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The domestication of cattle provided Propionibacteriaceae the opportunity to adapt to human skin. These bacteria constitute a distinct genus ( Cutibacterium ), and a single species within that genus ( C. acnes ) dominates 25% of human skin. C. acnes protects humans from pathogen colonization, but it can also infect indwelling medical devices inserted through human skin. Proteins that help Cutibacteria live on our skin may also act as virulence factors during an opportunistic infection, like a shoulder periprosthetic joint infection (PJI). To better understand the evolution of this commensal and opportunistic pathogen, we sought to extensively characterize one of these proteins, RoxP. This secreted protein is only found in the Cutibacterium genus, helps C. acnes grow in oxic environments, and is required for C. acnes to colonize human skin. Structure-based sequence analysis of twenty-one RoxP orthologs (71-100% identity to C. acnes strain KPA171202 RoxP_1) revealed a high-degree of molecular surface conservation and helped identify a potential heme-binding interface. Biophysical evaluation of a subset of seven RoxP orthologs (71-100% identity) demonstrated that heme-binding is conserved. Computational modeling of these orthologs suggests that RoxP heme-binding is mediated by an invariant molecular surface composed of a surface-exposed tryptophan (W66), adjacent cationic pocket, and nearby potential heme axial ligands. Further, these orthologs were found to undergo heme-dependent oligomerization. To further probe the role of this protein in C. acnes biology, we developed four monoclonal anti-RoxP antibodies, assessed the binding of those antibodies to a subset of ten RoxP orthologs (71-100% identity), developed an anti-RoxP sandwich ELISA (sELISA) with sub-nanogram sensitivity, and adapted that sELISA to quantitate RoxP in human biofluids that can be infected by C. acnes (serum, synovial fluid, cerebrospinal fluid). This study expands our understanding of how an environmental bacterium evolved to live on humans, and the assays developed in this work can now be used to identify this organism when it gains access to sterile sites to cause opportunistic infections., Author Summary: The longer humans live, the more they require internal "replacement parts," like prosthetic joints. Increased placement of these and other medical devices has increased their complications, which frequently are infections caused by microbes that live on humans. One of these microbes is Cutibacterium acnes , which dominates 25% of human skin. It appears that when humans domesticated cattle, a C. acnes ancestor adapted from living in cows to living on people. One of these adaptations was RoxP, a protein only found in Cutibacterium and carried by all C. acnes . Here, we describe our extensive characterization of RoxP. We found that distantly related RoxP conserve high stability at the low pH found on human skin. They also conserve the ability to bind heme, a source of iron used by microbes when they infect humans. As a part of this work, we developed tests that measure RoxP to identify C. acnes growth. In a clinic or hospital, these tests could allow a doctor to rapidly identify C. acnes infections, which would improve patient outcomes and lower healthcare costs. This work has helped us better understand how C. acnes adapted to live on humans and to identify C. acnes infections of medical devices.

Organophosphorus (OP) nerve agents and pesticides present significant threats to civilian and military populations. OP compounds include the nefarious G and V chemical nerve agents, but more commonly, civilians are exposed to less toxic OP pesticides, resulting in the same negative toxicological effects and thousands of deaths on an annual basis. After decades of research, no new therapeutics have been realized since the mid-1900s. Upon phosphylation of the catalytic serine residue, a process known as inhibition, there is an accumulation of acetylcholine (ACh) in the brain synapses and neuromuscular junctions, leading to a cholinergic crisis and eventually death. Oxime nucleophiles can reactivate select OP-inhibited acetylcholinesterase (AChE). Yet, the fields of reactivation of AChE and butyrylcholinesterase encounter additional challenges as broad-spectrum reactivation of either enzyme is difficult. Additional problems include the ability to cross the blood brain barrier (BBB) and to provide therapy in the central nervous system. Yet another complication arises in a competitive reaction, known as aging, whereby OP-inhibited AChE is converted to an inactive form, which until very recently, had been impossible to reverse to an active, functional form. Evaluations of uncharged oximes and other neutral nucleophiles have been made. Non-oxime reactivators, such as aromatic general bases and Mannich bases, have been developed. The issue of aging, which generates an anionic phosphylated serine residue, has been historically recalcitrant to recovery by any therapeutic approach-that is, until earlier this year. Mannich bases not only serve as reactivators of OP-inhibited AChE, but this class of compounds can also recover activity from the aged form of AChE, a process referred to as resurrection. This review covers the modern efforts to address all of these issues and notes the complexities of therapeutic development along these different lines of research., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new and powerful active anode system that can be operated in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) has been discovered. In HFIP the molybdenum anode forms a compact, conductive, and electroactive layer of higher-valent molybdenum species. This system can replace powerful but stoichiometrically required Mo V reagents for the dehydrogenative coupling of aryls. This electrolytic reaction is more sustainable and allows the conversion of a broad scope of activated arenes., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)