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

2011 ◽  
Vol 18 (10) ◽  
pp. 1689-1694 ◽  
Author(s):  
Renuka Subramaniam ◽  
Sudarvili Shanthalingam ◽  
Jegarubee Bavananthasivam ◽  
Abirami Kugadas ◽  
Kathleen A. Potter ◽  
...  

ABSTRACTBighorn sheep (BHS) are more susceptible than domestic sheep (DS) toMannheimia haemolyticapneumonia. Although both species carryM. haemolyticaas a commensal bacterium in the nasopharynx, DS carry mostly leukotoxin (Lkt)-positive strains while BHS carry Lkt-negative strains. Consequently, antibodies to surface antigens and Lkt are present at much higher titers in DS than in BHS. The objective of this study was to determine whether repeated immunization of BHS with multivalentMannheimia-Bibersteiniavaccine will protect them uponM. haemolyticachallenge. Four BHS were vaccinated with a culture supernatant vaccine prepared fromM. haemolyticaserotypes A1 and A2 andBibersteinia trehalosiserotype T10 on days 0, 21, 35, 49, and 77. Four other BHS were used as nonvaccinated controls. On the day of challenge, 12 days after the last immunization, the mean serum titers of Lkt-neutralizing antibodies and antibodies to surface antigens againstM. haemolyticawere 1:160 and 1:4,000, respectively. Following intranasal challenge withM. haemolyticaA2 (1 × 105CFU), all four control BHS died within 48 h. Necropsy revealed acute fibrinonecrotic pneumonia characteristic ofM. haemolyticainfection. None of the vaccinated BHS died during the 8 weeks postchallenge observation period. Radiography at 3 weeks postchallenge revealed no lung lesions in two vaccinated BHS and mild lesions in the other two, which resolved by 8 weeks postchallenge. These results indicate that if BHS can be induced to develop high titers of Lkt-neutralizing antibodies and antibodies to surface antigens, they are likely to surviveM. haemolyticachallenge which is likely to reduce the BHS population decline due to pneumonia.

2011 ◽  
Vol 18 (7) ◽  
pp. 1133-1138 ◽  
Author(s):  
Caroline N. Herndon ◽  
Sudarvili Shanthalingam ◽  
Donald P. Knowles ◽  
Douglas R. Call ◽  
Subramaniam Srikumaran

ABSTRACTMannheimia haemolyticaconsistently causes fatal bronchopneumonia in bighorn sheep (BHS;Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related speciesOvis aries(domestic sheep [DS]). In BHS herds affected by pneumonia, lamb recruitment is severely impaired for years subsequent to an outbreak. We hypothesized that a lack of maternally derived antibodies (Abs) againstM. haemolyticaprovides an immunologic basis for enhanced susceptibility of BH lambs to population-limiting pneumonia. Therefore, the objective of this study was to determine the titers of Abs directed againstM. haemolyticain the sera of BH and domestic lambs at birth through 12 weeks of age. Results revealed that BH lambs had approximately 18-fold lower titers of Ab against surface antigens ofM. haemolyticaand approximately 20-fold lower titers of leukotoxin-neutralizing Abs than domestic lambs. The titers of leukotoxin-neutralizing Abs in the serum and colostrum samples of BH ewes were approximately 157- and 50-fold lower than those for domestic ewes, respectively. Comparatively, the higher titers of parainfluenza 3 virus-neutralizing Abs in the BH lambs ruled out the possibility that these BHS had an impaired ability to passively transfer Abs to their lambs. These results suggest that lower levels of leukotoxin-neutralizing Abs in the sera of BH ewes, and resultant low Ab titers in their lambs, may be a critical factor in the poor lamb recruitment in herds affected by pneumonia.


2014 ◽  
Vol 170 (3-4) ◽  
pp. 278-283 ◽  
Author(s):  
R. Subramaniam ◽  
S. Shanthalingam ◽  
J. Bavananthasivam ◽  
A. Kugadas ◽  
B. Raghavan ◽  
...  

2016 ◽  
Vol 4 (4) ◽  
Author(s):  
Abirami Kugadas ◽  
Jodi L. Humann ◽  
Sebastián Aguilar Pierlé ◽  
Subramaniam Srikumaran ◽  
Kelly A. Brayton

Here, we report the genome sequence for Bibersteinia trehalosi strain Y31, isolated from the lungs of a bighorn sheep ( Ovis canadensis ) that had succumbed to pneumonia, which exhibits proximity-dependent inhibition (PDI) of Mannheimia haemolytica . The sequence will be used to understand the mechanism of PDI for these organisms.


2012 ◽  
Vol 78 (18) ◽  
pp. 6683-6688 ◽  
Author(s):  
Jegarubee Bavananthasivam ◽  
Rohana P. Dassanayake ◽  
Abirami Kugadas ◽  
Sudarvili Shanthalingam ◽  
Douglas R. Call ◽  
...  

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.


2015 ◽  
Vol 83 (10) ◽  
pp. 3982-3988 ◽  
Author(s):  
Sai A. Batra ◽  
Sudarvili Shanthalingam ◽  
Gerhard R. Munske ◽  
Bindu Raghavan ◽  
Abirami Kugadas ◽  
...  

Mannheimia haemolyticacauses pneumonia in domestic and wild ruminants. Leukotoxin (Lkt) is the most important virulence factor of the bacterium. It is encoded within the four-genelktCABDoperon:lktA encodes the structural protoxin, andlktCencodes atrans-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 bylktBandlktD. 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 toM. haemolyticainfection. 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 anin vitrocytotoxicity 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 ofM. haemolyticaLkt but that it enhances the potency of the toxin.


1998 ◽  
Vol 37 (02) ◽  
pp. 130-133
Author(s):  
T. Kishimoto ◽  
Y. Iida ◽  
K. Yoshida ◽  
M. Miyakawa ◽  
H. Sugimori ◽  
...  

AbstractTo evaluate the risk factors for hypercholesterolemia, we examined 4,371 subjects (3,207 males and 1,164 females) who received medical checkups more than twice at an AMHTS in Tokyo during the period from 1976 through 1991; and whose serum total cholesterol was under 250 mg/dl. The mean follow-up duration was 6.6 years. A self-registering questionnaire was administered at the time of the health checkup. The endpoint of this study was the onset of hypercholesterolemia when the level of serum total cholesterol was 250 mg/dl and over. We compared two prognosis groups (normal and hypercholesterol) in terms of age, examination findings and lifestyle. After assessing each variable, we employed Cox's proportional hazards model analysis to determine the factors related to the occurrence of hypercholesterolemia. According to proportional hazards model analysis, total cholesterol, triglyceride and smoking at the beginning, and hypertension during the observation period were selected in males; and total cholesterol at the beginning and age were selected in females to determine the factors related to the occurrence of hypercholesterolemia.


1995 ◽  
Vol 74 (02) ◽  
pp. 622-625 ◽  
Author(s):  
H H Brackmann ◽  
R Egbring ◽  
A Ferster ◽  
P Fondu ◽  
J M Girardel ◽  
...  

SummaryThe pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma.Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.


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