Mannheimia haemolytica growth and leukotoxin production for vaccine manufacturing — A bioprocess review

TobiasOppermann, NadineBusse, PeterCzermak

Fraunhofer Institute for Molecular Biology and Applied Ecology, Project Group Bioresources, Winchesterstrasse 2, 35394 Giessen, Germany.

Abstract

Mannheimia haemolytica leukotoxin (LKT) is a known cause of bovine respiratory disease (BRD) which results in severe economic losses in the cattle industry (up to USD 1 billion per year in the USA). Vaccines based on LKT offer the most promising measure to contain BRD outbreaks and are already commercially available. However, insufficient LKT yields, predominantly reflecting a lack of knowledge about the LKT expression process, remain a significant engineering problem and further bioprocess optimization is required to increase process efficiency. Most previous investigations have focused on LKT activity and cell growth, but neither of these parameters defines reliable criteria for the improvement of LKT yields. In this article, we review the most important process conditions and operational parameters (temperature, pH, substrate concentration, dissolved oxygen level, medium composition and the presence of metabolites) from a bioprocess engineering perspective, in order to maximize LKT yields.

Keywords: Bovine respiratory disease, Cell growth, Commensal flora of cattle, Enzootic calf pneumonia, Facultatively anaerobic, Gram-negative, Leukotoxin production, Mastitis in sheep, Operational parameters, Mannheimia haemolytica, Rod-shaped bacteria.