There has been an increase in number of human infections by mycobacteria and opportunistic pathogens of the closely related nocardioform bacteria. Frequent multiple drug resistance in these organisms makes it desirable to identify novel targets for antimicrobial agents. Bacteriophages offer one way to do this as analysis of their DNA reveals great diversity in their genetic makeup, suggesting variety in the way they interfere with host cells. Four novel nocardiophages were therefore isolated from soil and characterized. Libraries of their nucleic acid were constructed and screened for clones inhibitory to a nocardioform of the genus Rhodococcus. Nine clones were characterized, and minimum necessary DNA for inhibitory activity sequenced. Of 18 ORFs predicted on these DNAs, 13 could not be assigned a function. Genes similar to ones in databases apparently interfered with DNA metabolism, protein synthesis, or integrity of plasma membrane. This genetic approach may be an efficient and effective way to discover novel targets for antibiotics.

Two types of placentitis were studied: ascending and nocardioform placentitis. Although the first diagnosis of nocardioform placentitis was made three decades ago, little is known about the disease, due to the lack of an experimental model. In attempt to develop a research model, Crossiela equi was inoculated through intrauterine, intravenous, intrapharyngeal, and oral routes, but none of the routes resulted in nocardioform placentitis. This may indicate that unidentified factors may play a role in disease pathogenesis and that simple presence of bacteria is not sufficient to induce nocardioform placentitis. The second and major component of this dissertation involved the identification of diagnostic markers for placentitis. Because ascending bacterial placentitis is readily and predictably induced using existing experimental models, this model was used to identify diagnostic markers for placentitis in maternal plasma and fetal fluids. Three potential biomarkers were examined: acute phase inflammatory proteins, steroid hormones produced by the fetoplacental unit, and protein composition of the fetal fluids. Of the three acute phase proteins investigated, serum amyloid A and haptoglobin but not fibrinogen increased in association with experimentally induced ascending placentitis. Androgens and progestins appear to be poor markers for placentitis. Serum estradiol 17β concentrations were reduced in mares with experimentally induced placentitis and appear to be a good marker for placentitis in mares. Different methods were used to study the protein composition of the fetal fluids. Alpha-fetoprotein was characterized as a major protein present in the equine fetal fluids, and this protein was elevated in plasma of mares with placentitis. In another study, using a high-throughput proteomic technique several new proteins were characterized in the amniotic and allantoic fluids of mares carrying normal pregnancies, and several previously uncharacterized proteins were detected in the allantoic fluid of mares with placentitis. Three secreting proteins were elevated in allantoic fluid of mares with experimentally induced ascending placentitis.