Chapter 23 The Genera Mannheimia and Pasteurella
Mannheimia and Pasteurella are members of the class α-Proteobacteria, order Pasteurellales, family Pasteurellaceae, that contain small, facultatively anaerobic, nonmotile, gram-negative rods or coccobacilli that do not form endospores. Glucose is fermented without gas production, the oxidase reaction is normally positive, and nitrate is usually reduced to nitrite. These organisms are found as mucosal commensals of the oropharynx and gastrointestinal tract of healthy mammals, birds, and reptiles. They survive poorly outside the host.
THE GENUS MANNHEIMIA
The new genus Mannheimia was established in 1999 to include trehalose-negative members of the Pasteurella haemolytica complex. All strains in the genus ferment mannitol, and failure to fermentD-mannose is a key by which Mannheimia spp. are differentiated from members of the genus Pasteurella. The five current species in the genus Mannheimia are Mannheimia haemolytica, Mannheimia granulomatis, Mannheimia glucosida, Mannheimia ruminalis, and Mannheimia varigena (Table 23-1).
TABLE 23-1 Hosts and Significance of Mannheimia Species
| Species | Host(s) | Significance |
|---|---|---|
| M. haemolytica | Cattle | Pneumonia |
| Sheep | Pneumonia, septicemia, mastitis | |
| M. granulomatis | Cattle | Panniculitis (lechiguana) |
| Deer and hares | Bronchopneumonia, conjunctivitis | |
| M. glucosida | Sheep | Normal respiratory flora |
| M. ruminalis | Cattle, sheep | Normal ruminal flora |
| M. varigena | Pigs | Septicemia, enteritis, pneumonia |
| Cattle | Septicemia, pneumonia, mastitis |
Mannheimia haemolytica was historically classified into 17 serotypes based on indirect hemagglutination of capsular surface antigens. The organism was further divided into two biotypesA and T, based on the ability to ferment the sugars L-arabinose or trehalose, respectively. T biotype strains (serotypes 3, 4, 10, and 15) have recently been reclassified as a separate species, Pasteurella trehalosi. Serotype A11 is now M. glucosida, and the A biotype strains A1, A2, A5-A9, A12-A14, A16, and A17 remain as M. haemolytica.
DISEASE AND EPIDEMIOLOGY
Mannheimia haemolytica is one of the most important pathogens of domestic cattle. It is the primary bacterial agent responsible for bovine pneumonic pasteurellosis, also known as “shipping fever,” because of its frequent occurrence in transported animals. It is a major cause of morbidity and mortality, accounting for approximately 30% of the total cattle deaths globally. A recent study estimated the annual economic loss to the U.S. beef cattle industry at $640 million.
Historically, serotype A1 has been the predominant strain associated with pneumonic pasteurellosis. Results of a recent U.S. survey reaffirmed that fact, indicating that serotype A1 accounted for approximately 60% of the total isolates recovered from pneumonic bovine lungs, whereas serotype 6 was isolated from 26% and serotype 2 from 7%. The remaining 7% was composed of serotype 9, 11, or untypable strains.
Bovine respiratory disease is multifactorial, involving environmental factors and concurrent infections with viruses (infectious bovine rhinotracheitis, bovine viral diarrhea, parainfluenza 3, or bovine respiratory syncytial) and other bacterial agents (mycoplasmas, Pasteurella multocida, or Histophilus somni).
Mannheimia haemolytica is usually an innocuous inhabitant of the nasal cavity and tonsillar crypts. However, when calves are stressed by overcrowding, exhaustion, starvation, dehydration, or cold temperatures, they become more susceptible to illness. Organisms shed from the nasal cavity serve as a source of infection for other animals. Infections are spread by inhalation of bacteria-containing droplets, by direct nose-to-nose contact, or by ingestion of feed contaminated with nasal discharges from infected cattle. The two most important factors in determining if an exposed animal will develop pneumonia are the challenge dose of M. haemolytica and the immune status of the host.
Clinical signs of shipping fever, including depression, anorexia, fever, nasal discharge, and a soft, moist cough, become apparent 6 to 10 days after a stressful episode. When lung consolidation becomes extensive, dyspnea and open-mouth breathing often develop. Mortality is high because of bronchial obstruction with fibrinous exudates. Survivors have irreversible lung damage and a high relapse rate and remain lifelong chronic poor-doers.
Mannheimia haemolytica may also cause septicemia in young lambs, acute or chronic pneumonia in sheep, and an uncommon but severe mastitis in ewes.
Experimental and epidemiologic evidence supports a role for M. granulomatis, interacting with Dermatobia hominis, in the etiology of lechiguana in Brazilian cattle. The disease is characterized by large, hard, subcutaneous swellings that progress rapidly and cause the death of untreated animals after a 3- to 11-month clinical course. Microscopic lesions consist of focal proliferation of fibrous tissue, and infiltration with plasma cells, eosinophils, lymphocytes, and occasionally neutrophils. The primary lesion is an eosinophilic lymphangitis, which results in eosinophilic abscesses, with occasional rosettes containing bacteria in their centers.
Mannheimia varigena strains have been isolated from sporadic cases of bovine mastitis, calf pneumonia, and septicemia, as well as from the oral cavity and gastrointestinal tract of healthy animals. Bovine mastitis is thought to be trauma associated, perhaps from overvigorous suckling of calves or from poor milking equipment. Disease may be severe, with high fever, marked udder edema, and agalactia. Fibrosis and atrophy of affected quarters or entire udders may result in culling of an animal from the milking herd. If calves are allowed to suckle infected cows, pneumonia or septicemia may result. Mannheimia varigena is apparently a normal resident of the upper respiratory tract of healthy pigs, but has also been isolated from pigs with pneumonia or enteritis.
PATHOGENESIS
Study of pathogenesis of Mannheimia spp. infections has mainly addressed disease caused by M. haemolytica. Field evidence suggests that viral and mycoplasmal agents predispose the animal to pneumonic pasteurellosis by impairing normal host defenses and that synergy between these agents and M. haemolytica is usually responsible for natural outbreaks of bovine respiratory disease. When animals are stressed, rapid, selective proliferation of serotype A1 occurs in the nasopharynx. Organisms reaching the lungs infect alveolar epithelium, and invasion of the lower respiratory tract is associated with rapid deterioration of lung architecture and function. Within hours of infection, the bronchi, bronchioles, and alveoli are infiltrated by neutrophils, fibrin, blood, and seroproteinaceous fluid. Pulmonary damage is a direct result of action of bacterial products, as well as leukocyte- and platelet-mediated injury, the end result of which is acute fibrinous pleuropneumonia.
The primary virulence factors are leukotoxin and lipopolysaccharide (LPS). Leukotoxin, a pore-forming cytotoxin of the RTX family, induces lysis of ruminant leukocytes and platelets, but not those from other species. It impairspulmonary macrophage function and bacterial clearance and damages lung parenchyma through the release of proteolytic enzymes from lysed leukocytes. Decreased antigen-presenting capacity of macrophages aids in lung colonization, directly impairing induced pulmonary defenses.
Pulmonary exposure to LPS induces hemorrhage, edema, hypoxemia, and acute inflammation, and is an important contributor to maintenance and extension of lesions caused by M. haemolytica pulmonary infections. Macrophage activation by LPS (and leukotoxin) induces release of proinflammatory cytokines. There is apparent synergy between leukotoxin and LPS in diminution of alveolar macrophage function and increased inflammatory cytokine expression.
Other virulence determinants of M. haemolytica include capsular polysaccharide, iron-regulated proteins, enzymes, and fimbriae (Table 23-2). Antibodies against a carbohydrate surface component of M. haemolytica may also protect against M. haemolytica infection, suggesting a role in virulence for this yet-to-be characterized factor.
TABLE 23-2 Virulence Factors of Mannheimia haemolytica
| Virulence Factor | Activity |
|---|---|
| Leukotoxin | Pore-forming cytolysin, lethal for leukocytes and platelets; impairment of pulmonary macrophage function |
| Lipopolysaccharide | Stimulates production of proinflammatory cytokines, lipid mediators, procoagulant substances, oxygen radicals, proteases that damage lung parenchyma |
| Capsular polysaccharide | Adherence to lower respiratory mucosa, inhibits phagocytosis, mediates resistance to complement-mediated lysis, neutrophil chemoattractant |
| Fimbriae | Adherence |
| Siderophore | Iron acquisition |
| O-sialoglycoprotein endopeptidase | Cleaves glycoproteins, inactivates macrophages and other leukocytes |
| Neuraminidase | Reduces viscosity of respiratory mucus, impairs mucociliary blanket, allows bacterial penetration to respiratory epithelium |
DIAGNOSIS
Diagnosis is based on bacterial isolation from clinical specimens. Mannheimia spp. grow readily on blood agar or glucose agar plates supplemented with serum. Colonial morphology is similar forall species; colonies are smooth, grayish, variablyβ-hemolytic, and 1 to 2 mm in diameter after24 hours’ incubation (Figure 23-1). Species are differentiated on the basis of phenotype (Table 23-3).
PREVENTION AND CONTROL
Treatment, prevention, and control of bovine pneumonic pasteurellosis involve management, vaccination, and supportive therapy. Stress and crowding should be avoided. “Preconditioning” calves before shipping, which includes vaccination against common viral respiratory pathogens at least 3 weeks before shipping and not commingling animals from different sources, has been advocated. Early disease recognition, isolation of clinically ill animals, and prompt antimicrobial therapy should be instituted.
A commercial vaccine containing leukotoxoid and surface antigens protects against pneumonic pasteurellosis. Commercial bacterins are, in general, inefficacious and may actually exacerbate disease. Vaccination with bacterins induces formationof opsonizing antibodies that facilitate phagocytosis, leading to increased phagocytic cell lysis andsubsequent severe pulmonary inflammation. Antiinflammatory agents may be useful, and anti-microbials (macrolides, penicillins, cephalosporins, or florfenicol) are usually administered to prevent further bacterial multiplication and secondary infection. Plasmid-mediated resistance in some strains may be a significant problem.
