''Actinobacillus pleuropneumoniae'' (previously ''Haemophilus pleuropneumoniae''), is a

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

facultative anaerobic A facultative anaerobic organism is an organism that makes ATP by aerobic respiration if oxygen is present, but is capable of switching to fermentation if oxygen is absent. Some examples of facultatively anaerobic bacteria are '' Staphylococc ...

, respiratory

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

found in

pig The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous, domesticated, even-toed, hoofed mammal. It is variously considered a subspecies of ''Sus s ...

s. It was first reported in 1957, and was formally declared to be the causative agent of

porcine The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous, domesticated, even-toed, hoofed mammal. It is variously considered a subspecies of ''Sus s ...

pleuropneumonia in 1964. It was reclassified in 1983 after DNA studies showed it was more closely related to ''A. lignieresii''.

Microbiology

''Actinobacillus pleuropneumoniae'' is a nonmotile, Gram-negative, encapsulated

coccobacillus A coccobacillus (plural coccobacilli), or bacilluscocco, is a type of bacterium with a shape intermediate between cocci (spherical bacteria) and bacilli (rod-shaped bacteria). Coccobacilli, then, are very short rods which may be mistaken for cocci ...

bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

found in the family

Pasteurellaceae The Pasteurellaceae comprise a large family of Gram-negative bacteria. Most members live as commensals on mucosal surfaces of birds and mammals, especially in the upper respiratory tract. Pasteurellaceae are typically rod-shaped, and are a notabl ...

. It exhibits β-hemolysis activity, thus explaining its growth on chocolate or

blood agar An agar plate is a Petri dish that contains a growth medium solidified with agar, used to Microbiological culture, culture microorganisms. Sometimes selective compounds are added to influence growth, such as antibiotics. Individual microorganism ...

, but must be supplemented with NAD ('V factor') to facilitate growth for one of its biological variants (biovar 1). As a facultative anaerobic pathogen, ''A. pleuropneumoniae'' may need CO₂ to grow. Depending on the biovar, the bacteria may or may not be positive for

urease Ureases (), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-containin ...

; both biovars are positive for

porphyrin Porphyrins ( ) are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). The parent of porphyrin is porphine, a rare chemical com ...

Porcine pleuropneumonia

''Actinobacillus pleuropneumoniae'' was found to be the causative agent for up to 20% of all bacterial

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...

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

pleuropneumonia can be attributed to its virulence factors. The symptoms include respiratory distress, bloodstained discharge (usually frothy) from the mouth, fever,

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

, mild

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

cyanosis Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...

, lethargy, and spontaneous

abortion Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregn ...

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. Not uncommonly,r mortality rates can reach 20-80% in fattening pigs, with similarly high morbidity. Pigs that do survive the disease remain as carriers and spread the bacterium to other swine. Several bacterial combinations are seen ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'', the most common simultaneous infection being ''

Pasteurella multocida ''Pasteurella multocida'' is a Gram-negative, nonmotile, penicillin-sensitive coccobacillus of the family Pasteurellaceae. Strains of the species are currently classified into five serogroups (A, B, D, E, F) based on capsular composition and ...

''. Treatment must be immediate and continuous. Antibiotics used include

ceftiofur Ceftiofur is an antibiotic of the cephalosporin type (third generation), licensed for use in veterinary medicine. It was first described in 1987. It is marketed by pharmaceutical company Zoetis as Excenel, Naxcel, and Excede and is also the active ...

tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including Acne vulgaris, acne, cholera, brucellosis, plague (disease), plague, malaria, and sy ...

, synthetic

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

tylosin Tylosin is a macrolide antibiotic and bacteriostatic feed additive used in veterinary medicine. It has a broad spectrum of activity against Gram-positive organisms and a limited range of Gram-negative organisms. It is found naturally as a ferme ...

, and

sulfonamides In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...

Serotypes

Nineteen different

serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epi ...

variants (serovars) have been recognized for ''A. pleuropneumoniae'', based on the different capsular

polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wa ...

s exhibited. Two different biovars exist, with biovar 1 having 13 different serovars and biovar 2 having two serovars. Differences in virulence potential,

immunogenicity Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injectio ...

, 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.

Pathophysiology

The bacterium rapidly colonizes the host and attaches to the

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

of the tonsils, moving down to the respiratory tract using type IV fimbriae. As the bacteria replicate, they release

cytotoxin Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating c ...

s (in the form of Apx toxins),

hemolysin Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acqu ...

s and the

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

s (LPSs)on their outer membranes. The subsequent

lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

causes a release of

lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...

s, which in turn cause the tissue damage seen in porcine pleuropneumonia. Members of the family Pasteurellaceae routinely change the cellular processes of the infected cell. In particular, ''A. pleuropneumoniae'' activates the creation of various

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

s such as

interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...

1β (IL-1β), IL-8, and tumor necrosis factor-alpha (

TNF-α Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

). IL-8 is itself a chemical signal used to attract

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

s to the infection site. The typical presentation of ''A. pleuropneumoniae'' in pigs is the characteristic demarcated

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

s in the middle, cranial, and caudal lobes of the

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

s. Areas of severe pneumonic growth are dark and consolidated. In the case of chronically infected pigs, pleural adhesions and

abscess An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...

es are normally found. Histological studies of infected lung tissue normally showcase lung

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

infiltration,

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

and

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

activation, and an

exudate An exudate is a fluid emitted by an organism through pores or a wound, a process known as exuding or exudation. ''Exudate'' is derived from ''exude'' 'to ooze' from Latin ''exsūdāre'' 'to (ooze out) sweat' (''ex-'' 'out' and ''sūdāre'' 'to ...

. Severe

hemolysis Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...

or hemorrhaging is also present. Several virulence factors account for the remarkable

pathogenicity In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

of ''A. pleuropneumoniae''. The more important ones include the production and release of the Apx toxins, the ability to produce a

biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...

, its LPS layer, capsule

s, and its ability to survive within an iron-limited environment. Of these, the most important are its capsule and Apx toxin production. The Apx toxin, a member of the

RTX toxin The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein se ...

family, is subdivided into four types: ApxI through ApxIV. As a pore-forming

exotoxin An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, simi ...

, Apx toxin lyses alveolar

epithelial cell Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

endothelial cell The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s, and

s. Each serotype expresses different levelss 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 Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...

and is expressed by serovars 2, 3, 4, 6, 8, and 15.

Epidemiology

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 does not survive for a significant 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.

Economic impact

''A. pleuropneumoniae'' has a profound economic impact on pork production and pig farmers. In 1995, Its infections cost the U.S. economy about $30 million. Such losses usually result from medication and veterinary expenses, increased mortality of pigs, extra labor, and other factors, such as reduced weight gain.

References

External links

Type strain of ''Actinobacillus pleuropneumoniae'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q343332 Bacteria described in 1983 Pasteurellales