Antibiotic resistance among clinical Ureaplasma isolates from Cuban individuals between 2013 and 2018.

Introduction. Acquired resistance against the antibiotics that are active against Ureaplasma species has been described.Hypothesis/Gap Statement. Diagnostics combined with antimicrobial sensitivity testing are required for therapeutic guidance.Aim. To report the prevalence of antimicrobial resistance among Cuban Ureaplasma isolates and the related molecular mechanisms of resistance.Methodology. Traditional broth microdilution assays were used for antimicrobial sensitivity testing in 262 clinical Ureaplasma species isolates from Cuban patients between 2013 and 2018, and a subset of samples were investigated in parallel with the commercial MYCO WELL D-ONE rapid culture diagnostic assay. The underlying molecular mechanisms for resistance were determined by PCR and sequencing for all resistant isolates.Results. Among the tested isolates, the tetracycline and erythromycin resistance rates were 1.9 and 1.5%, respectively, while fluoroquinolone resistance was not found. The tet(M) gene was found in all tetracycline-resistant isolates, but also in two tetracycline-susceptible Ureaplasma clinical isolates. We were unable to determine the underlying mechanism of erythromycin resistance. The MYCO WELL D-ONE kit overestimated tetracycline and erythromycin resistance in Ureaplasma spp. isolates.Conclusions. Although low levels of antibiotic resistance were detected in Cuban patients over a 5-year period, continued surveillance of the antibiotic susceptibility of Ureaplasma is necessary to monitor possible changes in resistance patterns.

A psychiatric disease-related circular RNA controls synaptic gene expression and cognition.

Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about their potential involvement in brain function and psychiatric disease. Here, we show that circHomer1a, a neuronal-enriched circRNA abundantly expressed in the frontal cortex, derived from Homer protein homolog 1 (HOMER1), is significantly reduced in both the prefrontal cortex (PFC) and induced pluripotent stem cell-derived neuronal cultures from patients with schizophrenia (SCZ) and bipolar disorder (BD). Moreover, alterations in circHomer1a were positively associated with the age of onset of SCZ in both the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). No correlations between the age of onset of SCZ and linear HOMER1 mRNA were observed, whose expression was mostly unaltered in BD and SCZ postmortem brain. Using in vivo circRNA-specific knockdown of circHomer1a in mouse PFC, we show that it modulates the expression of numerous alternative mRNA transcripts from genes involved in synaptic plasticity and psychiatric disease. Intriguingly, in vivo circHomer1a knockdown in mouse OFC resulted in specific deficits in OFC-mediated cognitive flexibility. Lastly, we demonstrate that the neuronal RNA-binding protein HuD binds to circHomer1a and can influence its synaptic expression in the frontal cortex. Collectively, our data uncover a novel psychiatric disease-associated circRNA that regulates synaptic gene expression and cognitive flexibility.

Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics.

The ability of small secretory microvesicles known as exosomes to influence neuronal and glial function via their microRNA (miRNA) cargo has positioned them as a novel and effective method of cell-to-cell communication. However, little is known about the role of exosome-secreted miRNAs in the regulation of glutamate receptor gene expression and their relevance for schizophrenia (SCZ) and bipolar disorder (BD). Using mature miRNA profiling and quantitative real-time PCR (qRT-PCR) in the orbitofrontal cortex (OFC) of SCZ (N = 29; 20 male and 9 female), BD (N = 26; 12 male and 14 female), and unaffected control (N = 25; 21 male and 4 female) subjects, we uncovered that miR-223, an exosome-secreted miRNA that targets glutamate receptors, was increased at the mature miRNA level in the OFC of SCZ and BD patients with positive history of psychosis at the time of death and was inversely associated with deficits in the expression of its targets glutamate ionotropic receptor NMDA-type subunit 2B (GRIN2B) and glutamate ionotropic receptor AMPA-type subunit 2 (GRIA2). Furthermore, changes in miR-223 levels in the OFC were positively and negatively correlated with inflammatory and GABAergic gene expression, respectively. Moreover, miR-223 was found to be enriched in astrocytes and secreted via exosomes, and antipsychotics were shown to control its cellular and exosomal localization in a cell-specific manner. Furthermore, addition of astrocytic exosomes in neuronal cultures resulted in a significant increase in miR-223 expression and a notable reduction in Grin2b and Gria2 mRNA levels, which was strongly inversely associated with miR-223 expression. Lastly, inhibition of astrocytic miR-223 abrogated the exosomal-mediated reduction in neuronal Grin2b expression. Taken together, our results demonstrate that the exosomal secretion of a psychosis-altered and glial-enriched miRNA that controls neuronal gene expression is regulated by antipsychotics.