Leukotoxin of Bibersteinia trehalosi Contains a Unique Neutralizing Epitope, and a Non-Neutralizing Epitope Shared with Mannheimia haemolytica Leukotoxin

Abstract

Bibersteinia trehalosi and Mannheimia haemolytica, originally classified as Pasteurella haemolytica biotype T and biotype A, respectively, under Genus Pasteurella has now been placed under two different Genera, Bibersteinia and Mannheimia, based on DNA-DNA hybridization and 16S RNA studies. While M. haemolytica has been the predominant pathogen of pneumonia in ruminants, B. trehalosi is emerging as an important pathogen of ruminant pneumonia. Leukotoxin is the critical virulence factor of these two pathogens. While the leukotoxin of M. haemolytica has been well studied, the characterization of B. trehalosi leukotoxin has lagged behind. As the first step towards addressing this problem, we developed monoclonal antibodies (mAbs) against B. trehalosi leukotoxin and used them to characterize the leukotoxin epitopes. Two mAbs that recognized sequential epitopes on the leukotoxin were developed. One of them, AM113, neutralized B. trehalosi leukotoxin while the other, AM321, did not. The mAb AM113 revealed the existence of a neutralizing epitope on B. trehalosi leukotoxin that is not present on M. haemolytica leukotoxin. A previously developed mAb, MM601, revealed the presence of a neutralizing epitope on M. haemolytica leukotoxin that is not present on B. trehalosi leukotoxin. The mAb AM321 recognized a non-neutralizing epitope shared by the leukotoxins of B. trehalosi and M. haemolytica. The mAb AM113 should pave the way for mapping the leukotoxin-neutralizing epitope on B. trehalosi leukotoxin and the development of subunit vaccines and/or virus-vectored vaccines against this economically important respiratory pathogen of ruminants.

Acute fibrinous pleuropneumonia and septicaemia caused byBibersteinia trehalosiin neonatal calves in New Zealand

“…Although there are phylogenetic differences between B. trehalosi and Mannheimia haemolytica (separate genus and species), they share certain virulence factors such as lipopolysaccharide and leukotoxin (Bowersock et al 2014;Hanthorn et al 2014;Murugananthan et al 2018). Consequently, the use of vaccines containing Mannheimia haemolytica with high concentrations of leukotoxoid and cell wall antigen has shown cross-protection (Cortese et al 2012;Bowersock et al 2014).…”

Whole-Genome Sequence of Multidrug-Resistant Bibersteinia trehalosi Strain OADDL-BT1

“…Several virulence factors have been identified in B. trehalosi, including fimbriae, polysaccharide capsule, and lipopolysaccharide (5), as well as a leukotoxin, which is considered to be a major virulence factor (6, 7). In addition to virulence factors, increasing antimicrobial resistance has been reported in bacterial respiratory pathogens (8).…”

Leukotoxins

“…While the leukotoxin of M. haemoltica has been well studied, characterization of B. trehalosi leukotoxin has lagged. By developing monoclonal antibodies against B. trehalosi leukotoxin, Murugananthan et al, [7] report that B. trehalosi leukotoxin contains a unique neutralizing epitope and a non-neutralizing epitope shared with M. haemolytica leukotoxin.…”