Application of the MISTEACHING(S) disease susceptibility framework to Actinobacillus pleuropneumoniae to identify research gaps: an exemplar of a veterinary pathogen

Abstract

Historically, the MISTEACHING (microbiome, immunity, sex, temperature, environment, age, chance, history, inoculum, nutrition, genetics) framework to describe the outcome of host−pathogen interaction, has been applied to human pathogens. Here, we show, using Actinobacillus pleuropneumoniae as an exemplar, that the MISTEACHING framework can be applied to a strict veterinary pathogen, enabling the identification of major research gaps, the formulation of hypotheses whose study will lead to a greater understanding of pathogenic mechanisms, and/or improved prevention/therapeutic measures. We also suggest that the MISTEACHING framework should be extended with the inclusion of a ‘strain’ category, to become MISTEACHINGS. We conclude that the MISTEACHINGS framework can be applied to veterinary pathogens, whether they be bacteria, fungi, viruses, or parasites, and hope to stimulate others to use it to identify research gaps and to formulate hypotheses worthy of study with their own pathogens.

JMM Profile: Actinobacillus pleuropneumoniae: a major cause of lung disease in pigs but difficult to control and eradicate

“…Pleuropneumonia can occur in pigs of all ages [ 3 ]. An extensive review of host and microbial factors that underly susceptibility of pigs to A. pleuropneumoniae infection has recently been published [ 15 ].…”

Comparative Efficacy in Challenge Dose Models of a Toxin Expressing Whole-Cell Vaccine against Eight Serovars of Actinobacillus pleuropneumoniae in Pigs

“…The peracute and acute forms are easily diagnosed due to the evident and distinct clinical signs and appearance of dead pigs. Also, the chronic form, likely to develop from any form of pleuropneumonia, is easily diagnosed via slaughterhouse investigations [ 1 , 2 , 3 , 4 ]. Depending on the quality of the on-farm monitoring of animals, the far less distinct clinical signs and low fatality of the subacute form are easily missed and erroneously considered as subclinical; interpreted as “no pleuropneumonic issues”.…”

“…In reality there are likely 18 serovars, as serovars 9 and 11 can be considered as one: serovar 9/11, as the difference in the complete capsule polysaccharide loci is only one amino acid and they have identical toxin profiles (ApxI, ApxII) [ 35 ]. Different serovars are considered to have quite variable inherited virulence partly due to different Apx-toxin profiles [ 2 , 29 , 30 , 31 , 36 , 37 ].…”

“…A. pleuropneumoniae has several virulence factors, some are well described, and several are under investigation. The three exotoxins: ApxI-III and lipopolysaccharide (LPS) are of major importance both in the development of lung lesions and protective immunity [ 2 , 37 , 38 ]; ApxI, II, and III are, together, the antigens considered capable of inducing cross-protection [ 1 , 2 , 3 , 37 , 39 ]. Many other virulence factors have been described [ 37 , 39 ], including membrane proteins, some of which are immunogenic and therefore can add to the vaccine protective capacity [ 40 ].…”

“…Modified live vaccines are currently under investigation on an experimental basis only. Their potential as commercial vaccines need further investigation [ 2 ]. Several commercial vaccines are available which differ in their composition and can be classified broadly into one of three categories: (1) killed A. pleuropneumoniae whole-cell components only (bacterins, including autogenous vaccines); (2) subunit vaccines containing ApxI-III toxins only; and (3) a combination of these [ 40 ].…”