Coordinated transcriptional response to environmental stress by a Synechococcus virus.

Viruses are a major control on populations of microbes. Often, their virulence is examined in controlled laboratory conditions. Yet, in nature, environmental conditions lead to changes in host physiology and fitness that may impart both costs and benefits on viral success. Phosphorus (P) is a major abiotic control on the marine cyanobacterium Synechococcus. Some viruses infecting Synechococcus have acquired, from their host, a gene encoding a P substrate binding protein (PstS), thought to improve virus replication under phosphate starvation. Yet, pstS is uncommon among cyanobacterial viruses. Thus, we asked how infections with viruses lacking PstS are affected by P scarcity. We show that the production of infectious virus particles of such viruses is reduced in low P conditions. However, this reduction in progeny is not caused by impaired phage genome replication, thought to be a major sink for cellular phosphate. Instead, transcriptomic analysis showed that under low P conditions, a PstS-lacking cyanophage increased the expression of a specific gene set that included mazG, hli2, and gp43 encoding a pyrophosphatase, a high-light inducible protein and DNA polymerase, respectively. Moreover, several of the upregulated genes were controlled by the host's phoBR two-component system. We hypothesize that recycling and polymerization of nucleotides liberates free phosphate and thus allows viral morphogenesis, albeit at lower rates than when phosphate is replete or when phages encode pstS. Altogether, our data show how phage genomes, lacking obvious P-stress-related genes, have evolved to exploit their host's environmental sensing mechanisms to coordinate their own gene expression in response to resource limitation.

A single sensor controls large variations in zinc quotas in a marine cyanobacterium.

Marine cyanobacteria are critical players in global nutrient cycles that crucially depend on trace metals in metalloenzymes, including zinc for CO2 fixation and phosphorus acquisition. How strains proliferating in the vast oligotrophic ocean gyres thrive at ultra-low zinc concentrations is currently unknown. Using Synechococcus sp. WH8102 as a model we show that its zinc-sensor protein Zur differs from all other known bacterial Zur proteins in overall structure and the location of its sensory zinc site. Uniquely, Synechococcus Zur activates metallothionein gene expression, which supports cellular zinc quotas spanning two orders of magnitude. Thus, a single zinc sensor facilitates growth across pico- to micromolar zinc concentrations with the bonus of banking this precious resource. The resultant ability to grow well at both ultra-low and excess zinc, together with overall lower zinc requirements, likely contribute to the broad ecological distribution of Synechococcus across the global oceans.

A metallothionein from an open ocean cyanobacterium removes zinc from the sensor protein controlling its transcription.

Bacterial metallothioneins are known for a limited range of phyla including cyanobacteria. We have characterised the BmtA from the marine cyanobacterium Synechococcus sp. WH8102 (SynBmtA). This strain inhabits the open ocean, one of the most nutrient-poor environments on Earth, with very low total and free Zn2+ concentrations. Therefore, the presence of a metallothionein, usually associated with zinc and cadmium tolerance, in this strain is intriguing. Previous transcriptomics work revealed that unprecedentedly, expression of SynBmtA is activated by the Synechococcus sp. WH8102 "zinc uptake regulator" (SynZur) at elevated [Zn2+]. SynBmtA binds four Zn2+ ions, and its first 37 residues adopt the zinc-finger fold characteristic of BmtAs. In contrast, sequence similarity to other BmtAs in the C-terminal stretch is low. This is expected to affect especially the most reactive site in zinc-transfer reactions. Indeed, chelators were unable to extract Zn2+ from SynBmtA, even in the presence of denaturant. This indicates an extremely stable protein fold, with no accessibility to any bound zinc ions in the folded protein. In addition, the zinc-binding affinity of SynBmtA exceeds those of any other metallothioneins. Apo-SynBmtA is capable of removing zinc from the sensory site of SynZur, providing one possible avenue of de-activating transcription of the synbmtA gene. All of these properties are consistent with a role in safely sequestering any excess zinc, to prevent toxic effects. The fact that this strain stores zinc in a metallothionein rather than employing an efflux pump implies that zinc is a valuable resource for Synechococcus sp. WH8102 and related strains.

Bacterial zinc uptake regulator proteins and their regulons.

All organisms must regulate the cellular uptake, efflux, and intracellular trafficking of essential elements, including d-block metal ions. In bacteria, such regulation is achieved by the action of metal-responsive transcriptional regulators. Among several families of zinc-responsive transcription factors, the 'zinc uptake regulator' Zur is the most widespread. Zur normally represses transcription in its zinc-bound form, in which DNA-binding affinity is enhanced allosterically. Experimental and bioinformatic searches for Zur-regulated genes have revealed that in many cases, Zur proteins govern zinc homeostasis in a much more profound way than merely through the expression of uptake systems. Zur regulons also comprise biosynthetic clusters for metallophore synthesis, ribosomal proteins, enzymes, and virulence factors. In recognition of the importance of zinc homeostasis at the host-pathogen interface, studying Zur regulons of pathogenic bacteria is a particularly active current research area.