acil and 20 mM uridine which suggested that exogenous nucleotides were required for capsule synthesis. Post induction, complement strains developed capsules with comparable size as that of wild type as expected. assay where we took standard aliquots of cells from the capsule inducing media after 24 and 48 hours of incubation and plated them on YPD agar. SKI-II web Results showed that ura2 mutant cells were viable in the capsule inducing media thereby attributing its acapsular phenotype to a synthesis defect. Nucleotide PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19650784 Synthesis Inhibition Renders C. albicans More Sensitive to AmB Once the increased efficacy of AmB was demonstrated in conditions of impaired nucleotide synthesis in C. neoformans, we wanted to investigate if this enhanced antifungal effect was consistent in other pathogenic fungi. C. albicans is the causative agent of oral thrush, vulvo-vaginal candidiasis and nosocomial disseminated candidiasis. To evaluate the effect of AmB when pyrimidine synthesis was inhibited in C. albicans, we performed Etest wild type strain SC5314 and a ura2 derivative strain CAI-4. As demonstrated in Drug AmB alone AmB in combination 5-FC alone 5-FC in combination FIC index = MICA’/MICA+MICB’/MICB Interaction Replicate 1 1.56 1.56 100 100 2.0 Indifference Replicate 2 1.56 1.56 100 100 2.0 Indifference Replicate 3 3.125 1.56 100 100 1.5 Indifference AmB: Amphotericin B, 5-FC: 5-Flourocytosine. MICs of AmB and 5-FC alone and in combination against A. fumigatus in 3 separate experiments and calculated FIC values. doi:10.1371/journal.pone.0087246.t004 10 Nucleotide Biosynthesis and Amphotericin B GMP biosynthesis by MPA also increased sensitivity to AmB, reducing the MIC by nearly three-fold. The addition of exogenous 20 mM uracil and 20 mM uridine both restored the wild type MIC levels in the C. albicans ura2 mutant which demonstrates that this supplementation is enough to compensate for the effect of AmB sensitivity which is in contrast to C. neoformans as we saw in Nucleotide Synthesis Inhibition has No Effect on the Susceptibility of A. fumigatus to AmB A. fumigatus is another well-known fungal pathogen against which AmB is used, and is the predominant mold pathogen of humans. To investigate whether the efficacy of the AmB was altered when nucleotide synthesis was inhibited, we performed E-test with wild type strain of A. fumigatus using a combination of AmB and MPA. Kaposi’s sarcoma was first described by Moritz Kaposi in 1872. Over a century and a half later, a substantial increase in patients presenting with KS in New York and Los Angeles heralded the beginning of the AIDS pandemic and led to the discovery of KS-associated herpesvirus as the etiologic agent of the disease. KS is one of three known AIDS-associated malignancies caused by KSHV, with primary effusion lymphoma and multicentric Castleman’s disease being the other two. KS is not only an AIDS-defining cancer; it is also the most common AIDS-associated cancer. KS is classified into 4 clinical forms: classical, endemic, iatrogenic and epidemic AIDS-associated that are histologically indistinguishable and are characterized into: patch, plaque and nodular, with the acceptance that these morphologies represent a continuum and not necessarily distinct entities. Histologically, the tumor is composed of inflammatory infiltrates, KSHVinfected cells of spindle morphology, and aberrant angiogenesis with extravasated red blood cells in slit-like spaces. The origin of the spindle cell continues to be an