Castellani & Chalmers, 1919
Pasteurellaceae comprise a large and diverse family of Gram-negative Proteobacteria with members ranging from important pathogens such as Haemophilus influenzae to commensals of the animal and human mucosa. Most members live as commensals on mucosal surfaces of birds and mammals, especially in the upper respiratory tract. The family includes several pathogens of vertebrates, most notably H. influenzae. This species causes several diseases in humans (though not flu, as was originally thought). Other Pasteurellaceae cause gingivitis and chancroid in humans and many others are important veterinary pathogens.
Pasteurellaceae are typically rod-shaped, and are a notable group of facultative anaerobes. They can be distinguished from the related Enterobacteriaceae by the presence of oxidase, and from most other similar bacteria by the absence of flagella.
Bacteria in the family Pasteurellaceae have been classified into a number of genera based on metabolic properties, but these classifications are not generally accurate reflections of the evolutionary relationships between different species. H. influenzae was the first organism to have its genome sequenced and has been studied intensively by genetic and molecular methodologies. Since 1995, the family has been expanded from three genera to the current thirteen through the use of new genetic-based classification and identification technologies. Many members of the Pasteurellaceae family make excellent natural models for the study of bacterial pathogenesis and host-pathogen-interactions thus giving valuable insights into related human diseases.
Taxonomy and biodiversity
The family Pasteurellaceae includes 38 properly classified species in addition to 24 misclassified species. The majority of taxa have been isolated from disease conditions in warm blooded animals and in particular in farm animals. These bacteria are obligate parasites or commensals of vertebrates, colonizing mainly the mucosal surfaces of the upper respiratory tract, oropharynx, and reproductive tracts and possibly also parts of the intestinal tract. Most taxa represent potential pathogens. Both systemic and local infections have been reported for most taxa involved in diseases. However, pneumonia has been reported most frequently. Fossil remnants of members of Pasteurellaceae have never been reported and information on the diversification of taxa within the family can only be obtained by phylogenetic reconstruction. For more information see Christensen et al.
Comparative analyses of Pasteurellaceae genomes have identified large numbers (>20) of conserved signature indels (CSIs) in different important proteins that are uniquely shared by all sequenced Pasteurellaceae species/strains, but are not found in any other bacteria. Based upon many other conserved indels that are specific for subgroups of Pasteurellaceae species, it has been proposed to divide the family Pasteurellaceae into at least two clades . One proposed clade includes Aggregatibacter, Pasteurella, Actinobacillus succinogenes, Haemophilus influenzae, Haemophilus somnus and Mannheimia succiniciproducens; while the other includes Actinobacillus minor, Actinobacillus pleuropneumoniae, Haemophilus ducryi, Haemophilus parasuis and Mannheimia haemolytica.
RTX toxins are bacterial pore forming toxins that are particularly abundant among pathogenic species of Pasteurellaceae where they play a major role in virulence. RTX toxins of several primary pathogens of the family of Pasteurellaceae are directly involved in causing necrotic lesions of the target organs. Many RTX toxins are mainly known as haemolysins due to their capacity to lyse erythrocytes (red blood cells) in vitro, an effect that seems to be non-specific. It is now known for many RTX toxins that their specific targets are leukocytes, where RTX toxins bind to the corresponding β subunit (CD18) of β2 integrons and then cause a cytotoxic effect. For several RTX toxins the binding to CD18 was shown to be host specific and seems to be the basis determining the host range of a given RTX toxin. Observations on very closely related species of the Pasteurellaceae family with different RTX toxins indicate that these latter contribute to a significant part to the host specificity of the pathogen itself. RTX toxins induce a strong immunologic response generating neutralizing antibodies. They therefore constitute important antigens in modern subunit vaccines.
Outer membrane (OM) proteins for iron acquisition have roles in infection and pathogenesis and have growing appeal as novel targets for anti-infectives and therapeutics. Characterization of cell surface proteins of members of the Pasteurellaceae family including Haemophilus, Actinobacillus, Pasteurella, and the Mannheimia genera of organisms has highlighted several redundant iron acquisition receptors for transferrin, siderophores, and heme/heme-containing proteins. In addition, the identification of several immunogenic lipoproteins and OM proteins has driven research for an effective cross-protective vaccine for these organisms.
DNA sequence data are available for the following Pasteurellaceae members: Aggregatibacter actinomycetemcomitans strain HK1651, Actinobacillus pleuropneumoniae strains L20 and sv1 4074, [Haemophilus] ducreyi strain 35000HP, Haemophilus influenzae strains 86-028NP, R2846, R2866, and Rd, Histophilus somni strains 129Pt and 2336, Mannheimia haemolytica A1 strain ATCC BAA-410, Mannheimia succiniciproducens strain MBEL55E, and Pasteurella multocida strain Pm70.