Probing the ligand preferences of the three types of bacterial pantothenate kinase.

Pantothenate kinase (PanK) catalyzes the transformation of pantothenate to 4'-phosphopantothenate, the first committed step in coenzyme A biosynthesis. While numerous pantothenate antimetabolites and PanK inhibitors have been reported for bacterial type I and type II PanKs, only a few weak inhibitors are known for bacterial type III PanK enzymes. Here, a series of pantothenate analogues were synthesized using convenient synthetic methodology. The compounds were exploited as small organic probes to compare the ligand preferences of the three different types of bacterial PanK. Overall, several new inhibitors and substrates were identified for each type of PanK.

Small Molecule Restores Itaconate Sensitivity in Salmonella enterica: A Potential New Approach to Treating Bacterial Infections.

In the context of increasing global antibiotic resistance, the need for alternative therapeutic targets is great. Although new antibiotics and resistance inhibitors provide temporary solutions, they are bound to become obsolete. In this work, we propose a new approach, coined "bacterio-modulation" that aims to restore macrophage potency towards bacterial strains that are able to survive in phagolysosomes. One key defense in the macrophage's arsenal is itaconate, an endogenous molecule with antimicrobial activity. Some intracellular pathogens have evolved to produce itaconate-degrading enzymes, which are required for intracellular proliferation and to promote pathogenicity. We herein present the first molecule able to resensitize Salmonella enterica to itaconate.

Effect of Exposure to Gun Violence in Video Games on Children's Dangerous Behavior With Real Guns: A Randomized Clinical Trial.

Importance: Among resource-rich countries, the United States has the highest rate of child mortality by unintentional firearm use. Objective: To test whether children's exposure to violent video games increases dangerous behavior around firearms. Design, Setting, and Participants: This randomized clinical trial was set in a university laboratory and included pairs of children aged 8 to 12 years who knew each other. Of 313 participants who signed up, 250 were tested (2 arrived without partners, 61 did not arrive to participate). Of the 250 children tested, 8 were excluded (2 did not complete the study, 2 had participated in a related study, and 4 were outliers). Each child was paid $25. Data were collected July 1, 2017, to July 31, 2018. Interventions: In a 3-group randomized design, pairs of children played or watched 1 of 3 versions of the game Minecraft for 20 minutes: (1) violent with guns, (2) violent with swords, or (3) nonviolent. The pairs of children were then placed in a different room and were told they could play with toys and games for 20 minutes. A cabinet in the room contained 2 hidden disabled handguns with counters for trigger pulls. Play sessions were videotaped. Main Outcomes and Measures: Main outcomes were touching a handgun, seconds spent holding a handgun, and number of trigger pulls (including at oneself or the partner). Control variables included sex, age, trait aggressiveness, exposure to violent media, attitudes toward guns, presence of firearms in the home, interest in firearms, and whether the child had taken a firearm safety course. Results: Of 242 participants, 220 children (mean [SD] age, 9.9 [1.4] years; 129 [58.6%] boys) found a gun and were included in analysis. Among the 76 children who played the video game that included gun violence, 47 children (61.8%) touched a handgun. Among the 74 children who played the video game that included sword violence, 42 (56.8%) touched a handgun. Among the 70 children who played the nonviolent video game, 31 (44.3%) touched a handgun. Participants who played a violent version of the game were more likely to shoot at themselves or their partners than those who played a nonviolent game. Other risk factors for dangerous behavior around firearms included self-reported habitual exposure to violent media and trait aggressiveness. Self-reported exposure to violent media was positively associated with total trigger pulls (incidence rate ratio [IRR], 1.40; 95% CI, 1.00-1.98) and trigger pulls at oneself or one's partner (IRR, 1.88; 95% CI, 1.29-2.72). Trait aggression was positively associated with total trigger pulls (IRR, 13.52; 95% CI, 3.14-58.29), trigger pulls at oneself or one's partner (IRR, 25.69; 95% CI, 5.92-111.39), and time spent holding a handgun (IRR, 4.22; 95% CI, 1.62-11.02). One protective factor was having taken a firearm safety training course. Conclusions and Relevance: Exposure to violent video games increases children's dangerous behavior around firearms. Trial Registration: ClinicalTrials.gov identifier NCT03259139.