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Microbiology and Molecular Biology... Nov 2019is a highly versatile pathogen capable of causing infections in a wide range of domestic and wild animals as well as in humans and nonhuman primates. Despite over... (Review)
Review
is a highly versatile pathogen capable of causing infections in a wide range of domestic and wild animals as well as in humans and nonhuman primates. Despite over 135 years of research, the molecular basis for the myriad manifestations of pathogenesis and the determinants of phylogeny remain poorly defined. The current availability of multiple genome sequences now makes it possible to delve into the underlying genetic mechanisms of fitness and virulence. Using whole-genome sequences, the genotypes, including the capsular genotypes, lipopolysaccharide (LPS) genotypes, and multilocus sequence types, as well as virulence factor-encoding genes of isolates from different clinical presentations can be characterized rapidly and accurately. Putative genetic factors that contribute to virulence, fitness, host specificity, and disease predilection can also be identified through comparative genome analysis of different isolates. However, although some knowledge about genotypes, fitness, and pathogenesis has been gained from the recent whole-genome sequencing and comparative analysis studies of , there is still a long way to go before we fully understand the pathogenic mechanisms of this important zoonotic pathogen. The quality of several available genome sequences is low, as they are assemblies with relatively low coverage, and genomes of isolates from some uncommon host species are still limited or lacking. Here, we review recent advances, as well as continuing knowledge gaps, in our understanding of determinants contributing to virulence, fitness, host specificity, disease predilection, and phylogeny of .
Topics: Animals; Genetic Variation; Genome, Bacterial; Genomics; Genotype; Host Specificity; Humans; Pasteurella Infections; Pasteurella multocida; Phylogeny; Virulence; Virulence Factors
PubMed: 31484691
DOI: 10.1128/MMBR.00014-19 -
PloS One 2021Pasteurella multocida is a bacterial pathogen with the ability to infect a multitude of hosts including humans, companion animals, livestock, and wildlife. This study...
Pasteurella multocida is a bacterial pathogen with the ability to infect a multitude of hosts including humans, companion animals, livestock, and wildlife. This study used bioinformatic approaches to explore the genomic diversity of 656 P. multocida isolates and epidemiological associations between host factors and specific genotypes. Isolates included in this study originated from a variety of hosts, including poultry, cattle, swine, rabbits, rodents, and humans, from five different continents. Multi-locus sequence typing identified 69 different sequence types. In-silico methodology for determining capsular serogroup was developed, validated, and applied to all genome sequences, whereby capsular serogroups A, B, D, and F were found. Whole genome phylogeny was constructed from 237,670 core single nucleotide variants (SNVs) and demonstrated an overall lack of host or capsular serogroup specificity, with the exception of isolates from bovine sources. Specific SNVs within the srlB gene were identified in P. multocida subsp. septica genomes, representing specific mutations that may be useful for differentiating one of the three known subspecies. Significant associations were identified between capsular serogroup and virulence factors, including capsular serogroup A and OmpH1, OmpH3, PlpE, and PfhB1; capsular serogroup B and HgbA and PtfA; and capsular serogroup F and PtfA and PlpP. Various mobile genetic elements were identified including those similar to ICEPmu1, ICEhin1056, and IncQ1 plasmids, all of which harbored multiple antimicrobial resistance-encoding genes. Additional analyses were performed on a subset of 99 isolates obtained from turkeys during fowl cholera outbreaks from a single company which revealed that multiple strains of P. multocida were circulating during the outbreak, instead of a single, highly virulent clone. This study further demonstrates the extensive genomic diversity of P. multocida, provides epidemiological context to the various genotyping schemes that have traditionally been used for differentiating isolates, and introduces additional tools for P. multocida molecular typing.
Topics: Animals; Bacterial Outer Membrane Proteins; DNA Transposable Elements; Drug Resistance, Bacterial; Genes, Bacterial; Pasteurella Infections; Pasteurella multocida; Polymorphism, Single Nucleotide; Poultry Diseases; Serogroup; Turkeys; Virulence Factors
PubMed: 33822782
DOI: 10.1371/journal.pone.0249138 -
BMC Veterinary Research Nov 2022Pasteurella multocida (P. multocida) infection can cause a series of diseases in different animals and cause huge economic losses to the breeding industry. P. multocida...
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.
Topics: Animals; Rabbits; Pasteurella multocida; Virulence; Lagomorpha; Pasteurella Infections; Immunity, Innate; Cytokines
PubMed: 36447208
DOI: 10.1186/s12917-022-03517-9 -
International Journal of Medical... May 2020Pasteurella 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... (Review)
Review
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.
Topics: Adaptation, Physiological; Animals; Evolution, Molecular; Genetic Variation; Genome, Bacterial; Genomics; Humans; Interspersed Repetitive Sequences; Pasteurella Infections; Pasteurella multocida; Phylogeny; Polymorphism, Single Nucleotide; Poultry; Virulence
PubMed: 32276876
DOI: 10.1016/j.ijmm.2020.151417 -
Toxins Aug 2017is a heterogeneous species that is a primary pathogen of many different vertebrates. This Gram-negative bacterium can cause a range of diseases, including fowl cholera... (Review)
Review
is a heterogeneous species that is a primary pathogen of many different vertebrates. This Gram-negative bacterium can cause a range of diseases, including fowl cholera in birds, haemorrhagic septicaemia in ungulates, atrophic rhinitis in swine, and lower respiratory tract infections in cattle and pigs. One of the primary virulence factors of is lipopolysaccharide (LPS). Recent work has shown that this crucial surface molecule shows significant structural variability across different strains, with many producing LPS structures that are highly similar to the carbohydrate component of host glycoproteins. It is likely that this LPS mimicry of host molecules plays a major role in the survival of in certain host niches. LPS also plays a significant role in resisting the action of chicken cathelicidins, and is a strong stimulator of host immune responses. The inflammatory response to the endotoxic lipid A component is a major contributor to the pathogenesis of certain infections. Recent work has shown that vaccines containing killed bacteria give protection only against other strains with identical, or nearly identical, surface LPS structures. Conversely, live attenuated vaccines give protection that is broadly protective, and their efficacy is independent of LPS structure.
Topics: Animals; Bacterial Vaccines; Chickens; Lipopolysaccharides; Pasteurella multocida
PubMed: 28825691
DOI: 10.3390/toxins9080254 -
Veterinary Research Nov 2021QseC, a histidine sensor kinase of the QseBC two-component system, acts as a global regulator of bacterial stress resistance, biofilm formation, and virulence. The...
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 in Pasteurella multocida. We found that deleting qseC in P. multocida serotype A:L3 significantly down-regulated bacterial virulence. The mutant had significantly reduced capsule production but increased resistance to oxidative stress and osmotic pressure. Deleting qseC led to a significant increase in qseB expression. Transcriptome sequencing analysis showed that 1245 genes were regulated by qseC, 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 including ompA, ptfA, plpB, vacJ, and sodA. In addition to presenting strong immune protection against P. multocida serotypes A:L1 and A:L3 infection, live ΔqseC also exhibited protection against P. multocida serotype B:L2 and serotype F:L3 infection in a mouse model. The results indicate that QseC regulates capsular production and virulence in P. multocida. Furthermore, the qseC mutant can be used as an attenuated vaccine against P. multocida strains of multiple serotypes.
Topics: Animals; Mice; Pasteurella Infections; Pasteurella multocida; Virulence
PubMed: 34801081
DOI: 10.1186/s13567-021-01009-6 -
Glycobiology Oct 2023Pasteurella multocida, an encapsulated gram-negative bacterium, is a significant veterinary pathogen. The P. multocida is classified into 5 serogroups (A, B, D, E, and...
Pasteurella multocida, an encapsulated gram-negative bacterium, is a significant veterinary pathogen. The P. multocida is classified into 5 serogroups (A, B, D, E, and F) based on the bacterial capsular polysaccharide (CPS), which is important for virulence. Serogroups B and E are the primary causative agents of bovine hemorrhagic septicemia that is associated with significant yearly losses of livestock worldwide, primarily in low- and middle-income countries. The P. multocida disease is currently managed by whole-cell vaccination, albeit with limited efficacy. CPS is an attractive antigen target for an improved vaccine: CPS-based vaccines have proven highly effective against human bacterial diseases and could provide longer-term protection against P. multocida. The recently elucidated CPS repeat units of serogroups B and E both comprise a N-acetyl-β-D-mannosaminuronic acid/N-acetyl-β-D-glucosamine disaccharide backbone with β-D-fructofuranose (Fruf) side chain, but differ in their glycosidic linkages, and a glycine (Gly) side chain in serogroup B. Interestingly, the Haemophilus influenzae types e and d CPS have the same backbone residues. Here, comparative modeling of P. multocida serogroups B and E and H. influenzae types e and d CPS identifies a significant impact of small structural differences on both the chain conformation and the exposed potential antibody-binding epitopes (Ep). Further, Fruf and/or Gly side chains shield the immunogenic amino-sugar CPS backbone-a possible common strategy for immune evasion in both P. multocida and H. influenzae. As the lack of common epitopes suggests limited potential for cross-reactivity, a bivalent CPS-based vaccine may be necessary to provide adequate protection against P. multocida types B and E.
Topics: Animals; Cattle; Humans; Pasteurella multocida; Pasteurella Infections; Polysaccharides; Vaccines; Epitopes
PubMed: 37334939
DOI: 10.1093/glycob/cwad049 -
BMC Veterinary Research Jul 2022Pasteurella multocida is one of the most significant pathogens for a number of animals. In rabbits, the infection is generally associated with the P. multocida...
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.
Topics: Animals; Genomics; Pasteurella Infections; Pasteurella multocida; Rabbits; Serogroup; Virulence
PubMed: 35869529
DOI: 10.1186/s12917-022-03381-7 -
Veterinary Research Mar 2022Pasteurella multocida infection frequently causes fowl cholera outbreaks, leading to huge economic losses to the poultry industry worldwide. This study developed a novel...
Pasteurella multocida infection frequently causes fowl cholera outbreaks, leading to huge economic losses to the poultry industry worldwide. This study developed a novel live attenuated P. multocida vaccine strain for ducks named PMZ2 with deletion of the gatA gene and first four bases of the hptE gene, both of which are required for the synthesis of the lipopolysaccharide (LPS) outer core. PMZ2 produced a truncated LPS phenotype and was highly attenuated in ducks with a > 10-fold higher LD than the wild-type strain. PMZ2 colonized the blood and organs, including the spleen, liver and lung, at remarkably reduced levels, and its high dose of oral infection did not cause adverse effects on body temperatures and body weights in ducks. To evaluate the vaccine efficacy of the mutant, ducklings were inoculated orally or intranasally with PMZ2 or PBS twice and subsequently subjected to a lethal challenge. Compared with the PBS control, PMZ2 immunization stimulated significantly elevated serum IgG, bile IgA and tracheal IgA responses, especially after the boost immunization in both the oral and intranasal groups, and the induced serum had significant bactericidal effects against the wild-type strain. Furthermore, the two PMZ2 immunization groups exhibited alleviated tissue lesions and significantly decreased bacterial loads in the blood and organs compared with the PBS group post-challenge. All the ducks in the PMZ2 oral and intranasal groups survived the challenge, while 70% of ducks in the PBS group succumbed to the challenge. Thus, the P. multocida mutant with mutation of the gatA gene and part of the hptE gene proved to be an effective live attenuated vaccine candidate for prevention of fowl cholera in ducks.
Topics: Animals; Bacterial Vaccines; Ducks; Lipopolysaccharides; Pasteurella Infections; Pasteurella multocida; Poultry Diseases
PubMed: 35236414
DOI: 10.1186/s13567-022-01035-y -
BMC Microbiology Mar 2021Bacteriophages play important roles in the evolution of bacteria and in the emergence of new pathogenic strains by mediating the horizontal transfer of virulence genes....
BACKGROUND
Bacteriophages play important roles in the evolution of bacteria and in the emergence of new pathogenic strains by mediating the horizontal transfer of virulence genes. Pasteurella multocida is responsible for different disease syndromes in a wide range of domesticated animal species. However, very little is known about the influence of bacteriophages on disease pathogenesis in this species.
RESULTS
Temperate bacteriophage diversity was assessed in 47 P. multocida isolates of avian (9), bovine (8), ovine (10) and porcine (20) origin. Induction of phage particles with mitomycin C identified a diverse range of morphological types representing both Siphoviridae and Myoviridae family-types in 29 isolates. Phage of both morphological types were identified in three isolates indicating that a single bacterial host may harbour multiple prophages. DNA was isolated from bacteriophages recovered from 18 P. multocida isolates and its characterization by restriction endonuclease (RE) analysis identified 10 different RE types. Phage of identical RE types were identified in certain closely-related strains but phage having different RE types were present in other closely-related isolates suggesting possible recent acquisition. The host range of the induced phage particles was explored using plaque assay but only 11 (38%) phage lysates produced signs of infection in a panel of indicator strains comprising all 47 isolates. Notably, the majority (9/11) of phage lysates which caused infection originated from two groups of phylogenetically unrelated ovine and porcine strains that uniquely possessed the toxA gene.
CONCLUSIONS
Pasteurella multocida possesses a wide range of Siphoviridae- and Myoviridae-type bacteriophages which likely play key roles in the evolution and virulence of this pathogen.
Topics: Animals; Bacteriophages; Biodiversity; Birds; Cattle; Molecular Typing; Pasteurella multocida; Sheep; Swine
PubMed: 33784980
DOI: 10.1186/s12866-021-02155-9