Staphylococcus aureus colonizes the human skin, thereby causing various disorders, including eczema. Highly virulent strains that are resistant to multiple antibiotics represent a leading cause of nosocomial infections that are difficult to eradicate, emphasizing the need for alternative treatments. 

Attachment of S. aureus to the skin involves specific bacterial cell surface proteins that bind to target ligands on the outer surface of the epidermis. In a recent study published in Science Advances, research teams from Auburn University, University of Birmingham, and UCLouvain used in vitro and in silico single-molecule force spectroscopy to demonstrate that the staphylococcal serine-aspartate repeat D (SdrD) protein forms ultrastrong bonds with the skin protein desmoglein-1 (DSG-1). 
This is among the strongest non-covalent protein-protein interaction ever reported, explaining why the pathogen remains attached to the skin even after scratching or washing, and helping us understand why these infections are so difficult to get rid of. 

Remarkably, the teams discovered that calcium, an element better known for strengthening bones, plays a key role in fortifying this bacterial grip. 
When calcium levels are reduced, the bond between SdrD and DSG-1 weakens significantly. When calcium is added back, the bond becomes even stronger. This finding is particularly relevant for patients with eczema, where disrupted calcium gradients amplify SdrD interactions, which could potentially intensify S. aureus virulence. 

This study provides crucial insights into the calcium-dependent regulation of pathogen adhesion and opens the door to new strategies for combating antibiotic-resistant infections. Instead of trying to kill bacteria directly, which often drives the evolution of resistance, scientists could design therapies that block or weaken bacterial adhesion.

We are interested in SPO11, an enzyme that catalyses the formation of DNA double strand breaks during meiosis. Although such DNA damages are potentially harmful to the cell, the formation of DNA double-strand breaks by SPO11 is programmed at the beginning of meiosis and is conserved across eukaryotes. These breaks are important because they trigger a DNA repair program by homologous recombination that allow the pairing of parental chromosomes, their proper segregation in daughter cells, and promotes genetic diversity by allelic exchanges.

Now, 28 years after the identification of SPO11, we report the first in vitro reconstitution of its DNA cleavage activity in Nature. 

In mouse, SPO11 forms a topoisomerase like complex with the protein TOP6BL and requires a series of additional partners. Surprisingly, we found that in our assay SPO11 alone was sufficient to catalyse DSB. 

Although SPO11 is monomeric in solution, we demonstrate that it assembles dimers to cleave DNA. A key new insight from this work is that dimerization establishes an inherent limitation to catalysis. We therefore propose that, in vivo, SPO11 is recruited by its partners proteins to increase its local concentration, thereby driving dimerization and cleavage. This model explains how the timing and distribution of meiotic double-strand breaks can be regulated to prevent detrimental DNA damage.