Construction of an isogenic leukotoxin deletion mutant ofPasteurella haemolyticaserotype 1: characterization and virulence

Tatum, Fred M.; Briggs, R. E.; Sreevatsan, Srinand; Zehr, Emile S; Hsuan, Shih-Ling; Whiteley, Laurence O.; Ames, Trevor R.; Maheswaran, S. K.

doi:10.1006/mpat.1997.0181

Cited by 79 publications

(67 citation statements)

References 24 publications

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“…Indeed, inactivation of M. haemolytica leukotoxin by a gene knockout hardly causes any further pulmonary lesions although the wild-type and mutant strains were equally capable of colonising the upper respiratory tracts of the calves [165]. Moreover, necrosis of neutrophils can be reproduced in vitro with purified LKT [5,34,40,46,88,89,161,162,176].…”

Section: The Main Virulence Weaponmentioning

confidence: 99%

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

2005

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-Mannheimia haemolytica induced pneumonias are only observed in goats, sheep and cattle. The bacterium produces several virulence factors,whose principal ones are lipopolysaccharide and leukotoxin. The latter is cytotoxic only for ruminant leukocytes, a phenomenon that is correlated with its ability to bind and interact with the ruminant β2-integrin Lymphocyte Function-associated Antigen 1. This paper globally reviews all the information available on host-pathogen interactions underlying respiratory mannheimiosis (formerly pasteurellosis), from the stable and the Petri dish to the biochemical cascade of events triggered by the leukotoxin inside ruminant leukocytes. One conclusion can be made: the most widespread cattle respiratory disease with the most important impact on beef production worldwide, is probably due to a tiny ruminant-specific focal variation in the CD18-and/or CD11a-expressing genes.

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Section: The Main Virulence Weaponmentioning

confidence: 99%

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

2005

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“…At sublytic concentrations, LktA activates bovine leukocytes and generates a myriad of inflammatory mediators [4,7,10,11,13,17,36,37,44,45,58]. The significance of LktA as a determinant of pathogenicity has been established in calf models with the use of genetically engineered isogenic leukotoxin deletion mutants of M. haemolytica [50].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Mannheimia (Pasteurella) haemolytica leukotoxin interaction with bovine alveolar macrophage β2 integrins

et al. 2005

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-Mannheimia (Pasteurella) haemolytica, the etiologic agent of bovine pneumonic mannheimiosis, produces an exotoxic leukotoxin. The leukotoxin (LktA) is a member of the RTX (repeats in toxin) family of bacterial cytolysins and is distinguished from other toxins by its unique target cell specificity to ruminant leukocytes occurring through binding to a specific receptor. We have demonstrated previously that the β 2 integrin LFA-1 is a receptor for LktA in bovine leukocytes and is involved in leukotoxin-induced biological effects. However the subunits within LFA-1 involved in binding to LktA, and post-binding signaling leading to cellular activation have not been well characterized. The purpose of our study was to pinpoint these precise subunits on bovine alveolar macrophages and to characterize their interaction with LktA. The results in this study indicate that although LktA can efficiently bind to the CD18 subunit of both LFA-1 and Mac-1, post-binding signaling events including elevation of intracellular calcium and CD18 tail phosphorylation are only observed through LFA-1. Furthermore, LktA also binds to the CD11a subunit of LFA-1. LktA binding to CD11a could be inhibited by a small molecule inhibitor of the I(inserted)-domain, the major ligand binding interface on CD11a. I-domain inhibition significantly blunts LktA-induced intracellular calcium elevation and tyrosine phosphorylation of the CD18 tail. Based on our results we suggest that LFA-1 serves as the functional leukotoxin receptor on bovine alveolar macrophages.Mannheimia haemolytica leukotoxin / receptor / lymphocyte function associated antigen-1 / signaling

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“…69,76 LKT-A is a key virulence factor that contributes to the pathogenesis of inflammation and pulmonary necrosis in SF, and it is specific for ruminant leukocytes. 54,117 In diseased lungs, LKT is associated with the cell membranes of degenerating inflammatory cells located in alveoli. 124 Although most strains of M haemolytica from cattle and sheep produce LKT, not all strains are equally pathogenic, because LKT from these strains do not exhibit similar leukotoxic activity and the amount of LKT produced is variable.…”

mentioning

confidence: 99%

“…36,103,104 The importance of LKT in causing pulmonary necrosis was established by intratracheal inoculation of calves with a LKT-deficient mutant M haemolytica, which caused lower mortality and decreased lung lesions, as compared to animals challenged with the parent strain capable of producing LKT-A. 54,117 M haemolytica-induced pneumonia and other diseases are observed in only ruminants-including cattle, sheep, bighorn sheep, goats, bison, and exotic ruminants-because LKTinduced effects are specific for ruminant macrophages, lymphocytes, neutrophils, and platelets. 34,35 This species specificity stems from the selective interaction of LKT with the b 2 integrin LFA-1 (lymphocyte function-associated antigen 1; CD11a/CD18) on target host cells.…”

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confidence: 99%

Mannheimia haemolytica

2010

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Mannheimia haemolytica serotype S1 is considered the predominant cause of bovine pneumonic pasteurellosis, or shipping fever. Various virulence factors allow M haemolytica to colonize the lungs and establish infection. These virulence factors include leukotoxin (LKT), lipopolysaccharide, adhesins, capsule, outer membrane proteins, and various proteases. The effects of LKT are species specific for ruminants, which stem from its unique interaction with the bovine b2 integrin receptor present on leukocytes. At low concentration, LKT can activate bovine leukocytes to undergo respiratory burst and degranulation and stimulate cytokine release from macrophages and histamine release from mast cells. At higher concentration, LKT induces formation of transmembrane pores and subsequent oncotic cell necrosis. The interaction of LKT with leukocytes is followed by activation of these leukocytes to undergo oxidative burst and release proinflammatory cytokines such as interleukins 1, 6, and 8 and tumor necrosis factor a. Tumor necrosis factor a and other proinflammatory cytokines contribute to the accumulation of leukocytes in the lung. Formation of transmembrane pores and subsequent cytolysis of activated leukocytes possibly cause leakage of products of respiratory burst and other inflammatory mediators into the surrounding pulmonary parenchyma and so give rise to fibrinous and necrotizing lobar pneumonia. The effects of LKT are enhanced by lipopolysaccharide, which is associated with the release of proinflammatory cytokines from the leukocytes, activation of complement and coagulation cascade, and cell cytolysis. Similarly, adhesins, capsule, outer membrane proteins, and proteases assist in pulmonary colonization, evasion of immune response, and establishment of the infection. This review focuses on the roles of these virulence factors in the pathogenesis of shipping fever.

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Construction of an isogenic leukotoxin deletion mutant ofPasteurella haemolyticaserotype 1: characterization and virulence

Cited by 79 publications

References 24 publications

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

Characterization of Mannheimia (Pasteurella) haemolytica leukotoxin interaction with bovine alveolar macrophage β2 integrins

Mannheimia haemolytica

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