Journal Article

Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands

Mir, Ignacio, Shrestha, Archana, Campoy, Susana, Barbé, Jordi, Christie, Gail E., Penadés, José R., Lasa, Íñigo, Tormo-Más, María Ángeles, Tallent, Sandra M., Novick, Richard P.

2010

Overview

Moonlighting Toxic shock syndrome is a rare, potentially fatal illness that can be caused by the release of toxins from Staphylococcus bacteria. The toxic particles are encoded by discrete genetic units called pathogenicity islands, which reside passively in the host chromosome, under the control of the global repressor Stl, unless activated by a helper phage. It is now shown that a non-essential and specific protein from the helper phage 80α is responsible for de-repression of the pathogenicity island, thereby providing the mechanism for the first step of its mobilization. The proteins involved are 'moonlighters', because they have two different and genetically distinct activities. Through a remarkable evolutionary adaptation, various related pathogenicity islands co-opt entirely unrelated phage proteins to aid in their mobilization. Staphylococcal superantigens can lead to toxic shock syndrome. They are encoded on pathogenicity islands and with the aid of helper phages can be excised and packaged into highly transmissable phage particles. Here it is shown that a specific, non-essential helper phage protein is responsible for derepression of the pathogenicity island, thereby providing the mechanism for the first step of its mobilization. Staphylococcal superantigen-carrying pathogenicity islands (SaPIs) are discrete, chromosomally integrated units of ∼15 kilobases that are induced by helper phages to excise and replicate. SaPI DNA is then efficiently encapsidated in phage-like infectious particles, leading to extremely high frequencies of intra- as well as intergeneric transfer 1 , 2 , 3 . In the absence of helper phage lytic growth, the island is maintained in a quiescent prophage-like state by a global repressor, Stl, which controls expression of most of the SaPI genes 4 . Here we show that SaPI derepression is effected by a specific, non-essential phage protein that binds to Stl, disrupting the Stl–DNA complex and thereby initiating the excision-replication-packaging cycle of the island. Because SaPIs require phage proteins to be packaged 5 , 6 , this strategy assures that SaPIs will be transferred once induced. Several different SaPIs are induced by helper phage 80α and, in each case, the SaPI commandeers a different non-essential phage protein for its derepression. The highly specific interactions between different SaPI repressors and helper-phage-encoded antirepressors represent a remarkable evolutionary adaptation involved in pathogenicity island mobilization.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/41/2482 / 631/337 / 631/45/612/1256 / Alleles / Amino Acid Sequence / Bacteria / Bacterial proteins / Bacteriology / Biological and medical sciences / Deoxyribonucleic acid / DNA / DNA - biosynthesis / DNA - genetics / DNA Replication / E coli / Ecological adaptation / Fundamental and applied biological sciences. Psychology / Genetic aspects / Genetics / Genomic Islands - genetics / Helper Viruses - enzymology / Helper Viruses - genetics / Helper Viruses - metabolism / Helper Viruses - physiology / Humanities and Social Sciences / Islands / letter / Lysogeny - physiology / Microbiology / Molecular Sequence Data / multidisciplinary / Pathogens / Physiological aspects / Prophages - metabolism / Prophages - physiology / Proteins / Pyrophosphatases - chemistry / Pyrophosphatases - genetics / Pyrophosphatases - metabolism / Recombination, Genetic - genetics / Repressor Proteins - antagonists & inhibitors / Repressor Proteins - genetics / Repressor Proteins - metabolism / Science / Science (multidisciplinary) / Shock, Septic / Staphylococcus / Staphylococcus aureus - genetics / Staphylococcus aureus - pathogenicity / Staphylococcus aureus - virology / Staphylococcus infections / Staphylococcus Phages - enzymology / Staphylococcus Phages - genetics / Staphylococcus Phages - metabolism / Staphylococcus Phages - physiology / Superantigens - genetics / Up-Regulation - genetics / Viral Proteins - chemistry / Viral Proteins - genetics / Viral Proteins - metabolism / Virulence (Microbiology)