In the human fungal pathogen Cryptococcus neoformans, sex can benefit its pathogenicity through production of meiospores, which are believed to offer both physical and meiosis-created lineage advantages for its infections. Cryptococcus sporulation occurs following two parallel events, meiosis and differentiation of the basidium, the characteristic sexual structure of the basidiomycetes. However, the circuit integrating these events to ensure subsequent sporulation is unclear. Here, we show the spatiotemporal coordination of meiosis and basidial maturation by visualizing event-specific molecules in developing basidia defined by a quantitative approach. Monitoring of gene induction timing together with genetic analysis reveals co-regulation of the coordinated events by a shared regulatory program. Two RRM family regulators, Csa1 and Csa2, are crucial components that bridge meiosis and basidial maturation, further determining sporulation. We propose that the regulatory coordination of meiosis and basidial development serves as a determinant underlying the production of infectious meiospores in C. neoformans.

Background: Nikkomycins are a group of peptidyl nucleoside antibiotics produced by Streptomyces ansochromogenes. They are competitive inhibitors of chitin synthase and show potent fungicidal, insecticidal, and acaricidal activities. Nikkomycin X and Z are the main components produced by S. ansochromogenes. Generation of a high-producing strain is crucial to scale up nikkomycins production for further clinical trials. Results: To increase the yields of nikkomycins, an additional copy of nikkomycin biosynthetic gene cluster (35 kb) was introduced into nikkomycin producing strain, S. ansochromogenes 7100. The gene cluster was first reassembled into an integrative plasmid by Red/ET technology combining with classic cloning methods and then the resulting plasmid(pNIK)was introduced into S. ansochromogenes by conjugal transfer. Introduction of pNIK led to enhanced production of nikkomycins (880 mg L^-1, 4 -fold nikkomycin X and 210 mg L^-1, 1.8-fold nikkomycin Z) in the resulting exconjugants comparing with the parent strain (220 mg L^-1 nikkomycin X and 120 mg L^-1 nikkomycin Z). The exconjugants are genetically stable in the absence of antibiotic resistance selection pressure. Conclusion: A high nikkomycins producing strain (1100 mg L^-1 nikkomycins) was obtained by introduction of an extra nikkomycin biosynthetic gene cluster into the genome of S. ansochromogenes. The strategies presented here could be applicable to other bacteria to improve the yields of secondary metabolites.

Recent developments of therapeutic agents based on transition metals have attracted a great deal of attention. Metal drugs have advantages over other small molecule drugs, and it was demonstrated that, in a number of studies, they played an important role in pharmaceutical chemical research and clinical chemotherapy of cancers. It is worthwhile mentioning that octahedral polypyridyl ruthenium(II) complexes have shown remarkable applications in chemical biology and medicinal chemistry over the last decade. However, only very recently has there been comprehensive interest in their antimicrobial properties due to metal-related toxic concerns or neglected potential roles in microbiological systems. Our review will highlight the recent developments in octahedral polypyridyl ruthenium(III) complexes that have exhibited significant antimicrobial activities and will discuss the relationship between the chemical structure and biological process of ruthenium complexes, in both bacterial and fungal cells.