Pasteurella multocida is a Gram-negative, nonmotile, penicillin-sensitive coccobacillus from the family Pasteurellaceae. P. multocida is the cause of a range of diseases in mammals and birds, including fowl cholera in poultry, atrophic rhinitis in pigs, and bovine hemorrhagic septicemia in cattle and buffalo. It can also cause a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets. Many mammals (including domestic cats and dogs) and birds harbor it as part of their normal respiratory microbiota, rendering them silent sources of infection.
History Pasteurella multocida was first found in 1878 in cholera-infected birds. However, it was not isolated until 1880, by Louis Pasteur, in whose honor Pasteurella is named.
Taxonomy
Subspecies P. multocida is traditionally divided into three subspecies by biochemical phenotype: P. multocida subsp. multocida is defined as dulcitol(-), sorbitol(+). P. multocida subsp. septica is defined as dulcitol(-), sorbitol(+). P. multocida subsp. gallicida is defined as dulticol(+).
A variant classification replaces the ambiguous Andrades sorbitol growth test with a test for α-glucosidase (α-Glu) activity. It agrees well with single-primer (M13 core) PCR fingerprinting but not so well with the original sorbitol test.
This biochemical classification is generally used for epidemology. The different ability to digest these sugar alcohols may have a meaning in ecology and pathogenesis.
Serology Strains of the species are serologically categorized by a combination of two designations: one of five Carter serogroups (A, B, D, E, F) based on the capsule and one of 16 Heddleston serovars (1–16) based on lipopolysaccharide (LPS). To classify a strain serologically, the capsule and the LPS are separately tested using pre-made antibodies. The two results are then written in a combined serotype (e.g. A:2, C:1), for a total of 80 possibilities. (It is also possible for the capsule to not be present, written as "-".)
The chemical structure for A, D, and F capsules are known to be hyaluronic acid, heparin, and chondroitin respectively; group B is known to contain some copolymer of arabinose, mannose, and galactose. The chemical structure for LPS of all 16 serovars are known, as are many types not included in the Heddleston system.
Another indication system is Namioka-Carter, commonly encountered in bovine literature. The capsule classification is the same as Carter's but there are instead 11 somatic "O groups" again supposedly corresponding to the LPS. Results are written with the serovar first, e.g. 6:B and 6:E. Namioka's method for LPS resolution (tube agglutination) is not as powerful as Heddleston's gel diffusion precipitation test but may be easier to perform. There is not a good correspondence between any pair of Namioka and Heddleston numbers, suggesting at least some of the antisera in one of the systems is not as purely descriptive of LPS as originally thought.
Molecular typing The genetic locus responsible for the capsular serological variation is known, so "molecular serotyping" (i.e. deducing the serotype by the genotype) has become routine and in the overwhelming majority of cases gives identical results, generally only producing mismatches on novel combinations of mutations. The locus for the LPS is also known, but only six LPS genotypes are defined due to some LPS serovars being produced from very minor genetic change that are hard to differentiate by PCR fingerprinting. They are designated L1 (1, 14), L2 (2, 5), L3 (3, 4), L4 (6), L5 (9), L6 (10, 11, 12, 15), L7 (8, 13), L8 (16), with the parenthezied numbers being the corresponding serovars. Again, the two designations are usually combined: for example, two strains with serotypes A:1 and A:14 should both test as having the genotype A:L1.
Two multilocus sequence typing schemes have been defined, an RIDIC scheme based on fragments of 7 housekeeping genes (adk, est, gdh, mdh, pgi, pmi, g6pd "zwf") originally defined for avian isolates and a multihost scheme based on different fragments of 7 housekeeping genes (adk, aroA, deoD, gdhA, g6pd, mdh, pgi). The former scheme has 365 genotypes (ST1–265, ST for "sequence type") and the latter has 109 (ST1–109); to differentate between those two one usually prefix a designation like "RIRDC ST365", etc. Because the two schemes use overlapping areas, a ST from one scheme usually only corresponds to a handful in another, though no strict conversion table can be made.
MLST can be used in addition to the capsule:LPS genotype as these systems are orthogonal. Because MLST uses housekeeping genes unrelated to virluence, it is not subject to as much selection pressure and tends to more closely show the history of the strains as measured by more intensive whole-genome comparisons.
Disease Pasteurella multocida causes a range of diseases in wild and domesticated animals, as well as humans. The bacterium is found in birds, cats, dogs, rabbits, cattle, and pigs. In birds, P. multocida causes avian or fowl cholera disease; a significant disease present in commercial and domestic poultry flocks worldwide, particularly layer flocks and parent breeder flocks.
In most species the majority of infections are caused by a handful of serotypes, partly explained by the fact that the two molecules used for serotype classification are also the host's immune system's "first impression" of this bacterium. However, capsule and LPS are only two of the bacterium's virulence factors with a role in host selection, and two strains of the same cap:LPS genotype may actually turn out quite different when examined using MLST or whole-genome comparison.
Avians P. multocida strains that cause fowl cholera in poultry typically belong to the serovars 1, 3, and 4. In the wild, fowl cholera has been shown to follow bird migration routes, especially of snow geese. The P. multocida serotype-1 is most associated with avian cholera in North America, but the bacterium does not linger in wetlands for extended periods of time.Blanchlong, JA. "Persistence of pasteurella multocida in wetlands following avian cholera outbreaks." Journal of Wildlife diseases, 2006; 42(1):33-39
Mammals P. multocida causes atrophic rhinitis in pigs;Eliás B, Hámori D. Data on the aetiology of swine atrophic rhinitis. V. The role of genetic factors. Acta Vet Acad Sci Hung. 1976;26(1):13–19. [PubMed] it also can cause pneumonia or bovine respiratory disease in cattle.Irsik, M B Bovine respiratory disease associated with Mannheimia Haemolytica or pastuerella multocida. VM 163, University of Florida It may be responsible for mass mortality in saiga antelopes.Richard A. Kock, Mukhit Orynbayev, Sarah Robinson, Steffen Zuther, Navinder J. Singh, Wendy Beauvais, Eric R. Morgan, Aslan Kerimbayev, Sergei Khomenko, Henny M. Martineau, Rashida Rystaeva, Zamira Omarova, Sara Wolfs, Florent Hawotte, Julien Radoux and Eleanor J. Milner-Gulland: Saigas on the brink: Multidisciplinary analysis of the factors influencing mass mortality events. Science Advances 17 Jan 2018: Vol. 4, no. 1, eaao2314 DOI: 10.1126/sciadv.aao2314
Humans In humans, P. multocida is the most common cause of wound infections after dog or cat bites. The infection usually shows as soft tissue inflammation within 24 hours. High leukocyte and neutrophil counts are typically observed, leading to an inflammatory reaction at the infection site (generally a diffuse, localized cellulitis). It can also infect other locales, such as the respiratory tract, and is known to cause regional lymphadenopathy (swelling of the lymph nodes). In more serious cases, a bacteremia can result, causing an osteomyelitis or endocarditis. Patients with a joint replacement (perhaps notably knee replacement) in place may, in particular, be at risk of secondary infection of that joint during an episode of P multocida cellulitis/bacteraemia. The bacteria may also cross the blood–brain barrier and cause meningitis.Casolari C, Fabio U. Isolation of Pasteurella multocida from Human Clinical Specimens: First Report in Italy. European Journal of Epidemiology. Sept 1988; 4(3):389-90
Virulence Pasteurella. multocida expresses a range of virulence factors including a polysaccharide capsule and the variable carbohydrate surface molecule, lipopolysaccharide (LPS). The capsule has been shown in strains of serogroups A and B to help resist phagocytosis by host immune cells and capsule type A has also been shown to help resist complement-mediated lysis.Chung JY, Wilkie I, Boyce JD, Townsend KM, Frost AJ, Ghoddusi M, Adler B: Role of capsule in the pathogenesis of fowl cholera caused by Pasteurella multocida serogroup A. Infect Immun 2001, 69(4):2487-2492.Boyce JD, Adler B: The capsule is a virulence determinant in the pathogenesis of Pasteurella multocida M1404 (B:2). Infect Immun 2000, 68(6):3463-3468. The LPS produced by P. multocida consists of a hydrophobic lipid A molecule (that anchors the LPS to the outer membrane), an inner core, and an outer core, both consisting of a series of sugars linked in a specific way. There is no O-antigen on the LPS and the molecule is similar to LPS produced by Haemophilus influenzae and the lipooligosaccharide of Neisseria meningitidis. A study in a serovar 1 strain showed that a full-length LPS molecule was essential for the bacteria to be fully virulent in chickens.Harper M, Cox AD, St Michael F, Wilkie IW, Boyce JD, Adler B. A heptosyltransferase mutant of Pasteurella multocida produces a truncated lipopolysaccharide structure and is attenuated in virulence. Infect. Immun. 2004; 72(6):3436-43.
Strains that cause atrophic rhinitis in pigs are unique as they also have P. multocida toxin (PMT) residing on a bacteriophage. PMT is responsible for the twisted snouts observed in pigs infected with the bacteria. This toxin activates Rho GTPases, which bind and hydrolyze GTP, and are important in actin stress fiber formation. Formation of stress fibers may aid in the endocytosis of P. multocida. The host cell cycle is also modulated by the toxin, which can act as an intracellular mitogen.Lacerda HM, Lax AJ, Rozenqurt E. Pasteurella multocida toxin, a potent intracellularly acting mitogen, induces p125FAK and paxillin tyrosine phosphorylation, actin stress fiber formation, and focal contact assembly in Swiss 3T3 cells. J Biol Chem. 5 Jan 1996; 271(1):439-45.
P. multocida has been observed invading and replicating inside host amoebae, causing lysis in the host.
Growth characteristics P. multocida will grow at on blood or chocolate agar, HS agar,, by Younginfrontier, . HS agar, by Laboratorios CONDA, PDF. but will not grow on MacConkey agar. Colony growth is accompanied by a characteristic "mousy" odor due to metabolic products.
A facultative anaerobe, P. multocida it is oxidase-positive and catalase-positive. It can also ferment a large number of carbohydrates in anaerobic conditions. The survival of P. multocida bacteria has also been shown to be increased by the addition of salt into their environments. Levels of sucrose and pH also have been shown to have minor effects on bacterial survival.Bredy, JP. "The effects of six environmental variables on Pasteurella multocida populations in water." Journal of Wildlife Diseases, vol. 25, no. 2 (232–239)
Diagnosis and treatment Diagnosis of the bacterium in humans was traditionally based on clinical findings, and culture and serological testing, but false negatives have been a problem due to easy death of P. multocida, and serology cannot differentiate between current infection and previous exposure. The quickest and most accurate method for confirming an active P. multocida infection is molecular detection using polymerase chain reaction.Miflin, J.K. and Balckall, P.J. (2001) Development of a 23 SrRNA-based PCR assay for the identification of Pasteurella multocida. Lett. Appl. Microbiol. 33: 216–221