A three-way comparative genomic analysis of Mannheimia haemolytica isolates

<p>Abstract</p> <p>Background</p> <p><it>Mannhemia haemolytica </it>is a Gram-negative bacterium and the principal etiological agent associated with bovine respiratory disease complex. They transform from a benign commensal to a deadly pathogen, during stress such as viral infection and transportation to feedlots and cause acute pleuropneumonia commonly known as shipping fever. The U.S beef industry alone loses more than one billion dollars annually due to shipping fever. Despite its enormous economic importance there are no specific and accurate genetic markers, which will aid in understanding the pathogenesis and epidemiology of <it>M. haemolytica </it>at molecular level and assist in devising an effective control strategy.</p> <p>Description</p> <p>During our comparative genomic sequence analysis of three <it>Mannheimia haemolytica </it>isolates, we identified a number of genes that are unique to each strain. These genes are "high value targets" for future studies that attempt to correlate the variable gene pool with phenotype. We also identified a number of high confidence single nucleotide polymorphisms (hcSNPs) spread throughout the genome and focused on non-synonymous SNPs in known virulence genes. These SNPs will be used to design new hcSNP arrays to study variation across strains, and will potentially aid in understanding gene regulation and the mode of action of various virulence factors.</p> <p>Conclusions</p> <p>During our analysis we identified previously unknown possible type III secretion effector proteins, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated sequences (Cas). The presence of CRISPR regions is indicative of likely co-evolution with an associated phage. If proven functional, the presence of a type III secretion system in <it>M. haemolytica </it>will help us re-evaluate our approach to study host-pathogen interactions. We also identified various adhesins containing immuno-dominant domains, which may interfere with host-innate immunity and which could potentially serve as effective vaccine candidates.</p

Clinical effects of Carprofen during experimental bovine pneumonic mannheimiosis

peer reviewedM. haemolytica sérotype A1 (anciennement dénommée Pasteurella) est l’agent pathogène le plus fréquemment isolé lors de cas mortels de bronchopneumonie infectieuse bovine. M. haemolytica et ses deux principales toxines, le lipopolysaccharide (LPS) et la leucotoxine (LktA), induisent le recrutement, l’activation et la nécrose des neutrophiles fortement impliqués dans la pathogénie des broncho-pneumonies bovines à Mannheimia (BPM). Le but de notre étude fut de déterminer l’effet d’une administration thérapeutique de carprofène (Rimadyl® bovins*), un anti-inflammatoire non steroïdien (AINS), sur l’évolution des paramètres cliniques et nécropsiques dans un modèle de BPM aiguë expérimentalement induite chez des veaux. Les veaux ont été inoculés par M. haemolytica et ses toxines à T0, et traités (n=6) ou non (n=6) au caprofène (1,4 mg/kg IV) à T+1. Les paramètres cliniques et biochimiques ont été évalués une (T+1), trois (T+3) et sept (T+7) heures après inoculation. A T+1, l’établissement de la pathologie a été confirmée de manière significative par l’aggravation du score clinique et l’augmentation de la fréquence respiratoire chez l’ensemble des veaux. L’administration de carprofène a empêché une diminution de la saturation du sang en oxygène à T+3, une dégradation du score clinique et une augmentation de la lactatémie à T+7. Pour ces trois paramètres, les différences observées étaient significatives. Al’autopsie, l’étendue des lésions pulmonaires était diminuée de manière significative dans le groupe traité au carprofène. Ces résultats montrent que l’injection de carprofène après l’apparition des premiers signes cliniques de BPM permet d’améliorer l’état clinique des veaux et de réduire l’étendue des lésions pulmonaires.M. haemolytica serotype A1 (formerly known as Pasteurella) is the most important and commonly isolated bacterial pathogen from fatal cases of bovine fibrinous pleuroneumonia. M. haemolytica and its two principal toxins, the lipopolysaccharides (LPS) and the leukotoxin (LktA) induce the recruitment, the activation and the necrosis of neutrophils involved in the pathogenicity of bovine pneumonic mannheimiosis (BPM). The objective of this study was to determine whether systemic therapy with carprofène (Rimadyl®*), a non-steroidal anti-inflammatory drug, improves the disease development in an acute experimental model of BPM. The experimental pathology was induced by trans-tracheal inoculation of M. haemolytica and toxins at T0. One hour post-inoculation, six calves were treated intravenously with carprofen (1,4 mg/kg) while six placebo-treated calves received dose-matched volumes of sterile saline. The clinical and biochemical parameters were measured at one (T+1), three (T+3) and seven (T+7) hours after inoculation. Disease scores for carprofen treated calves were significantly lower than those for placebo-treated controls six hours (T+7) after treatment. These results were associated to a significantly oxygen saturation decrease at T+3 and a significantly blood lactate increase at T+7 in the control calves. Moreover, pulmonary lesions were significantly less extensive than those in the control group. Taken together, this finding suggest that pharmacological modulation by carprofen of pulmonary inflammation after appearance of acute BPM clinical signs leads to calves’ health enhancement and reduces the extent of gross pneumonic lesion