Deletion of biofilm synthesis in Eubacterium limosum ATCC 8486 improves handling and transformation efficiency.

Eubacterium limosum is an acetogenic bacterium of potential industrial relevance for its ability to efficiently metabolize a range of single carbon compounds. However, extracellular polymeric substance (EPS) produced by the type strain ATCC 8486 is a serious impediment to bioprocessing and genetic engineering. To remove these barriers, here we bioinformatically identified genes involved in EPS biosynthesis, and targeted several of the most promising candidates for inactivation, using a homologous recombination-based approach. Deletion of a single genomic region encoding homologues for epsABC, ptkA, and tmkA resulted in a strain incapable of producing EPS. This strain is significantly easier to handle by pipetting and centrifugation, and retains important wild-type phenotypes including the ability to grow on methanol and carbon dioxide and limited oxygen tolerance. Additionally, this strain is also more genetically tractable with a 2-fold increase in transformation efficiency compared to the highest previous reports. This work advances a simple, rapid protocol for gene knockouts in E. limosum using only the native homologous recombination machinery. These results will hasten the development of this organism as a workhorse for valorization of single carbon substrates, as well as facilitate exploration of its role in the human gut microbiota.

Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth?

OBJECTIVE: To evaluate the impact of psychopharmacologic treatments on neuropsychological functioning in bipolar youth. METHOD: Participants were 173 children (aged 6-17 years) with DSM-IV bipolar disorder. Participants were comprehensively assessed using structured diagnostic interviews (Schedule for Affective Disorders and Schizophrenia for School-Age Children) and neuropsychological measures (eg, subtests of the Wechsler Intelligence Scale for Children-III and Wechsler Adult Intelligence Scale-III) during the years 2001-2006. Comparisons were made in neuropsychological functioning between medicated and unmedicated youth with bipolar disorder. RESULTS: Children who were treated with mood stabilizers performed significantly (P < .05) more poorly than untreated children on measures of processing speed and working memory. Treatment with other classes of medication, including second-generation antipsychotics, was not significantly associated with neuropsychological impairments. CONCLUSIONS: Treatment with mood stabilizers may be associated with specific neuropsychological impairments. Cognitive side effects may need to be considered in selecting particular psychopharmacologic treatments for children with bipolar disorder.