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Mannheimia (M.) haemolytica (formerly Pasteurella [P.] haemolytica) is the primary aetiological agent of pneumonic pasteurellosis--one of the most important respiratory diseases in cattle and sheep. While bovine pneumonic pasteurellosis is regarded to be mainly caused by M. haemolytica serotype A1, and in Germany during the last years also by serotype A6, sheep can be infected by all serotypes although there is an increased prevalence of serotypes A2 and A5-7. The obligate pathogenicity of M. haemolytica is proven by isolation of pure cultures from pneumonic lungs as well as by infection studies. Knowledge about the virulence mechanisms of M. haemolytica and their molecular basis are fragmentary, most probably due to the complex gene regulation of virulence associated factors in lung tissues. This review summarizes the current literature covering virulence factors to substantiate a model of pathogenesis. After serotype A1 strains have colonized the bovine upper respiratory tract they replace other serotypes by mechanisms unknown to date. After fulminant proliferation in the upper respiratory tract the microorganisms colonize the lower respiratory tract, finally entering alveolar spaces. An inflammatory cascade is initiated by M. haemolytica LPS and Leukotoxin, causing activation of the complement system and release of cytokines. Pathognomonic for bovine pneumonic pasteurellosis is the strong influx of neutrophiles accompanied by accumulation of fibrin, finally causing necrosis of alveolar spaces. Depending on lesion size this fibronecrotizing pneumonia can result in death of the animals. In addition, possible protective antigens are discussed. There is still a great effort in the development of efficacious vaccines against pneumonic pasteurellosis in cattle and sheep caused by various M. haemolytica serotypes worldwide. The scarce knowledge concerning presence and distribution of virulence associated factors in M. haemolytica strains and their role in pathogenesis made it difficult to determine a suitable vaccine candidate in the past. In addition, there is lack of knowledge concerning the variability of virulence factors in individual isolates. Genome sequence analysis of M. haemolytica, enabling proteomics and transciptomics, hopefully will give new insight into the pathogenesis of pneumonic pasteurellosis.

In the examined strains the production of following toxins or enzymes was determined by bioassay or by semiquantitative and routine diagnostical tests: delta-endotoxin, alpha-exotoxin, beta-exotoxin hemolysin, phospholipase C, proteinase. The production of delta-endotoxin (= a parasporal crystal toxic for several insects) is the only character in that B. thuringiensis differs from B. cereus. Other biochemical features as production of so-called alpha-exotoxin (= soluble toxic protein), hemolysin, phospholipase or proteinase are common in both species. Strains of B. megaterium may produce proteinase, but no phospholipase, hemolysin or alpha-exotoxin. The identity of the alpha-exotoxin of the B. cereus-thuringiensis group with any of the exoenzymes studied here could not be confirmed. At present, this toxin is only demonstrable by bioassay. Formation of beta-exotoxin (= soluble toxic nucleotide) is restricted to special strains of the B. cereus-thuringiensis group. -- All strains of B. megaterium tested do not produce any of the toxins quoted; they have found to be apathogenic under the experimental conditions. As the so-called "egg yolk clearing factor" is produced by all strains of B. megaterium (in contrast to strains of the B. cereus-thuringiensis group) it does not represent a factor of pathogenicity and therefore the term "gamma-exotoxin" is unfounded. -- Not too much attention should be paid in connection with taxonomic studies to the ability or non-ability of strains of bacteria to produce a special toxin.

Isolation of bacteria from a field of bean plants (Phaseolus vulgaris L.) with conspicuous symptoms of halo blight disease resulted in 123 bacterial strains from which 57 were identified as Pseudomonas syringae pv. phaseolicola . At 18 degrees C the phaseolotoxin production of the isolated strains differs widely in submerse culture. Only few strains produce high amounts of phaseolotoxin being comparable with those of the reference strain 1321, while most of the strains show a low capability of phaseolotoxin production. Furthermore, we proved the stability of phaseolotoxin production of 29 strains. After one year about 50% of the strains were extremely reduced in their capability of phaseolotoxin production. We found that the reason for this reduction of toxin production is the appearance of Tox- segregants within a Tox+ clone. At 24 degrees C all strains (with one exception) show considerable lower amounts of toxin production or none at all: maximally 30% of the toxin amounts synthesized at 18 degrees C were produced. At 28 degrees C none of the isolated strains produce phaseolotoxin . The present data allow the conclusion to be drawn that in natural environments there exists a wide spread regarding the amount and stability of the phaseolotoxin production.