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The efficacy of an early and low inoculum-adjusted marbofloxacin treatment was evaluated on microbiological and clinical outcomes in calves infected with 4.107 CFU of Mannheimia haemolytica A1. Twenty-two calves were included based on their rectal temperature rise in the 10 h after challenge and allocated in four groups, receiving a single intramuscular injection of saline (CON), 2 mg/kg marbofloxacin 2–4 h after inclusion (early treatment, E2), 2 or 10 mg/kg marbofloxacin 35–39 h after inclusion (late treatments, L2, L10). In CON calves, M. haemolytica DNA loads in bronchoalveolar lavages continuously increased from inclusion to day 4, and were associated with persistent respiratory clinical signs and lung lesions. At times of early and late treatments, M. haemolytica loads ranged within 3.5–4 and 5.5–6 log10 DNA copies/mL, respectively. Early 2 mg/kg marbofloxacin treatment led to rapid and total elimination of bacteria in all calves. The late treatments induced a reduction of bacterial loads, but 3 of 6 L2 and 1 of 6 L10 calves were still positive for M. haemolytica at day 4. Except for CON calves, all animals exhibited clinical improvement within 24 h after treatment. However, early 2 mg/kg treatment was more efficacious to prevent pulmonary lesions, as indicated by the reduction of the extension and severity of gross lesions and by the histopathological scores. These results demonstrated for the first time that a reduced antibiotic regimen given at an early stage of the disease and targeting a low bacterial load could be efficacious in a natural bovine model of pneumonia.

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The incidence of clinical respiratory disease in 698 young beef bulls kept in 68 pens, and their exposure to respiratory pathogens after their arrival at 51 fattening operations in western France were assessed. Antibodies against bovine respiratory syncytial virus (BRSV), bovine herpesvirus type 1 (BHV-1), Mannheimia haemolytica and Mycoplasma bovis were measured by ELISA. The incidence risk of respiratory disease was 18.5 per cent during the first six weeks. Cases occurred in 37 of the 68 pens, and in these pens 30.9 per cent of the bulls were affected. Their exposure to BHV-1 was very limited. When they arrived a high proportion of the bulls were seropositive to M haemolytica and a high proportion seroconverted to BRSV, M haemolytica and M bovis within the first six weeks. The risk of incidence of respiratory disease was lower in the pens in which the bulls had been vaccinated against M haemolytica. Higher proportions of the bulls were affected in pens in which small proportions of the bulls were seropositive to M haemolytica or BRSV on arrival, and in pens in which high proportions of the bulls were exposed to M haemolytica or BRSV during the first six weeks.

Monitoring body temperature of newly received cattle allows for identification of fever episodes not visually detected by feedlot personnel (FENO). Information concerning the occurrence, duration, and impact on performance of these FENO is not available in the literature. Such information is crucial to assess the potential benefit of the identification and treatment of FENO. Therefore, the objectives of this study were to describe the occurrence and duration of FENO and to evaluate their impact on ADG. One hundred twelve beef bulls (initial BW = 346 ± 36 kg) were studied for 40 d after arrival at 3 French fattening operations. At d 1, each animal was administered orally a reticulo-rumen bolus, which allowed continuous measurement and recording of reticulo-rumen temperature. Animals were weighed on d 1 and 40. Bulls were observed twice daily by personnel for visual signs of apparent disease. Bulls that appeared ill, had a rectal temperature ≥39.7°C, and demonstrated symptoms consistent with bovine respiratory disease (BRD) were treated with antibiotics. After d 40, data obtained from the boluses were retrospectively analyzed using a cumulative sum test to detect significant increases in reticulo-rumen temperature considered as fever episodes. Numerous fever episodes (n = 449) were retrospectively detected in 110 bulls. Of these 449 fever episodes, 74% were not associated with any visually detected clinical signs of disease and thus were identified as FENO. These FENO were often transitory (75% lasted less than 47 h). However, 25% lasted from 47 to 263 h. Of the 112 bulls, 88 were treated for BRD with 20 and 7 animals treated, respectively, 2 and 3 times. In treated animals, fever episodes began 4 to 177 h (mean = 50 h) before BRD treatment. The duration of FENO was associated (P = 0.002) with a lesser ADG (d 1 to 40): -33 g/d for daily FENO duration. Our results demonstrated that FENO occurred frequently in bulls during the first weeks after entrance into a fattening operation and can last up to 11 d. The impact of FENO observed on ADG in this study indicated a potential benefit of treating affected animals, specifically those with FENO of long duration. However, further research is needed to determine the medical and economic relevance of such treatment.

Microbial access to host nutrients is a key factor of the host-pathogen interplay. With their nearly minimal genome, wall-less bacteria of the class Mollicutes have limited metabolic capacities and largely depend on host nutrients for their survival. Despite these limitations, host-restricted mycoplasmas are widely distributed in nature and many species are pathogenic for humans and animals. Yet, only partial information is available regarding the mechanisms evolved by these minimal pathogens to meet their nutrients and the contribution of these mechanisms to virulence. By using the ruminant pathogen Mycoplasma bovis as a model system, extracellular DNA (eDNA) was identified as a limiting nutrient for mycoplasma proliferation under cell culture conditions. Remarkably, the growth-promoting effect induced by supplementation with eDNA was associated with important cytotoxicity for actively dividing host cells, but not confluent monolayers. To identify biological functions mediating M. bovis cytotoxicity, we produced a library of transposon knockout mutants and identified three critical genomic regions whose disruption was associated with a non-cytopathic phenotype. The coding sequences (CDS) disrupted in these regions pointed towards pyruvate metabolism as contributing to M. bovis cytotoxicity. Hydrogen peroxide was found responsible for eDNA-mediated M. bovis cytotoxicity, and non-cytopathic mutants were unable to produce this toxic metabolic compound. In our experimental conditions, no contact between M. bovis and host cells was required for cytotoxicity. Further analyses revealed important intra-species differences in eDNA-mediated cytotoxicity and H2O2 production, with some strains displaying a cytopathic phenotype despite no H2O2 production. Interestingly, the genome of strains PG45 and HB0801 were characterized by the occurrence of insertion sequences (IS) at close proximity to several CDSs found disrupted in non-cytopathic mutants. Since PG45 and HB0801 produced no or limited amount of H2O2, IS-elements might influence H2O2 production in M. bovis. These results confirm the multifaceted role of eDNA in microbial communities and further identify this ubiquitous material as a nutritional trigger of M. bovis cytotoxicity. M. bovis may thus take advantage of the multiple sources of eDNA in vivo to modulate its interaction with host cells, a way for this minimal pathogen to overcome its limited coding capacity.

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