Untersuchungen zur Wirksamkeit einer Mannheimia-haemolytica-Adsorbatvakzine in Beziehung zur Immunitätslage von Mastkälbern aus dem Institut für Bakteriologie und Mykologie der Veterinärmedizinischen Fakultät der Universität Leipzig (140 S., 15 Abb., 18 Tab., 407 Lit.) Die Enzootische Bronchopneumonie des Rindes stellt einen der zentralen und wirtschaftlich bedeutsamsten Krankheitskomplexe in der Rinderaufzucht und –mast dar. Unter den Bedingungen der konzentrierten Stallhaltung größerer Tierpopulationen verursachen respiratorische Erkrankungen jährlich weltweit ökonomische Verluste in Höhe von mehreren Mrd. Dollar. In der vorliegenden Arbeit wurde unter Feldbedingungen in zwei Kälbermastbeständen die Wirksamkeit der Mannheimia-haemolytica-Adsorbatvakzine PRESPONSE? getestet. Anhand der erhobenen klinischen, bakteriologischen und serologischen Befunde konnten zudem Betrachtungen hinsichtlich des Zusammenhanges zwischen Transportbelastung und Gesundheits- bzw. Immunstatus der Tiere gemacht werden. In die Untersuchungen waren 123 Kälber aus einem Betrieb mit Zukauf und 162 Kälber sowie 57 hochtragende Kühe aus einem Bestand mit eigener Reproduktion involviert. Die Ergebnisse der 790 bakteriologischen Nasentupferuntersuchungen erbrachten keinen Nachweis von impfstoffinduzierten Modifikationen in der Zusammensetzung der Nasenschleimhautflora der Kälber. Andererseits verdeutlichten die Untersuchungsbefunde, daß insbesondere der Nachweis von Mannheimia-haemolytica-A1-Stämmen und toxischen Pasteurella-multocida-Stämmen eng mit dem respiratorischen Erkrankungsgeschehen im jeweiligen Bestand korrelierten. Die Dominanz dieser beiden Vertreter auf den Nasenschleimhäuten erkrankter Kälber unterstreichen deren ätiologische Bedeutung. Die ermittelten bestandsabhängigen Unterschiede im klinischen Ausprägungsgrad der respiratorischen Symptomatik akzentuierten ein weiteres Mal, daß Crowding und Transportstreß wesentliche nichtinfektiöse Faktoren im Pathogeneseprofil der EBP des Rindes repräsentieren. Das Spektrum der blutserologischen Untersuchungen umfaßte die Parameter Mannheimia-haemolytica-Antikörpertiter, Antikörperstatus pneumotrope Viren, IgG-Anti-Lipid-A sowie C-reaktives Protein. Im Verlauf der blutserologischen Untersuchungen konnten bei den Jungtieren keine signifikanten vakzineassoziierte Effekte nachgewiesen werden. Für die Betrachtungen zum Immunstatus der Kälber wurden vorrangig die Daten der IgG-Anti-Lipid-A- sowie der CRP-Bestimmungen herangezogen. Unter Berücksichtigung der altersspezifischen Konstellationen des juvenilen Immunsystems konnte anhand der erzielten Untersuchungsergebnisse nachgewiesen werden, daß diese beiden Parameter für die Einschätzung der Immunkompetenz von Kälbern geeignet sind. Insbesondere auf der Grundlage korrelativer Betrachtungen spiegelten sie deutlich die differenzierte Befähigung der Jungtiere zur Auseinandersetzung mit gramnegativen Infektionserregern wider. / Studies of the efficacy of adsorbed Mannheimia haemolytica vaccine in relation to the state of immunity of fat stock from the Insitute of Bacteriology and Mycology, Faculty of Veterinary Medicine, Leipzig University, Germany (140 pages, 15 figures, 18 tables, 407 references) Enzootic bronchopneumonia in cattle represents one of the crucial and economically important disease of breeding-calves and fat stock. Under the circumstances of concentrated mass production of cattle respiratory disease annually cause worldwide economic losses of several billions of dollars. In the thesis presented here the effectiveness of Mannheimia haemolytica adsorbed vaccine “Presponse TM” was tested under field conditions in two fat stock farms fattening calves. From the gained clinical, bacteriological and serological findings conclusions could be drawn concerning the connections between stress factors connected with transportation and health-/immune-state of the animals. 123 calves from a farm purchasing their new calves and 162 calves plus 57 highly pregnant cows from a farm with own reproduction were included in this study. The results of 790 bacteriologically examined nose swabs gave no hints to vaccine – induced modifications in the composition of the calves nasal mucosal flora. On the other hand the results make clear that specially the presence of Mannheimia haemolytica A1 strains and toxic Pasteurella multocida strains strongly correlates with respiratory disease cases in the concerned farms. The dominance of these two bacteria in the nasal mucosa of calves fallen ill emphasizes their aetiological importance. The results achieved showing the differences in the grades of clinical symptoms make evident that crowding and stress factors connected with transportation represent important non infectious factors in the pathogenetic profile of enzootic bronchopneumonia in cattle. The range of the accomplished bloodserological examinations included the following parameters: titer of antibodies against Mannheimia haemolytica, antibodies against pneumotropic viruses, IgG-anti-lipid-A as well as C-reactive protein. In the course of the bloodserological examinations no significant effects associated with vaccination were found in young cattle. For the consideration of the state of immunity of the calves mainly the data of the IgG anti lipid A and the CRP determinations were used. Under consideration of the age-specific constellation of the juvenile immune system from the achieved data it could be concluded that these two parameters are suitable for the appreciation of the immune competence of calves. Specially on the base of correlative considerations they reflect the differenciated ability of young cattle to deal with gram negative infectious agents.

Bovine Respiratory Disease Complex is a multifactorial disease affecting cattle worldwide resulting in high mortality and morbidity rates in the cattle farming industry. This complex is caused by multiple viral and bacterial pathogens such as Bovine Herpesvirus-1, Bovine Respiratory Syncytial Virus, Mannheimia haemolytica, and Pasteurella multocida; two of the main contributors to the initiation of this disease are Bovine Herpesvirus-1 and the bacteria, Mannheimia haemolytica. Together, these microbes co-infect immunocompromised cattle during times of increased stress and induce a severe pneumonic response along with other health complications. Research has been primarily focused on these microorganisms individually or their effect on the host, however there is a need to study them together due to the increased mortality rate associated with co-infections. In this study, we used Bovine Herpesvirus-1, Mannheimia haemolytica, Pasteurella multocida, and Bovine Respiratory Syncytial Virus to co-infect bovine tissue cultures to determine how they affect each other.

The objectives of this study were to evaluate the effect of number of stocker cattle in receiving pens (large: n=150 cattle; small: n=50 cattle) on 1) BRD morbidity/mortality, and performance, 2) antimicrobial use and prevalence of antimicrobial resistance in Mannheimia haemolytica, and 3) profitability of stocker operations. No differences were found for morbidity (p=0.5041). Mortality tended (p=0.0744) to be higher in large groups. BW increased (p LESS THAN 0.0001) over time. A treatment*day interaction (p=0.00592) was found for ADG, with largest gains for both groups from day 14-28. M. haemolytica recovery decreased (p=0.0002) over time. Antimicrobial resistance (p=0.0179) and MDR (p=0.0405) were higher in the small group. Treatment costs were higher in the small group ($1,093.53/hd) compared to large ($1,037.04/hd). Because of the nature of a pilot study, further research are needed to determine the effectiveness of reducing animals in a pen on health, growth, AMR, and profitability associated with stocker cattle.

The scope and application of high throughput techniques has expanded from studying a single genome, transcriptome or proteome to understanding complex environments at a greater resolution with the help of novel computational frameworks. Comprehensive structural annotation i.e. description of all functional elements in the genome, is required for measuring genome response accurately, using high throughput methods. Annotation of genome sequences using high throughput data from RNA-seq and proteomics experiments complement computational methods for identifying functional elements and can help validate existing in silico annotation, correct annotation errors, and could potentially identify novel functional elements. Re-annotation studies in recent times have revealed shortcomings of automated methods and the necessity to validate existing annotations using experimental data. This dissertation elucidates re-annotation of Mannheimia haemolytica, Pasteurella multocida and Histophilus somni, bacterial pathogens associated with bovine respiratory disease in cattle. Experimental re-annotation of these bacterial genomes using RNA-seq and proteomics enabled the validation of existing annotation and discovery of novel functional elements that can be utilized in future functional genomics studies. We also addressed the need for developing an automated bioinformatics workflow that is broadly applicable for bacterial genome re-annotation, by developing open source Perl pipeline that can use RNA-seq and proteomics data as input. Simultaneous analysis of host and pathogen gene expression profiling using metatranscriptomics approaches is necessary to improve our understanding of infectious diseases. Traditional methods for analysis of RNA-seq data do not address the impact of cross-mapping of reads to multiple genomes for data originating from a metatranscriptomic study. Analysis of sequence conservation between species can help determine a metric for cross mapping to correct for signal vs. noise. We generated artificial RNA-seq data and evaluated the impact of read length and sequence conservation on cross-mapping. Comparative genomics was used to identify a core and pan-genome for quantifying gene expression. Our results show that cross mapping between genomes can directly be related to evolutionary distance between these genomes and that an increase in RNA-seq read length tends to negate cross mapping.