Biology subjects

Mikołajczyk, J.

Publications and source records attributed to Mikołajczyk, J..

2 recordsLinked to original sources

bioRxiv2024

The role of two major nucleoid associated proteins in Streptomyces, HupA and HupS, in stress survival and gene expression regulation

Streptomyces are sporulating soil bacteria with enormous potential for secondary metabolites biosynthesis. Regulatory networks governing Streptomyces coelicolor differentiation and secondary metabolites production are complex and composed of numerous regulatory proteins ranging from specific transcriptional regulators to sigma factors. Nucleoid associated proteins (NAPs) are also believed to contribute to regulation of gene expression. Upon DNA binding these proteins impact DNA accessibility. Among NAPs HU proteins are the most widespread and abundant. Unlike other bacteria, the Streptomyces genome encodes two HU homologs: HupA and HupS, differing in structure and expression profile. In this study, we explore whether HupA and HupS affect S. coelicolor growth under optimal and stressful conditions and how they control global gene expression. By testing both single and double mutants we address the question of both HU homologs complementarity. The lack of both hup genes led to growth and sporulation inhibition, as well as increased spore fragility. Our data indicate a synergy between the functions of HupA and HupS during S. coelicolor growth. We also demonstrate, that both HU homologs can be considered global transcription regulators influencing expression of numerous genes encoding proteins linked to chromosome topology, secondary metabolites production and transcription. We identify the independent HupA and HupS regulons as well as genes under the control of both HupA and HupS proteins. Our data indicate some extent of redundancy as well as independent function of both homologs. ImportanceStreptomyces belong to the bacterial family widely used in the production of antibiotics as well as research for new bioactive substances with antimicrobial properties. Gene expression in Streptomyces, and consequently the production of secondary metabolites, is controlled by a vast and complex network of transcriptional regulators. Our data indicate that two proteins, HupA and HupS, involved in the maintenance of chromosome structure, also participate in this regulatory network. Their presence appears to important for S. coelicolors adaptation for survival in unfavorable conditions such as high temperature. The lack of one or both HU proteins affects the expression of many genes, indicating that they act as global transcriptional regulators.

microbiology↗

bioRxiv2021

Global chromosome topology and the two-component systems in concerted manner regulate transcription in Streptomyces

Bacterial gene expression is controlled at multiple levels, with chromosome supercoiling being one of the most global regulators. Global DNA supercoiling is maintained by the orchestrated action of topoisomerases. In Streptomyces, mycelial soil bacteria with a complex life cycle, topoisomerase I depletion led to elevated chromosome supercoiling, changed expression of significant fraction of genes, delayed growth and blocked sporulation. To identify supercoiling-induced sporulation regulators, we searched for S. coelicolor transposon mutants that were able to restore sporulation despite high chromosome supercoiling. We established that transposon insertion in genes encoding a novel two-component system named SatKR reversed the sporulation blockage resulting from topoisomerase I depletion. Transposition in satKR abolished the transcriptional induction of the genes within the so-called supercoiling-hypersensitive cluster (SHC). Moreover, we found that activated SatR also induced the same set of SHC genes under normal supercoiling conditions. We determined that the expression of genes in this region impacted S. coelicolor growth and sporulation. Interestingly, among the associated products is another two-component system (SitKR), indicating the potential for cascading regulatory effects driven by the SatKR and SitKR two-component systems. Thus, we demonstrated the concerted activity of chromosome supercoiling and a hierarchical two-component signalling system that impacts gene activity governing Streptomyces growth and sporulation. IMPORTANCEStreptomyces, soil bacteria with complex life cycle, are the producers of a broad range of biologically active compounds (e.g. antibiotics). Streptomyces respond to various environmental signals using complex transcriptional regulation mechanism. Understanding regulation of their gene expression is crucial for Streptomyces application as industrial organisms. Here, based on extensive transcriptomics analyses, we describe the concerted regulation of genes crucial for growth and development by global DNA supercoiling and novel two-component system. Our data indicate that regulated genes encode growth and sporulation regulator. Thus, we demonstrate that Streptomyces link the global regulatory strategies to adjusts life cycle to unfavourable conditions.

genomics↗