Plasmodium Apicoplast Gln-tRNAGln Biosynthesis Utilizes a Unique GatAB Amidotransferase Essential for Erythrocytic Stage Parasites.

The malaria parasite Plasmodium falciparum apicoplast indirect aminoacylation pathway utilizes a non-discriminating glutamyl-tRNA synthetase to synthesize Glu-tRNA(Gln) and a glutaminyl-tRNA amidotransferase to convert Glu-tRNA(Gln) to Gln-tRNA(Gln). Here, we show that Plasmodium falciparum and other apicomplexans possess a unique heterodimeric glutamyl-tRNA amidotransferase consisting of GatA and GatB subunits (GatAB). We localized the P. falciparum GatA and GatB subunits to the apicoplast in blood stage parasites and demonstrated that recombinant GatAB converts Glu-tRNA(Gln) to Gln-tRNA(Gln) in vitro. We demonstrate that the apicoplast GatAB-catalyzed reaction is essential to the parasite blood stages because we could not delete the Plasmodium berghei gene encoding GatA in blood stage parasites in vivo. A phylogenetic analysis placed the split between Plasmodium GatB, archaeal GatE, and bacterial GatB prior to the phylogenetic divide between bacteria and archaea. Moreover, Plasmodium GatA also appears to have emerged prior to the bacterial-archaeal phylogenetic divide. Thus, although GatAB is found in Plasmodium, it emerged prior to the phylogenetic separation of archaea and bacteria.

Opioid Use Disorder Treatment Decision Making And Care Navigation Upon Release From Prison: A Feasibility Study.

PURPOSE: Opioid use disorder (OUD) is a medical condition that is effectively treated with medications. A major challenge in breaking the cycle of OUD and related illegal activity is seamlessly introducing medications for opioid use disorder (MOUD) as individuals leave jail or prison. We examined the feasibility of a pilot intervention to link participants to ongoing MOUD and psychosocial supports following release from custody. METHODS: The study enrolled adults with a history of OUD released from Washington State prisons to Department of Corrections (DOC) community supervision. Participants were randomized to the study intervention or comparison group. The intervention consisted of education on OUD and available treatments, support with individualized treatment decision making, and continued care navigation for 6 months to facilitate linkage to chosen treatments. Participants randomized to the control condition received referral to services in the community from their community corrections officers. A care navigation activity log documented intervention participants' intervention engagement, service utilization, and needs. Follow-up interviews were conducted at 1 and 6 months to assess satisfaction with the intervention. RESULTS: Fifteen participants were enrolled. All were male, most were white (86.6%) and the average age was 36.9 years. The majority (14 of 15 participants) were near-daily heroin users with severe OUD prior to incarceration. Of the seven intervention participants, two wished to start medications immediately. Three participants reported starting buprenorphine or methadone in the subsequent follow-up period, with or without social support and/or outpatient counseling, and three reported enrolling in social support and/or outpatient counseling without medications. Participants who received the intervention reported high satisfaction. We discuss barriers and facilitators to study implementation. CONCLUSION: An intervention to link participants to ongoing MOUD and psychosocial supports following release from prison had broad acceptability among participants and was feasible to implement among those recruited; however, enrollment was much lower than anticipated and the study intervention did not demonstrate the intended effect to facilitate use of MOUD immediately post-release in this small sample of participants. Given recent research showing benefits of pre-release medication initiation, the potential added benefits of this two-part intervention should be studied in systems that initiate MOUD prior to release.