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Introduction: «PathoCalf» represents a project promoted by the Swiss Federal Food Safety and Veterinary Office. It was the aim of this project to use laboratory diagnostic services for farms raising calves (dairy farms, fattening units, beef cow operations) and dealing with a herd health issue in order to obtain an overview about the spectrum of infectious agents and bacterial resistance patterns in Switzerland. From January 2015 to March 2018, the Bovine Health Service and the farm veterinarian straightened out 148 stock problems on 125 farms. For this, samples were collected from 342 animals. In addition, 98 necropsies were performed. The service related to «PathoCalf» was utilized most frequently related to stock problems with respiratory disease (40,5%; 60/148), gastrointestinal disease (37,2%, 55/148) and fatalities with unknown causation (8,8%, 13/148). The majority of all investigated animals (71,8%) were younger than 10 weeks of age. In calves suffering from respiratory disease, most frequently Pasteurella (P.) multocida was found (40,6%, 67/165), followed by mycoplasmen (35,8%, 59/165) and Mannheimia (M.) haemolytica (13,3%, 22/165). The proportion of tested P. multocida and M. haemolytica strains being resistant against oxytetracyline was 67,7% (42/62), 21,1% (4/19) for tilmicosine and 11,3% (7/62) for danofloxacine. For calves suffering from gastrointestinal problems, most frequently Rotavirus (57,6%, 19/33), E. coli (47,7%, 74/155) and Campylobacter spp. (27,7%, 43/155) were found. A resistance against tetracycline was evident for 95,0% (19/20) of all isolated E. coli, and for 80,0% (16/20) in respect to sulfonamides and for 57,1% (12/21) against enrofloxacine. For fatalities with unknown causation, a perforated abomasal ulcer was the most important finding (33,3%, 7/21), followed by diarrhea (28,6%, 6/21) and indigestion related to ruminal acidosis (19,1%, 4/21). The results indicate that aetiological investigations facilitate the evaluation of stock problems. The systematic assessment of abiotic risk factors remains, however, indispensable for the factorial diseases most frequently found on farms raising calves.

Penicillins, cephalosporins and other betalactam antibiotics are widely used antibacterial drugs. Recently it was found that some of them also have effects on proliferating eukaryotic cells (Neftel, K.A. and Hübscher, U. (1987) Antimicrob. Agents Chemother. 31, 1657-1661), and one such effect was shown to be the inhibition of DNA polymerase alpha (Huynh Do,U., Neftel, K.A., Spadari, S. and Hübscher, U. (1987) Nucl. Acids Res. 15, 10495-10506). The data suggested that degradation products of betalactam antibiotics were responsible for the inhibitory effect on DNA polymerase alpha. There is some confirmation at the structural level, since we found that penicillin binding proteins, the natural target of the cephalosporins, share amino-acid homologies to DNA polymerases and also to reverse transcriptase from HIV1 (Hafkemeyer, P., Neftel, K.A. and Hübscher, U. Meth. Find. Exp. Clin. Pharmacol. 12, 43-46, 1990). We have purified and determined the structure of one product from the cephalosporin Ceftazidim and found one molecule (HP 0.35) that did not interfere with eukaryotic cell proliferation but rather had a specific inhibitory effect on the RNase H activity of human immunodeficiency virus 1 (HIV1) and feline immunodeficiency virus (FIV) reverse transcriptases, while the DNA polymerising activity of these enzymes was not affected. RNases H from HeLa cells, calf thymus and Escherichia coli on the other hand were much less affected by HP 0.35. The inhibitory concentration of 50% (IC50) was more than 10 times lower compared to those of all cellular RNases H. We therefore tested the effect of HP 0.35 on in vitro lentivirus infection as exemplified by FIV-infection of CD(4+)-cat lymphocytes in cell culture. Under conditions where cell proliferation was absolutely unaffected, HP 0.35 was able to inhibit FIV-infection in CD(4+)-cat lymphocytes. Moreover, preincubation of these lymphocytes with HP 0.35 rendered the cells completely unsusceptible to FIV-infection. These data suggest that a degradation product of a clinically used betalactam antibiotic might represent an effective inhibitor class for lentiviral RNase H.

The bacterial insertion element IS1 contains two essential open reading frames, insA and insB, arranged in tandem. We have introduced a number of site-specific mutations into the region including the 3'-terminal region of insA, the region between insA and insB, and the ATG codon at the start of insB. Relative transposition activities of mutant and wild-type elements were determined using a modified in vivo cointegration assay. The results support the hypothesis that a translational (-1) frameshift occurring in the 3'-terminal region of insA and linking insB to insA is responsible for the synthesis of the active IS1 transposition enzyme. Further results with IS1 elements containing internal deletions are in agreement with a role of the normally terminated insA product as an inhibitor of transposition.