessed in a lung infection model challenged with 4.0 × 10 9  CFU/mL P. multocida serotype A. The results showed that DPTM significantly reduced mortality rate and bacterial load, and alleviated the pathological changes of lung. The antibacterial effect of DPTM found in this study suggested that it was useful in the prevention or control of pneumonia caused by P. multocida., (Copyright © 2018. Published by Elsevier Ltd.)

The incidence of disease caused by Pasteurella sp. in farmed lumpsuckers in Norway has been steadily increasing in recent years, causing significant economic losses and fish welfare issues. The disease affects all life stages, both in hatcheries and after release into salmon cages. Therefore, it is important to establish robust challenge models, to be used for vaccine development. Exposure experiments via intramuscular and intraperitoneal injection underlined the high virulence of the bacteria, whereas the cohabitation and bath models allowed the chronic symptoms of the disease to be studied more accurately. Skin lesions and haemorrhage at the base of fins were observed in the more acute cases of the disease. Symptoms including white spots over the skin, especially around the eyes, characterized the chronic cases. The latter were most prominent from the bath challenge model. Histopathology indicated a systemic pattern of disease, whereas qPCR analysis from head kidney showed that bacteria may be present in survivor fish at the end of the challenges. In all the challenge models investigated, Pasteurella sp. was re-isolated from the fish, thus fulfilling Koch's postulates. These findings highlight the importance of screening of lumpsuckers prior to transfer to minimize the risks of carrying over asymptomatic carriers., (© 2018 John Wiley & Sons Ltd.)

Fowl cholera is caused by the bacterium Pasteurella multocida and is known to cause significant economic losses in the commercial turkey industry. Four hundred and thirty cases of P. multocida in commercial turkeys, submitted to the California Animal Health and Food Safety Laboratory System (CAHFS) from January 1, 1991, to December 31, 2017, were analyzed. Records examined included CAHFS branch location, date of submission, clinical signs, company and premise of origin, age and sex of submitted turkeys, macroscopic findings, organs in which P. multocida was isolated, and serotype and fingerprint information. Increased mortality as high as 1200 birds per day was the most common complaint at submission, with acute septicemic lesions observed in the majority of cases. The mean age of turkeys diagnosed with fowl cholera was 14 wk, with a median age of 17 wk. Cases most frequently occurred from September to November, with 36% of cases occurring during this time period. Serotyping was performed in 350 cases, while fingerprinting was performed in 171 cases. Serotypes 3 and 3,4 were frequently identified in the 26-yr time period, while the fingerprints identified varied over time. Despite the decreasing population of commercial turkeys in California since the 1990s, fowl cholera continues to be an economically significant disease in this sector.

Pasteurella multocida is one of the most important pathogen that causes pneumonia in swine. Although several virulence factors are known, the pathogenesis of this bacterium is not well-studied. Therefore, to study the pathogenesis of P. multocida infection in porcine lung, next-generation RNA sequencing was used to compare the transcriptomes of P. multocida grown in vivo and in vitro, respectively. After P. multocida infection a total of 704 genes were expressed in vitro, 1422 genes were expressed in vivo, and 237 genes were differentially expressed based on statistical analyses, padj of ≤0.1. Genes encoding ribosomal proteins or other products that function in the regulation of transcription and translation were downregulated, whereas genes whose products affected cellular processes (protein transport and RNA degradation) and metabolic pathways, such as those of amino acid metabolism and nucleotide metabolism, were upregulated in vitro compared with in vivo. This study shows that differentially expressed genes in P. multocida regulate pathways that operate during stress, iron capture, heat shock, and nitrogen regulation. However, extensive investigation of the pathogenic mechanism of P. multocida is still required., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Photobacterium damselae species are one of the most devastating bacterial pathogens in mariculture worldwide. Some species of Photobacterium are pathogenic for marine animals and human. They are the causative agents of photobacteriosis, formerly known as pasteurellosis. A total of (202) marine fishes of three different species were represented as: seabass (Dicentrarchus labrax), seabream (Sparus aurata) and gray mullet (Mugil capitus) randomly collected from Lake Temsah at Ismailia governorate along the parallel Pelagic road to the lake in the governorate from August 2015 to July 2016. The clinical picture and gross lesions of the diseased fishes were recorded. Isolation and identification of suspected bacteria using traditional and molecular methods. Samples from affected organs were collected for studying the histopathological alterations of these pathogens. Fifty one fishes were found to be infected with Photobacterium damselae subsp. Piscicida. Seabass (Dicentrarchus labrax) was the most infected fish species (23), followed by seabream (Sparus aurata) (18) finally gray mullet (Mugil capitus) was (10). 91fishes were found to be infected with P. damselae subsp. damselae, seabass (Dicentrarchus labrax) was the most infected fish sp. (36), followed by seabream (Sparus aurata) (32), then gray mullet (Mugil capitus) (23). The results indicated that, the total prevalence of P. damselae subsp. piscicida in all examined species (25.24%), the highest seasonal prevalence was recorded in summer season (37.09%) followed by autumn (26%) then spring (20.37%) and winter (11.11%). On the other hand, the total prevalence of P. damselae subsp. damselae in all examined species (45.04%), the highest seasonal prevalence was recorded in summer season (67.74%) followed by autumn (52%) then spring (29.62%) and winter (19.44%). Molecular diagnosis with conventional PCR used to confirm the traditional isolation was applied by using specific primers of two genes (polycapsular saccharide gene and urease C gene). The histopathological studies of naturally infected marine fishes showed severe inflammatory reactions in different organs with accumulation of melanomacrophages and necrosis. The results confirm that P. damselae subspecies damsalea is the most prevalent pathogen between marine fishes, and seabass (Dicentrarchus labrax) was the highly affected marine fishes in this study., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The lipopolysaccharide (LPS) produced by the Gram-negative bacterial pathogen Pasteurella multocida has phosphoethanolamine (PEtn) residues attached to lipid A, 3-deoxy-d-manno-octulosonic acid (Kdo), heptose, and galactose. In this report, we show that PEtn is transferred to lipid A by the P. multocida EptA homologue, PetL, and is transferred to galactose by a novel PEtn transferase that is unique to P. multocida called PetG. Transcriptomic analyses indicated that petL expression was positively regulated by the global regulator Fis and negatively regulated by an Hfq-dependent small RNA. Importantly, we have identified a novel PEtn transferase called PetK that is responsible for PEtn addition to the single Kdo molecule (Kdo 1 ), directly linked to lipid A in the P. multocida glycoform A LPS. In vitro assays showed that the presence of a functional petL and petK , and therefore the presence of PEtn on lipid A and Kdo 1 , was essential for resistance to the cationic, antimicrobial peptide cathelicidin-2. The importance of PEtn on Kdo 1 and the identification of the transferase responsible for this addition have not previously been shown. Phylogenetic analysis revealed that PetK is the first representative of a new family of predicted PEtn transferases. The PetK family consists of uncharacterized proteins from a range of Gram-negative bacteria that produce LPS glycoforms with only one Kdo molecule, including pathogenic species within the genera Vibrio , Bordetella , and Haemophilus We predict that many of these bacteria will require the addition of PEtn to Kdo for maximum protection against host antimicrobial peptides., (Copyright © 2017 American Society for Microbiology.)

In September 2012, five Bolivian squirrel monkeys housed in a zoological park died within sequential several days without obvious clinical signs. In a necrospy, one monkey presented swelling of the kidney with multifocal white nodules in the parenchyma, and other two had pulmonary congestion. Histopathologically, multifocal bacterial colonies of gram-negative coccobacillus were found in the sinusoid of the liver in all monkeys examined (Nos.1-4). Additionally, purulent pyelonephritis, pneumonia and disseminated small bacterial colonies in blood vessels were observed. Immunohistochemically, the bacterial colonies from two monkeys were positive for P. multocida capsular serotype D. Based on these findings, these monkeys were diagnosed as septicemia caused by acute P. multocida infection.

Pasteurella multocida serotype F isolates are predominately prevalent in avian hosts, but rarely seen in pigs. However, we isolated several strains of P. multocida serotype F from clinical samples of pigs in China. To understand the pathogenicity of these strains, one of the serotype F isolates designated HN07, was used to challenge experimental chickens, as P. multocida of this serotype is predominately prevalent in avian hosts. However, strain HN07 could not resulted in significant clinical signs in experimental chickens even at an infective dose of ∼10 9 CFU, suggesting the isolate was avirulent to chickens and therefore raising the possibility that the porcine serotype F isolate is not transmitted by chickens. We then used HN07 to challenge experimental pigs, as this strain was isolated from pigs. As expected, the strain led to the clinical signs and the pathological lesions in experimental pigs that are similar to the pasteurellosis disease. We then determined the complete genome sequence of the pig origin serogroup F isolate HN07 for the first time. Genome comparison between HN07 and the avian serotype F P. multocida Pm70 identified a novel integrative conjugative element (ICE) ICEpmcn07 which was likely to harbor a series of genes responsible for a putative type IV secretion system (T4SS) in HN07. This is the first time that we determined an ICE carrying a T4SS in P. multocida. Besides, comparative analysis also defined a number of virulence-associated genes in HN07 but absent in Pm70 which may have a contribution to the pathogenicity of the strain. This is the first report of the pathogenicity and genome characterization of a pig origin Pasteurella multocida serogroup F isolate. The pathogenic and genomic definition of the pig origin P. multocida serogroup F in our study would have significance on the pathogenesis and genetic diversity and virulence variability of P. multocida., (Copyright © 2016. Published by Elsevier B.V.)

We present the first case of a complicated foot infection caused by Fusobacterium russii in Austria. F. russii is highly associated with mammals such as cats and dogs. Our case underlines the difficulties in isolation and identification of anaerobes and the pitfalls in antimicrobial treatment of polymicrobial infections., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The genes encoding OmpA of Pasteurella multocida recovered from diseased and apparently healthy animals have been characterized. The nucleotide sequence revealed ORFs of 1047-1077 bp encoding proteins of 349-360 amino acids. Domain analysis of OmpA showed signal peptide, N-terminal ompA domain and C-terminal ligand binding domain. The transmembrane topology of OmpA showed short turns at the periplasmic end and longer irregular loops at the extracellular end. The phylogenetic analysis based on OmpA showed affiliation of isolates to 7 groups representing different alleles. The identical segments in OmpA also suggested assortative recombination within classes IV, V and VI of distinct lineages. Principal component analysis separated isolates into groups based on capsular type and PmompA alleles. The alleles belonging to class VI exclusively associated with capsular type A, whereas class I-IV were associated with capsular type B. PmompA alleles in class V were recorded in both serogroups. PmompA6.1, 6.4 were distributed among strains with capsular type A, and PmompA6.2 and 6.3 among capsular type B. Despite internal OmpA variabilty, restrictive and well defined distribution was seen amongst P. multocida. A definitive association of "OmpA-capsular type" was observed with clinical status of animals. A cohort of pasteurellae comprising of OmpA(I-IV)-capB was recovered from diseased animals and OmpA(VI)-capA from healthy subjects. This study concludes that P. multocida with serogroup A and B from healthy and diseased animals represent distinct clusters also differentiated based on their OmpA-types and OmpA-capsular type relationship possibly determine the virulence and disease outcome., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The possible interaction between Pasteurella multocida and the mycotoxin fumonisin B1 (FB1), recognised as one of the most often food/feed contaminant, was studied with the aim to evaluate whether and how FB1 can influence and/or complicate the development and severity of various pathological damages provoked by Pasteurella multocida in some internal organs of pigs. Heavier lung pathology was seen in pigs experimentally infected with Pasteurella multocida, when the same were exposed to 20ppm dietary levels of fumonisin B1 (FB1) as was assessed by gross pathology, pathomorphological examinations, clinical biochemistry and some immunological investigations. The most typical damages in FB1 treated pigs were the strong oedema in the lung and the slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological findings in pigs infected with Pasteurella multocida was broncho-interstitial pneumonia. FB1 was found to aggravate pneumonic changes provoked by P. multocida in the cranial lobes of the lung and to complicate pneumonic damages with interstitial oedema in the lung. No macroscopic damages were observed in the pigs infected only with Pasteurella multocida. It can be concluded that the feed intake of FB1 in pigs may complicate or exacerbate the course of P. multocida serotype A infection., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To identify the gram-negative rods grown from blood cultures and a right-knee fluid aspirate from an 80-year-old caucasian man who had undergone a total right knee arthroplastic procedure 6 years ago, and to assess the genetic similarity between the 2 isolates., Methods: We used 3 different approaches: biochemical testing, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, and 16S ribosomal RNA (rRNA) gene sequencing., Results: The 3 methods identified the gram-negative rods as Pasteurella multocida; 16S rRNA gene sequencing further identified the organisms as P. multocida subsp. septica., Conclusion: A concordant identification of P. multocida was observed using biochemical testing, mass spectrometry, and 16S rRNA gene sequencing. Only 16S rRNA sequencing was able to determine the subspecies of P. multocida and to determine the genetic relatedness of the 2 isolates., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Host-pathogen interactions of Pasteurella multocida isolates of different origin were studied in a mouse model, focusing on pathology, bacterial load and expression of the metalloproteinase MMP9 and its inhibitor TIMP1. Intranasal inoculation with one of three doses (10(6), 10(4), 10(2)CFU) of an isolate from porcine pneumonia or fowl cholera showed marked differences between the two isolates. The avian isolate was highly pathogenic with severe signs of necrotizing pneumonia, liver necrosis and high bacterial load in lung and liver. Clinical signs and pathology related to the porcine isolate were dose dependent and consisted of exudative bronchopneumonia, abscess formation in liver and a lower bacterial load in lung and liver. Both isolates caused increased expression of MMP9 and TIMP1. In conclusion, evaluation and comparison of pathogenicity and host-pathogen interaction of P. multocida isolates from different hosts is possible in the intranasal murine model., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Haemorrhagic septicaemia is a disease caused by Pasteurella multocida serotype B: 2 and E: 2. The organism causes acute, highly fatal septicaemic disease with high morbidity and mortality in cattle and more susceptible in buffaloes. Lipopolysaccharide can be found on the outer cell wall of the organism. Lipopolysaccharide is released during multiplication which leads to inflammatory reaction. It represents the endotoxin of P. multocida type B: 2 and responsible for toxicity in haemorrhagic septicaemia which plays an important role in the pathogenesis of the disease. Therefore, the aim of this study was to investigate the clinical signs, blood parameters, gross post mortem lesions and histopathology changes caused by P. multocida type B:2 immunogen lipopolysaccharide infections initiated through intravenous and oral routes of infection. 9 buffalo heifers were divided equally into 3 treatment groups. Group 1 was inoculated orally with 10 ml of phosphate buffer saline (PBS); Group 2 and 3 were inoculated with 10 ml of lipopolysaccharide broth intravenously and orally respectively. For the clinical signs, there were significant differences (p < 0.05) in temperature between the control, intravenous and oral group. In hematology and biochemistry findings, there were significant differences (p < 0.05) in erythrocytes, haemoglobin, PCV, MCV, lymphocytes, monocytes, eosinophils, GGT and albumin between the control, intravenous and oral group. However, there were no significant differences (p > 0.05) in the MCHC, leukocytes, band neutrophils, basophils, thrombocytes, plasma protein, icterus index, total protein, globulin and A:G ratio between intravenous and oral group. For Group 2 buffaloes, there were gross lesions in the lung, trachea, heart, liver, spleen, and kidney. In contrast, lesions were only observed in the lung, trachea and liver of Group 3 buffaloes. There were significant differences (p < 0.05) in hemorrhage and congestion; necrosis and degeneration; and inflammatory cells infiltration between experimental groups and control group. However, there were no significant differences (p > 0.05) in edema lesion between groups. In conclusion, this study is a proof that oral route infection of P. multocida type B:2 immunogen lipopolysaccharide can be used to stimulate host cell responses where oral vaccine through feed could be developed in the near future., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Haemorrhagic septicaemia (HS) is an acute, septicaemic disease of cattle and buffalo of Asia and Africa caused by Pasteurella multocida B:2 or E:2. Buffaloes are believed to be more susceptible than cattle. In this study, 9 buffaloes of 8 months old were divided equally into 3 groups (Groups 1, 3, 5). Similarly, 9 cattle of 8 months old were equally divided into 3 groups (Groups 2, 4, 6). Animals of Groups 1 and 2 were inoculated with PBS while Groups 3 and 4 were inoculated subcutaneously with 10(5) cfu/ml of P. multocida B:2. Animals of Groups 5 and 6 were inoculated intranasally with the same inoculum. Both buffaloes and cattle that were inoculated subcutaneously succumbed to the infection at 16 h and 18 h, respectively. Two buffaloes that were inoculated intranasally (Group 5) succumbed at 68 h while the remaining cattle and buffaloes survived the 72-h study period. Endotoxin was detected in the blood of infected cattle (Group 4) and buffaloes (Groups 3 and 5) prior to the detection of P. multocida B:2 in the blood. The endotoxin was detected in the blood of buffaloes of Group 3 and cattle of Group 4 at 0.5 h post-inoculation while buffaloes of Group 5 and cattle of Group 6 at 1.5 h. On the other hand, bacteraemia was detected at 2.5 h in buffaloes of Group 3 and cattle of Group 4 and at 12 h in buffaloes of Group 5 and cattle of Group 6. Affected cattle and buffaloes showed lesions typical of haemorrhagic septicaemia. These included congestion and haemorrhages in the organs of respiratory, gastrointestinal and urinary tracts with evidence of acute inflammatory reactions. The severity of gross and histopathology lesions in cattle and buffalo calves that succumbed to the infection showed insignificant (p > 0.05) difference. However, inoculated buffalo and cattle that survived the infection showed significantly (p < 0.05) less severe gross and histopathological changes than those that succumbed. In general, cattle are more resistant to intranasal infection by P. multocida B:2 than buffaloes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., Conclusions: Activation of mTOR signalling plays a central role in the formation of osteoclasts through the bacterial toxin PMT. On the molecular level, PMT-induced activation of mTOR leads to down regulation of PDCD4, a known repressor of AP-1 complex, culminating in the activation of c-Jun, an essential transcription factor for triggering osteoclastogenesis.

The increased frequency of isolation of Pasteurella multocida capsular type B from rabbitries in north-western India prompted this investigation into the role of this organism in inducing disease in rabbits. Ten rabbits were divided into two groups of five animals. Group I rabbits were infected intranasally (IN) with 1 ml of inoculum containing 2 × 10(5) colony forming units/ml, while rabbits in group II were given 1 ml phosphate buffered saline IN. The rabbits in group I developed respiratory distress, increased rectal temperature and severe dyspnoea, with death occurring 24-48 h post infection. The main pathological findings were severe congestion and haemorrhage in the trachea, fibrinopurulent pneumonia, bacteraemia and septicaemia. The nasal secretions of all group I animals contained P. multocida. These observations indicate that in addition to P. multocida capsular types A and D, P. multocida capsular type B can also be highly pathogenic for rabbits., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: In humans, Pasteurella multocida infections are usually limited to the soft tissues surrounding a lesion. However, P. multocida can also cause systemic infections (such as pneumonia, lung abscess, peritonitis, endocarditis, meningitis and sepsis)-especially in patients with other underlying medical conditions., Case Presentation: We report on a case of fulminant P. multocida bacteremia at several sites (soft tissues, endocarditis and joints) on a white European man. Despite surgery and intensive medical care, the patient died., Conclusions: The present case emphasizes the importance of appropriate initial treatment of skin wounds. Patients at risk should be aware of the possible consequences of being bitten, scratched or licked by their pet.

Pasteurella multocida is a common commensal of the gastrointestinal and respiratory tracts of animals, especially cats and dogs. It is transmitted to humans through contact with animals. Bite wound infection is the most common clinical manifestation. Systemic infections are unusual and mainly affect immunocompromised individuals. The article presents two cases of Pasteurella infection. Wound infection in a 75-year-old female following a bite from her pet cat was associated with bacteremia. The disease course was favorable with the initial clindamycin treatment despite in vitro resistance. The other patient was a 62-year-old female diagnosed with acute bacterial meningitis with multiple brain abscesses and transient expressive aphasia. She reported frequent contacts with pets and domestic animals without a recent bite. Hematogenous dissemination of the infection was suspected. Because of poor therapeutic response, cefotaxime was switched to chloramphenicol which was later switched to a combination of cefotaxime with ciprofloxacin due to anemia. Following 6 weeks of intravenous antibiotic therapy and another 10 weeks of oral ciprofloxacin therapy, magnetic resonance imaging showed normal results and the neurological defect resolved. Epidemiological, clinical and therapeutic aspects of Pasteurella infection are discussed and literature is reviewed.

We present a case of fulminant Pasteurella multocida sepsis in a 66-year-old man who had undergone a renal transplant. Our patient lived with two dogs and a cat with which he was very close. We propose that his bacteraemia might have resulted from direct inoculation of P multocida via his cat licking the venous stasis ulcers on his legs. The patient's clinical course was complicated by cardiopulmonary failure and he ultimately succumbed to his infection. P multocida is a rare cause of infections in immunocompromised hosts, epidemiologically linked to exposure to cats, dogs, and other animals. This case of P multocida shows the importance of considering this organism in immunocompromised hosts presenting with severe infections, especially if their history shows exposure to domesticated or wild animals known to be potential carriers of this disease. In this Grand Round, we review the clinical features, epidemiology, treatment, and prognosis of P multocida infections with a focus on these features in patients who are immunosuppressed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Context: Acute phase proteins (APPs) are proposed as potential markers of the health status in pigs., Objective: Circulating APPs in pigs co-infected with swine influenza virus and Pasteurella multocida., Methods: Serum APPs were measured in co-infected and control pigs with the use of commercial ELISA tests., Results: All investigated APPs revealed significant changes in co-infected pigs during the study period. The concentration of C-reactive protein, haptoglobin and serum amyloid A (SAA) increased significantly at 2 dpi, before respiratory signs and fever were observed. Concentration of Pig-MAP increased significantly at 3 dpi. C-reactive protein and SAA reaction were rapid but short-lived. The concentration of Hp and Pig-MAP in serum also increased at very early stage of co-infection but remained elevated for a longer period of time., Conclusions: Maximal concentration of serum amyloid A correlated with the disease severity in pigs.

Prepiscibactin (1) is a possible intermediate in the biosynthesis of piscibactin, the siderophore responsible for the iron uptake of the bacterium Photobacterium damselae subsp. piscicida, the aethiological agent of fish pasteurellosis. Compound 1 was synthesized by a convergent approach starting from L-/D-cysteine and 2-hydroxybenzonitrile. The key steps were a highly diastereoselective SmI2-mediated Reformatsky reaction and Zn(2+)-induced asymmetric thiazolidine formation followed by lactamization. The absolute configuration 9R,10S,12R,13S was established for 1, and this confirmed the previous relative stereochemistry proposed on the basis of NOE and computational methods.

Pasteurella multocida serotype A:3 has been mostly implicated in pneumonic pasteurellosis in ruminants. In contrast, our previous studies have reported that both serotypes A:1 and A:3 were responsible for respiratory diseases in cattle and buffaloes. However, the pathology and pathogenesis of P. multocida serotype A:1 (Pm A:1) infection have not been studied in ruminants. In the present study, 12- to 15-week-old buffalo calves (Bubalus bubalis) infected by Pm A:1 had fibrinous and suppurative bronchopneumonia with focal areas of coagulation necrosis typical of pneumonic pasteurellosis. For the first time, this study reports the lung pathology and pathogenecity of Pm A:1 infection in calves., (© The Author(s) 2014.)

Pasteurella multocida is a pathogenic, Gram-negative bacterium that is commonly found as normal flora in nasopharynx of variety of wild and domestic animals. Numerous virulence factors have been described for P. multocida isolates which include adherence and colonization factors, iron-regulated and acquisition proteins, extracellular enzymes such as neuraminidase, lipopolysaccharide (LPS), capsule and a variety of outer membrane proteins (Omp). OmpA has a significant role in stabilizing the cell envelope structure by providing physical linkage between the outer membrane & peptidoglycan. It has been shown to mediate P. multocida -host cells interaction via heparin and/or fibronectin binding and therefore act as an important invasive molecule which could determine the final outcome of initial infection. Comparative nucleotide sequence analysis of ompA gene of P. multocida has revealed that despite extensive genetic diversity in ompA of P. multocida, most sequences could be classified into two major allele classes namely ompA allele (I) and allele (II). The P. multocida recovered from nasal cavity of bovine and belonging to two ompA classes were tested for their differential virulence. In vitro pathogenicity studies on Madin Darby Bovine Kidney (MDBK) cell line employing adhesion and invasion assays indicated that P. multocida strain with ompA (I) is more invasive than P. multocida strain with ompA (II). In vivo studies in mice further reiterated that the isolates harbouring ompA(I) were comparatively more virulent to isolates harbouring ompA (II).

Abstract: A female American kestrel (Falco spaverius) fledgling was found on the ground with a suspected trauma to the right eye and open-mouth breathing. During the first 2 days of hospitalization, the bird developed severe bilateral periorbital cellulitis, blepharoedema, and sinusitis. The periocular tissues of the right globe were devitalized and communicated with a fistula at the commissure of the right side of the beak. The blepharoedema of the left eye was aspirated and yielded a dark colored malodorous fluid, which was submitted for aerobic bacterial and Mycoplasma cultures. Results showed a mixed infection with Mycoplasma buteonis, Avibacterium gallinarum, and Staphylococcus pasteuri, all of which are not commonly isolated from birds of prey. With antimicrobial therapy, supportive care, and surgical debridement of the right periocular necrotic tissues and adhesed phthisical globe, the kestrel recovered from this severe mixed upper respiratory infection.

Fowl cholera, caused by Pasteurella multocida, remains a major problem of poultry worldwide. In the current report, we describe an outbreak in free range organic broilers. In addition to culturing samples from dead broilers, we attempted to isolate P. multocida from feral cats trapped on the farm. The isolates were identified by PCR as P. multocida and then serotyped using the Heddleston scheme and genotyped using both a multilocus sequence typing (MLST) method and an enterobacterial repetitive intergenic consensus (ERIC)-PCR method. A total of 123 isolates of P. multocida were recovered from 12 broilers. All 123 isolates were examined by ERIC-PCR, and only one pattern was identified. A subset of seven broiler isolates were examined by MLST and all were typed as sequence type (ST) 20. A total of 28 isolates of P. multocida were recovered from 17 cats, and five ERIC-PCR genotypes were identified, with one genotype (E-1, shared by 19 isolates) being the same as the ERIC-PCR pattern associated with the broilers. One representative cat strain for each ERIC-PCR pattern was subjected to MLST. The cat isolate with the same ERIC-PCR genotype as the broiler isolates was confirmed as having the same MLST result, ST 20. The other five cat ERIC-PCR patterns were allocated to four STs: E-2 and E-5 to ST 265, E-3 to ST 30, E-4 to ST 20, and E-6 to ST 264. Both genotyping methods confirmed that isolates of P. multocida were common between the feral cats and the chickens. It was not clear whether the strain was transmitted from the cats to the chicken or whether the cats obtained the strain preying on chicken. The study has shown that cats can harbor P. multocida strains with the same genotype found in chickens affected with fowl cholera.

Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Recently, rifaximin, a non-absorbable antibiotic which is used to prevent recurrent hepatic encephalopathy, has been proposed as effective prophylaxis for SBP. Here, we present an unusual case of SBP under treatment with rifaximin. A 50-year-old woman with liver cirrhosis was admitted because of tense ascites and abdominal pain. She was under long-term oral prophylaxis with rifaximin due to hepatic encephalopathy. Paracentesis revealed SBP caused by Pasteurella multocida, which was sensitive to multiple antibiotics, including rifaximin. Treatment with ceftriaxone resulted in rapid resolution of the peritonitis and restoration of the patient. Since P. multocida is usually transmitted from pets, the patient's cat was tested and could be identified as the most likely source of infection. This case should elicit our awareness that uncommon pathogens and unusual routes of transmission may lead to SBP, despite antibacterial prophylaxis with non-absorbable antibiotics. Nevertheless, such infections may still remain sensitive to systemic therapy with conventional antibiotics.

Pasteurella multocida is a common pathogen of swine that causes specific diseases with great economic impact. However, the importance of this pathogen in wild boar is still unknown. In the current work, an outbreak of systemic pasteurellosis in wild boar with a high mortality rate is described. A total of 23 wild boar of all ages were found dead over a 5-day period on a game estate in southwest Spain (11.11% mortality). Three animals were necropsied and showed subcutaneous edema, a generalized congestion, and fibrin deposits in the peritoneal cavity. Hemorrhages, general congestion, and intravascular thrombosis were microscopically observed. Pasteurella multocida type B was isolated from all of the studied organs. Outbreaks of systemic pasteurellosis have been described in domestic pigs from Asia and Australia, but not to date in Europe. This outbreak suggests that systemic pasteurellosis affecting wild boar populations may be an important cause of mortality.

Infectious bronchopneumonia is a widespread disease in modern commercial pig production and Pasteurella multocida is frequently associated with the lesions. To evaluate porcine lung lesions associated with P. multocida, populations of inflammatory cells were examined by immunohistochemistry in necrotic lung lesions from nine pigs and exudative lung lesions from eleven pigs. Lungs from five pigs served as controls. All cases were selected from naturally infected pigs using co-infection based criteria to make them as comparable as possible. The inflammatory cells demonstrated by immunohistochemistry were T-lymphocytes (CD3(+), CD4(+) and CD8(+) subsets), B-lymphocytes, neutrophils, macrophages, and IgA(+), IgM(+) and IgG(+) cells. The results showed that (1) a significant increase in all inflammatory cells was found in lesions associated with P. multocida, (2) necrotic lesions had a larger number of CD3(+) T-lymphocytes and IgA(+) cells, and (3) cases with exudative lesions had a more CD8(+) T-lymphocytes, B-lymphocytes, macrophages and neutrophils. No differences in the numbers of CD4(+) T-lymphocytes, IgG(+) and IgM(+) positive cells were found between necrotic and exudative cases. The results show that P. multocida significantly alters the inflammatory response in the lung and that lesions associated with P. multocida display diverse inflammatory responses according to their distinct morphological pattern., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The gram-negative bacterium Pasteurella multocida causes pneumonic and systemic pasteurellosis in bovids for which vaccines are either unavailable or inadequate. The work assessed whether an intranasal P. multocida challenge in mice might provide a model of infection for future vaccine development work. Clinical, pathological and biochemical responses were compared in seven strains of mice challenged with a virulent bovine pneumonic isolate of P. multocida A:3. Six mouse strains (Porton, CD-1, BALB/c, VM, C57BL/10 and C57BL/6) developed clinical signs of pneumonic disease and variable pneumonic lesions 41-70 h post-infection. In contrast, mouse strain RIII became septicaemic within 36 h post-infection. Concentrations of plasma acute phase proteins and serum lipopolysaccharide increased in all mice after infection, and the main or interaction effect of mouse strain and infection status was statistically significant (P<0.05). Responses in C57BL/10 mice showed close similarity to bovine pneumonic and in RIII mice to bovine systemic pasteurellosis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The ability of recombinant outer membrane proteins of Pasteurella pneumotropica to vaccinate against the infections of mice was studied. The proteins examined were the homologues of the P4, P6, P26, and D15 proteins of Haemophilus influenzae. Intranasal vaccination with P4 and P6 produced protection against pneumonia. P6 vaccination, which was most studied, reduced the peak bacteria load in lungs by 50-fold and caused a rapid resolution of an infection that lasted for at least 5 days in unvaccinated animals. Protection could be partially transferred with CD4(+) T cells and pulmonary challenge with the P6 antigen induced interferon-γ and the Th17 cytokine IL-21. This is the first demonstration of the ability of a recombinant P6 to mediate protective immunity to a pathogen in its natural host and it is proposed that it would not only have utility for mouse breeding but also for investigating how to improve the efficacy of vaccination with homologous proteins for related species., (Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The present study was conducted to study the protective effect of ethanolic extract of propolis given subcutaneously (S/C) either alone or in combination with inactivated formalized Pasteurella multocida (P. multocida) vaccine in rabbits challenged with virulent P. multocida strain. Twenty-eight New-Zealand rabbits, 6-8 weeks old and not vaccinated against pasteurellosis, were randomly divided into four equal groups. Group (1) was kept as nonvaccinated control. Group (2) was injected S/C with propolis. Group (3) was vaccinated (S/C) with P. multocida vaccine only. Group (4) was injected with vaccine mixed with propolis as adjuvant. Groups (2, 3, and 4) received the same doses of propolis and vaccine after 4 weeks as a booster dose. The experiment continued for six weeks during which clinical signs, body weight, and mortality rate were recorded. Blood samples were collected every 2 weeks of treatment for evaluating the erythrogram and biochemical parameters. At the end of six weeks, all groups were subjected to challenge with a virulent strain of P. multocida. Two weeks later, tissue specimens were collected from different organs for histopathological investigation. Results showed that before challenge all rabbits of different groups were apparently healthy and had good appetite. After challenge, control group (1) showed acute form of the disease, 100% mortality rate, and severe histopathological changes. Rabbits of groups (2 and 3) showed less severe clinical signs, mortality rate, and histopathological changes than control. Rabbits of group (4) were apparently healthy with normal histological picture. In conclusion, an ethanolic extract of propolis injected alone or combined with formalized inactivated P. multocida vaccine improved general health conditions, liver and kidney functions in addition to reduction of the severity of adverse clinical signs, mortality rates, and histopathological changes associated with challenge of rabbits with P. multocida strain.

The 146-kDa Pasteurella multocida toxin (PMT) is the main virulence factor to induce P. multocida-associated progressive atrophic rhinitis in various animals. PMT leads to a destruction of nasal turbinate bones implicating an effect of the toxin on osteoblasts and/or osteoclasts. The toxin induces constitutive activation of Gα proteins of the G(q/11)-, G₁₂/₁₃- and G(i)-family by deamidating an essential glutamine residue. To study the PMT effect on bone cells, we used primary osteoblasts derived from rat calvariae and stromal ST-2 cells as differentiation model. As marker of functional osteoblasts the expression and activity of alkaline phosphatase, formation of mineralization nodules or expression of specific transcription factors as osterix was determined. Here, we show that the toxin inhibits differentiation and/or function of osteoblasts by activation of Gα(q/11). Subsequently, Gα(q/11) activates RhoA via p63RhoGEF, which specifically interacts with Gα(q/11) but not with other G proteins like Gα₁₂/₁₃ and Gα(i). Activated RhoA transactivates the mitogen-activated protein (MAP) kinase cascade via Rho kinase, involving Ras, MEK and ERK, resulting in inhibition of osteoblast differentiation. PMT-induced inhibition of differentiation was selective for the osteoblast lineage as adipocyte-like differentiation of ST-2 cells was not hampered. The present work provides novel insights, how the bacterial toxin PMT can control osteoblastic development by activating heterotrimeric G proteins of the Gα(q/11)-family and is a molecular pathogenetic basis for understanding the role of the toxin in bone loss during progressive atrophic rhinitis induced by Pasteurella multocida.

Pasteurella species are part of the oral flora of cats and dogs. In humans, they are frequently found in infected animal bite wounds, but invasive infections are rare. This is the first report of prosthetic-valve endocarditis with a Pasteurella dagmatis-like species, which originated from the patient's cat.

We report a tubo-ovarian abscess due to Pasteurella multocida. This zoonotic infection was likely of ascending origin, as Pasteurella was also isolated from vaginal swabs.

The first complete genome sequence of the P. multocida avian isolate Pm70 was reported in 2001. Analysis of the genome identified many predicted virulence genes, including two encoding homologues of the Bordetella pertussis filamentous haemagluttinins, and genes involved in iron transport and metabolism. Availability of the genome sequence allowed for a range of whole-genome transcriptomic and proteomic analyses and these have helped us understand how P. multocida responds to growth in the presence of antibiotics, under low iron conditions and in the host. Unfortunately, no new P. multocida genome sequences were determined during the rest of the decade, limiting any possible comparative genomic analyses until recently, when several new genome sequences have become available. Here we use the available data to identify a number of important similarities and differences between the strains and determine their phylogenetic relationships. Interestingly, based on the current data there is no clear correlation between phylogenetic relatedness and host predilection or disease.