Mycoplasma ovipneumoniae can predispose bighorn sheep to fatal Mannheimia haemolytica pneumonia

Dassanayake, Rohana P.; Shanthalingam, Sudarvili; Herndon, Christopher N.; Subramaniam, Renuka; Lawrence, Paulraj K.; Bavananthasivam, Jegarubee; Cassirer, E. Frances; Haldorson, Gary J.; Foreyt, William J.; Rurangirwa, Fred R.; Knowles, Donald P.; Besser, Thomas E.; Srikumaran, Subramaniam

doi:10.1016/j.vetmic.2010.04.011

Cited by 77 publications

(64 citation statements)

References 15 publications

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“…Experimental inoculation studies have shown that M. ovipneumoniae does not cause fatal pneumonia in BHS lambs (5). Nevertheless, it can predispose adult BHS to M. haemolytica pneumonia (6,14). It is not clear whether M. ovipneumoniae is a necessary predisposing agent for BHS pneumonia.…”

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confidence: 99%

Proximity-Dependent Inhibition of Growth of Mannheimia haemolytica by Pasteurella multocida

Bavananthasivam

Dassanayake

Kugadas

et al. 2012

Appl Environ Microbiol

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ABSTRACTMannheimia haemolytica,Pasteurella multocida, andBibersteinia trehalosihave been identified in the lungs of pneumonic bighorn sheep (BHS;Ovis canadensis). Of these pathogens,M. haemolyticahas been shown to consistently cause fatal pneumonia in BHS under experimental conditions. However,M. haemolyticahas been isolated by culture less frequently than the other bacteria. We hypothesized that the growth ofM. haemolyticais inhibited by other bacteria in the lungs of BHS. The objective of this study was to determine whetherP. multocidainhibits the growth ofM. haemolytica. Although in monoculture both bacteria exhibited similar growth characteristics, in coculture withP. multocidathere was a clear inhibition of growth ofM. haemolytica. The inhibition was detected at mid-log phase and continued through the stationary phase. When cultured in the same medium, the growth ofM. haemolyticawas inhibited when both bacteria were separated by a membrane that allowed contact (pore size, 8.0 μm) but not when they were separated by a membrane that limited contact (pore size, 0.4 μm). Lytic bacteriophages or bactericidal compounds could not be detected in the culture supernatant fluid from monocultures ofP. multocidaor fromP. multocida-M. haemolyticacocultures. These results indicate thatP. multocidainhibits the growth ofM. haemolyticaby a contact- or proximity-dependent mechanism. If the inhibition of growth ofM. haemolyticabyP. multocidaoccursin vivoas well, it could explain the inconsistent isolation ofM. haemolyticafrom the lungs of pneumonic BHS.

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confidence: 99%

Proximity-Dependent Inhibition of Growth of Mannheimia haemolytica by Pasteurella multocida

Bavananthasivam

Dassanayake

Kugadas

et al. 2012

Appl Environ Microbiol

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“…Serotype 2 is predominant in pneumonia in domestic sheep (37,38). However, BHS are susceptible to both serotypes 1 and 2 of M. haemolytica (6,25,(39)(40)(41). This study was conducted with serotype 1.…”

Section: Discussionmentioning

confidence: 99%

Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep

et al. 2015

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c Mannheimia haemolytica causes pneumonia in domestic and wild ruminants. Leukotoxin (Lkt) is the most important virulence factor of the bacterium. It is encoded within the four-gene lktCABD operon: lktA encodes the structural protoxin, and lktC encodes a trans-acylase that adds fatty acid chains to internal lysine residues in the protoxin, which is then secreted from the cell by a type 1 secretion system apparatus encoded by lktB and lktD. It has been reported that LktC-mediated acylation is necessary for the biological effects of the toxin. However, an LktC mutant that we developed previously was only partially attenuated in its virulence for cattle. The objective of this study was to elucidate the role of LktC-mediated acylation in Lkt-induced cytotoxicity. We performed this study in bighorn sheep (Ovis canadensis) (BHS), since they are highly susceptible to M. haemolytica infection. The LktC mutant caused fatal pneumonia in 40% of inoculated BHS. On necropsy, a large number of necrotic polymorphonuclear leukocytes (PMNs) were observed in the lungs. Lkt from the mutant was cytotoxic to BHS PMNs in an in vitro cytotoxicity assay. Flow cytometric analysis of mutant Lkt-treated PMNs revealed the induction of necrosis. Scanning electron microscopic analysis revealed the presence of pores and blebs on mutant-Lkt-treated PMNs. Mass spectrometric analysis confirmed that the mutant secreted an unacylated Lkt. Taken together, these results suggest that acylation is not necessary for the cytotoxic activity of M. haemolytica Lkt but that it enhances the potency of the toxin. Mannheimia haemolytica is a respiratory pathogen of domestic and wild ruminants (1-3). It is the most important bacterial pathogen of bovine respiratory disease complex, which costs the U.S. cattle industry alone more than $1 billion (4). M. haemolytica is also an important pathogen of pneumonia in bighorn sheep (Ovis canadensis) (BHS), which is the primary disease responsible for the drastic decline of BHS populations in North America from an estimated 2 million animals in the 1800s to less than 70,000 at the present time (5). Under the experimental conditions, M. haemolytica consistently caused 100% mortality in BHS within 2 to 3 days (6-8). The bacterium possesses several virulence factors, including the capsule, outer membrane proteins, lipopolysaccharide, and leukotoxin (Lkt). Based on the fact that Lkt deletion mutants do not cause mortality (6) or cause reduced mortality and milder lung lesions (9, 10), Lkt has been accepted as the primary virulence factor of M. haemolytica. The 104-kDa Lkt is absolutely specific for ruminant leukocytes (11). Previously, we have shown that the molecular basis for the ruminant specificity of Lkt rests in its binding to the signal peptide of CD18; the signal peptide remains intact in mature CD18 molecules on ruminant leukocytes, unlike that of nonruminants, which is cleaved (12). Although all ruminant leukocyte subsets are susceptible to Lkt-induced cytolysis, polymorphonuclear leukocytes (PMNs) are the most su...

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“…Culture results were further confirmed by genus-specific PCR as previously described (5). All M. haemolytica and B. trehalosi cultures were tested for the presence of the lktA gene by lktA gene-specific PCR (6).…”

Section: Methodsmentioning

confidence: 99%

A Multivalent Mannheimia-Bibersteinia Vaccine Protects Bighorn Sheep against Mannheimia haemolytica Challenge

Subramaniam

Shanthalingam

Bavananthasivam

et al. 2011

Clin. Vaccine Immunol.

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The bighorn sheep (BHS; Ovis canadensis) population in North America has declined drastically during the last century due to a combination of factors, including loss of habitat, competition for forage with domestic livestock, predation, and disease. Pneumonia is the primary disease that causes significant mortality in BHS (2, 26). Although Mannheimia haemolytica, Bibersteinia trehalosi, and Pasteurella multocida have been isolated from several pneumonia outbreaks, only M. haemolytica has been shown to consistently cause fatal pneumonia in BHS under experimental conditions (4, 7, 9, 22). Virulence factors of M. haemolytica include capsule, outer membrane proteins, neuraminidase, lipopolysaccharide, and a potent exotoxin called leukotoxin (Lkt), which is cytolytic to all subsets of ruminant leukocytes (3,14). Based on the fact that Lkt deletion mutants cause no mortality in BHS (4) and lower mortality and mild lung lesions in cattle (12,19,24), Lkt has been accepted as the major virulence factor of this organism. Although M. haemolytica causes pneumonia in all ruminants, BHS are highly susceptible to this disease (4,7,9,22). There are a number of potential factors contributing to the apparent difference in susceptibility to pneumonia. Enhanced susceptibility of polymorphonuclear leukocytes (PMNs) from BHS to Lkt-induced cytolysis is one of the factors responsible for the higher susceptibility of BHS (20,22), which underscores the importance of Lkt-neutralizing antibodies (Lkt-nAb) for protection of BHS against M. haemolytica pneumonia.Vaccination studies in cattle have shown that antibodies against Lkt and surface antigens of M. haemolytica confer protection against experimental challenge (13,21) and that such antibodies can be induced by vaccination of cattle or BHS with log-phase culture supernatant fluid (1,13,16,27). However, to date systematic analysis of the response of BHS to vaccination and subsequent challenge with M. haemolytica has not been performed. Thus, unambiguous data on the role of antibodies in protection of BHS against pneumonia caused by M. haemolytica are not available. Several pneumonia outbreaks have occurred in the recent past, resulting in the death of large numbers of BHS (17). Thus, there is a critical need for development of efficacious vaccines to protect BHS against pneumonia. This study represents an initial step in addressing this need.

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Mycoplasma ovipneumoniae can predispose bighorn sheep to fatal Mannheimia haemolytica pneumonia

Cited by 77 publications

References 15 publications

Proximity-Dependent Inhibition of Growth of Mannheimia haemolytica by Pasteurella multocida

Proximity-Dependent Inhibition of Growth of Mannheimia haemolytica by Pasteurella multocida

Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep

A Multivalent Mannheimia-Bibersteinia Vaccine Protects Bighorn Sheep against Mannheimia haemolytica Challenge

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