Pasteurella haemolytica A1 and Bovine Respiratory Disease: Pathogenesis

Abstract

The severe fibrinonecrotic pneumonia associated with pneumonic pasteurellosis usually results from colonization of the lower respiratory tract by Pusteurellu huemolyticu biotype A, serotype l(A1). Despite recent research efforts, the authors lack a detailed understanding of the interactions and host response to P. huemolyticu in the respiratory tract. The authors hypothesize that management and environmental stress factors or viral infection alters the upper respiratory tract (URT) epithelium allowing P. huemolyticu to colonize the epithelium. Once the URT is colonized, large numbers of organisms enter the lung where they interact with alveolar macrophages. Endotoxin, released from the bacteria, crosses the alveolar wall where it activates pulmonary intravascular macrophages, endothelium, neutrophils, lymphocytes, platelets, complement, and Hageman factor leading to complex interactions of cells and mediators. It is the progression of this inflammatory response with neutrophil influx that is ultimately responsible for the pulmonary injury. Leukotoxin is a major virulence factor of P. haemolyiicu that allows it to survive by destroying phagocytic cells. At subcytolytic concentrations it may also enhance the inflammatory response by activating cells to produce mediators and release reactive oxygen metabolites and proteases. has been reproduced experimentally in calves by transthoracic or intratracheal administration of P. huemolytica A 1 alone.*.'* Despite recent research efforts, we lack a detailed understanding of the interaction and host response to P.huernolyticu A1 in the ruminant respiratory tract. This article reviews the information presently available on the interaction of this bacteria with the respiratory tract and discusses possible pathogenic mechanisms. We will not attempt to review the extensive literature on viral-bacterial synergism as it relates to pulmonary bacterial infections. In addition, we will not discuss the effect of stress on immune function and its effect on the susceptibility of cattle to shipping fever. However, the reader is referred to several articles on these s~bjects.~,~~~*'~-'' Several observations point to the central role that P. haemolyticu A1 has in bovine shipping fever. In clinically healthy cattle, P. huemolyticu are present in low numbers in the nasal passages and those that are isolated are predominantly biotype A serotype 2 (A2) which is rarely associated with shipping Exposure of healthy cattle to stressful agents such as viral infection, change in management practices (marketing, transportation and processing), and change in environmental (heat, cold) conditions, leads to an explosive growth and selective colonization by P. huemolyticu A1 in the upper

Pharmacokinetics and Distribution of Florfenicol in Bronchial Secretions of Healthy and Pasteurella multocida Infected Calves

“…The development of clinical signs (pyrexia, tachyponea, anorexia), hematological changes (leucocytosis, neutophilia) and bacteriological findings were very similar to those reported in clinical cases of "shipping fever" [5,30]. The principle method for treating pneumonic pasteurellosis is antibiotic therapy [31]. Florfenicol has been suggested as an appropriate antimicrobial drug for the treatment of respiratory disease in cattle [15,27], the suggestion which is supported by the results of the present study.…”

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

“…These factors allow M. haemolytica to escape or exceed clearance and host defences, to proliferate in the lung and to cytolyse alveolar macrophages and neutrophils, which further enhances the lung injuries [31,91,183].…”

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

“…The disease is a cause of considerable economic loss to the beef and dairy cattle industries of North America [56]. The bacterium produces a variety of virulence factors [8], of these a large body of evidence indicates that the leukotoxin (LktA) and lipopolysaccharide (LPS) play a significant role in the pathogenesis that lead to the lung 772 P. Thumbikat et al pathology characteristic of the disease [59].…”