ABSTRACT
Magnetic fluctuations induced by geometric frustration of local Ir-spins disturb the formation of long-range magnetic order in the family of pyrochlore iridates. As a consequence, Pr2Ir2O7 lies at a tuning-free antiferromagnetic-to-paramagnetic quantum critical point and exhibits an array of complex phenomena including the Kondo effect, biquadratic band structure, and metallic spin liquid. Using spectroscopic imaging with the scanning tunneling microscope, complemented with machine learning, density functional theory and theoretical modeling, we probe the local electronic states in Pr2Ir2O7 and find an electronic phase separation. Nanoscale regions with a well-defined Kondo resonance are interweaved with a non-magnetic metallic phase with Kondo-destruction. These spatial nanoscale patterns display a fractal geometry with power-law behavior extended over two decades, consistent with being in proximity to a critical point. Our discovery reveals a nanoscale tuning route, viz. using a spatial variation of the electronic potential as a means of adjusting the balance between Kondo entanglement and geometric frustration.
ABSTRACT
Obstacles to bacterial survival and replication in the cytosol of host cells, and the mechanisms used by bacterial pathogens to adapt to this niche are not well understood. Listeria monocytogenes is a well-studied Gram-positive foodborne pathogen that has evolved to invade and replicate within the host cell cytosol; yet the mechanisms by which it senses and responds to stress to survive in the cytosol are largely unknown. To assess the role of the L. monocytogenes penicillin-binding-protein and serine/threonine associated (PASTA) kinase PrkA in stress responses, cytosolic survival and virulence, we constructed a ΔprkA deletion mutant. PrkA was required for resistance to cell wall stress, growth on cytosolic carbon sources, intracellular replication, cytosolic survival, inflammasome avoidance and ultimately virulence in a murine model of Listeriosis. In Bacillus subtilis and Mycobacterium tuberculosis, homologues of PrkA phosphorylate a highly conserved protein of unknown function, YvcK. We found that, similar to PrkA, YvcK is also required for cell wall stress responses, metabolism of glycerol, cytosolic survival, inflammasome avoidance and virulence. We further demonstrate that similar to other organisms, YvcK is directly phosphorylated by PrkA, although the specific site(s) of phosphorylation are not highly conserved. Finally, analysis of phosphoablative and phosphomimetic mutants of YvcK in vitro and in vivo demonstrate that while phosphorylation of YvcK is irrelevant to metabolism and cell wall stress responses, surprisingly, a phosphomimetic, nonreversible negative charge of YvcK is detrimental to cytosolic survival and virulence in vivo. Taken together our data identify two novel virulence factors essential for cytosolic survival and virulence of L. monocytogenes. Furthermore, our data demonstrate that regulation of YvcK phosphorylation is tightly controlled and is critical for virulence. Finally, our data suggest that yet to be identified substrates of PrkA are essential for cytosolic survival and virulence of L. monocytogenes and illustrate the importance of studying protein phosphorylation in the context of infection.
