Biomarker candidates for the detection of an infectious etiology of febrile neutropenia.

Purpose: Infections and subsequent septicemia are major complications in neutropenic patients with hematological malignancies. Here, we identify biomarker candidates for the early detection of an infectious origin, and monitoring of febrile neutropenia (FN).

Methods: Proteome, metabolome, and conventional biomarkers from 20 patients with febrile neutropenia without proven infection (FNPI) were compared to 28 patients with proven infection, including 17 patients with bacteremia.

Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts.

Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals.

Histidine degradation via an aminotransferase increases the nutritional flexibility of Candida glabrata.

The ability to acquire nutrients during infections is an important attribute in microbial pathogenesis. Amino acids are a valuable source of nitrogen if they can be degraded by the infecting organism. In this work, we analyzed histidine utilization in the fungal pathogen of humans Candida glabrata.

Structural fine-tuning of a multifunctional cytochrome P450 monooxygenase.

AurH is a unique cytochrome P450 monooxygenase catalyzing the stepwise formation of a homochiral oxygen heterocycle, a key structural and pharmacophoric component of the antibiotic aureothin. The exceptional enzymatic reaction involves a tandem oxygenation process including a regio- and stereospecific hydroxylation, followed by heterocyclization. For the structural and biochemical basis of this unparalleled sequence, four crystal structures of AurH variants in different conformational states and in complex with the P450 inhibitor ancymidol were solved, which represent the first structures of the CYP151A group.

Exploiting enzymatic promiscuity to engineer a focused library of highly selective antifungal and antiproliferative aureothin analogues.

Aureothin is a shikimate-polyketide hybrid metabolite from Streptomyces thioluteus with a rare nitroaryl moiety, a chiral tetrahydrofuran ring, and an O-methylated pyrone ring. The antimicrobial and antitumor activities of aureothin have caught our interest in modulating its structure as well as its bioactivity profile. In an integrated approach using mutasynthesis, biotransformation, and combinatorial biosynthesis, a defined library of aureothin analogues was generated.