Actinobacillus pleuropneumoniae (App, previously Haemophilus pleuropneumoniae), is a Gram-negative, facultative anaerobic, respiratory pathogen found in pigs. It was first reported in 1957, and was formally declared to be the causative agent of porcine pleuropneumonia in 1964. It was reclassified in 1983 after DNA studies showed that it was more closely related to Actinobacillus lignieresii.
A. pleuropneumoniae is a non-motile, Gram-negative, encapsulated coccobacillus bacteria found in the Pasteurellaceae family. It exhibits β-hemolysis activity, thus explaining its growth on chocolate or blood agar, but must be supplemented with NAD ('V factor') in order to facilitate growth for one of its biological variants (biovar 1). As a facultative anaerobic pathogen, A. pleuropneumoniae may need CO2 in order to grow. Depending on the biovar, the bacteria may or may not be positive for urease; both biovars are positive for porphyrin.
A. pleuropneumoniae was found to be the causative agent for up to 20% of all bacteria pneumonia cases in swine. The main disease associated with this bacterium is porcine pleuropneumonia, a highly contagious respiratory disease, affecting primarily young pigs (usually less than 6 months). All of the symptoms and signs of porcine pleuropneumonia can be attributed to its virulence factors. The symptoms include respiratory distress, bloodstained discharge (usually frothy) from the mouth, fever, anorexia, mild diarrhea, cyanosis, lethargy and spontaneous abortion in sows. The most common sign for a pig farmer is the sudden death of several pigs over a short period of time. Peak mortality is usually reached when pigs are 10–16 weeks old. It is not uncommon for mortality rates to reach 20-80% in fattening pigs, with similarly high morbidity. Pigs that do survive the disease will remain carriers and spread the bacterium to other swine. Several bacterial combinations are seen in vivo; the most common simultaneous infection being Pasteurella multocida. Treatment must be immediate and continuous. Antibiotics used include ceftiofur, tetracycline, synthetic penicillins, tylosin and sulfonamides.
15 different serotype variants (serovars) have been recognized for Actinobacillus pleuropneumoniae, based on the different capsular polysaccharides exhibited. Two different biovars exist, with biovar 1 having 13 different serovars and biovar 2 having 2 serovars. Differences in virulence potential, immunogenicity and worldwide geographical distribution contribute to the diversity of the A. pleuropneumoniae serotypes. All 15 serotypes can cause disease, with one serotype usually predominating in a particular herd. The main difference between the serotypes is the expression of Apx toxins and other virulence factors.
The bacterium rapidly colonizes the host and attaches to the epithelial cells of the tonsils, moving down to the respiratory tract utilizing type IV fimbriae. As the bacteria replicate, they release cytotoxins (in the form of Apx toxins), hemolysins and the LPS on their outer membranes. The subsequent lysis of macrophages causes a release of lysozymes, which in turn cause the tissue damage seen in porcine pleuropneumonia. As stated by Auger et al., members of the Pasteurellaceae family routinely change the cellular processes of the infected cell. In particular, A. pleuropneumoniae activates the creation of various cytokines such as interleukin 1β (IL-1β), IL-8 and tumor necrosis factor-alpha (TNF-α). IL-8 is itself a chemical signal used to attract neutrophils to the infection site.
The typical presentation of A. pleuropneumoniae in pigs is the characteristic demarcated lesions in the middle, cranial and caudal lobes of the lung. Areas of severe pneumonic growth are dark and consolidated. In the case of chronically infected pigs, pleural adhesions and abscesses are normally found. Histological studies of infected lung tissue will normally showcase lung necrosis, neutrophil infiltration, macrophage and platelet activation and an exudate. Severe hemolysis or hemorrhaging is also present.
Several virulence factors account for the remarkable pathogenesis of Actinobacillus pleuropneumoniae. The more important ones include the production and release of the Apx toxins, the ability to produce a biofilm, its LPS layer, capsule polysaccharides and its ability to survive within an iron-limited environment. Out of these, the most important are its capsule and Apx toxin production.
The Apx toxin, a member of the RTX toxin family, is subdivided into four types: ApxI through ApxIV. As a pore-forming exotoxin, Apx toxin lyses alveolar epithelial cells, endothelial cells, red blood cells, neutrophils and macrophages. Each serotype expresses different amounts of the four Apx toxins. The most virulent combination known to exist, ApxI and ApxII, is expressed by serovars 1, 5, 9, and 11. The ApxII and ApxIII combination is of medium virulence and is expressed by serovars 2, 3, 4, 6, 8, and 15.
The bacteria are usually spread through direct nose-to-nose contact. It is species specific, as its Apx toxin only affects pigs and other swine. Overcrowding in pigpens, co-infections of other respiratory pathogens, and unusual stress all contribute to the spread of the disease. A. pleuropneumoniae must have a host to survive, and will not survive for a significant amount of time outside a host. This bacterium is found worldwide, with different serotypes prevailing in different locations. Serotypes 1, 3, 5 and 7 are most commonly found in North America.
Actinobacillus pleuropneumoniae has a profound economic impact on pork production and pig farmers. In 1995, A. pleuropneumoniae infections cost the US economy approximately $30 million. Such losses usually result from medication and veterinary expenses, increased mortality of pigs, extra labor and other factors.
- "Actinobacillus pleuropneumoniae". Iowa State University College of Veterinary Medicine. Retrieved 20 April 2013.
- Shope, RE (1964). "Porcine Contagious Pleuropnemonia: 1. Experimental Transmission, Etiology, and Pathology". Journal of Experimental Medicine 119 (3): 357–368. doi:10.1084/jem.119.3.357.
- Marsteller, TA; Fenwick B (1999). "Actinobacillus pleuropneumoniae disease and serology". Swine Health and Production 7 (4): 161–165.
- Brownfield, B. "Actinobacillus pleuropneumoniae in swine". Purdue University-Animal Disease Diagnostic Laboratory. Retrieved 20 April 2013.
- Xu, Z; Chen X; Li L; et al. (2010). "Comparative Genomic Characterization of Actinobacillus pleuropneumoniae". Journal of Bacteriology 192 (21): 5625–5636. doi:10.1128/JB.00535-10. PMC 2953695. PMID 20802045.
- Gillaspy, A. "Actinobacillus pleuropneumoniae". Laboratory for Molecular Biology and Cytometry Research-University of Oklahoma Health Sciences Center. Retrieved 20 April 2013.
- Dee, S. "Pleuropneumonia in Pigs". Merck Veterinary Manual. Retrieved 20 April 2013.
- Klitgaard, K; Friis C; Angen O; et al. (2010). "Comparative profiling of the transcriptional response to iron restriction in six serotypes of Actinobacillus pleuropneumoniae with different virulence potential". BMC Genomics 11: 698. doi:10.1186/1471-2164-11-698.
- Chiers, K; De Waele T; Masmans F; et al. (2010). "Virulence factors of Actinobacillus pleuropneumoniae involved in colonization, persistence and induction of lesions in its porcine host". Veterinary Research 41 (65): 65. doi:10.1051/vetres/2010037.
- Auger, E; Deslandes V; Ramjeet M; et al. (2009). "Host-pathogen interactions of Actinobacillus pleuropneumoniae with porcine lung and tracheal epithelial cells". Infection and Immunity 77 (4): 1426–1441. doi:10.1128/IAI.00297-08. PMC 2663157. PMID 19139196.
- Vanden Bergh, PGAC; Zecchinon LM; Fett T; et al. (2009). "Porcine CD18 mediates Actinobacillus pleuropneumoniae ApxIII species-specific toxicity". Veterinary Research 40 (33): 33. doi:10.1051/vetres/2009016.
- Losinger, WC (2005). "Economic impacts of reduced pork production associated with the diagnosis of Actinobacillus pleuropneumoniae on grower/finisher swine operations in the United States". Preventive Veterinary Medicine 68 (2–4): 181–193. doi:10.1016/j.prevetmed.2004.12.004. PMID 15820115.