Biology subjects

Powell, L. M.

Publications and source records attributed to Powell, L. M..

4 recordsLinked to original sources

bioRxiv2023

Prevalence of Erythromycin Resistant emm92-type Invasive Group A Streptococcal Infections in West Virginia, United States, 2021-2023

BackgroundIncreasing incidence of invasive group A Streptococcus (iGAS) disease has been reported in Europe and United States over the past several years. Coupled with this are observations of higher rates of resistance to non-beta lactam antimicrobials. ObjectivesThe aim of this study was to characterize iGAS and pharyngitis isolates from West Virginia (WV), a region outside of the US national active bacteria core surveillance purview, where risk factors associated with iGAS infections are prevalent. MethodsSeventy-seven invasive group A Streptococcus isolates were collected from sixty-seven unique patients at the J.W. Ruby Memorial Hospital Clinical Microbiology Laboratory in WV from 2021-23. Invasive isolates and twenty unique pharyngitis isolates were tested for clindamycin and erythromycin susceptibilities in the clinical laboratory. Patient demographic and clinical information was retrieved from patient electronic health records. Isolates were further characterized based on emm-type and detection of MLSB resistance determinants. ResultsTwenty-six (39%) isolates were of a single emm-type, emm92. All emm92 isolates were uniformly erythromycin/clindamycin resistant with inducible or constitutive MLSB resistance imparted by the plasmid-borne erm(T) gene. The majority of emm92 infections were associated with adult patients who reported intravenous drug use, whereas no pharyngitis infections were caused by an emm92 strain. Overall, fifty-one (76%) of the sixty-seven iGAS isolates were determined to carry MLSB resistance. ConclusionsIsolates of emm-type 92 predominated in this collection, were uniformly erythromycin/clindamycin resistant, and were associated with adult intravenous drug use but not with pediatric pharyngitis.

microbiology↗

bioRxiv2022

Emergence of Erythromycin Resistant Invasive Group A Streptococcus in West Virginia, United States

Combination therapy with penicillin and clindamycin has been a mainstay for treatment of invasive group A Streptococcus (iGAS) infections yet increasing macrolide resistance may limit such treatment for strains displaying MLSB phenotypes. The CDC recently reported erythromycin and clindamycin resistance rates for iGAS exceeding 20% in 2017. Here, we investigated 76 iGAS isolates from 66 patients identified at J.W. Ruby Memorial Hospital in West Virginia from 2020-2021. emm typing was performed using the CDC protocol and database. Resistance genes were detected by PCR and sequencing, whereas antimicrobial susceptibility testing was performed in clinical and research laboratories with standard techniques. Median patient age was 42 years (23-86 range). 76% (n=50) of isolates were simultaneously resistant to erythromycin and clindamycin, which included both inducible (n=40) and constitutive (n=9) resistance. All emm92 (n=35) and emm11 (n=8) isolates were erythromycin resistant, while the remaining 11% (n=7) of resistant isolates comprised 5 emm types. Susceptible isolates primarily included emm89 (n=6) iGAS. Macrolide resistance was conferred by the plasmid-borne ermT gene in all emm92 isolates and by chromosomally-encoded ermA (n=7), ermB (n=7), and mefA (n=1) in other emm types. Macrolide-resistant iGAS were typically resistant to tetracycline and aminoglycoside antibiotics. Here, we characterized iGAS infections affecting non-pediatric residents across West Virginia. We showed a shift in emm-type distribution compared to historical and national reports, and dominance of macrolide-resistant isolates which raises concern for emerging resistance to commonly-prescribed antibiotics used in treatment of iGAS infections.

microbiology↗

bioRxiv2020

A RIF1 and KAP1-based, double-bookmarking system generates a toggle switch that stabilises the identities of the active and inactive X chromosomes during random X inactivation in mouse

The onset of random X inactivation in mouse requires the switch from a symmetric to an asymmetric state, where the identities of the future inactive and active X chromosomes are assigned. Here we show that RIF1 and KAP1 are two fundamental factors for the definition of the asymmetry. Our data show that at the onset of mESC differentiation, upregulation of the long non-coding RNA Tsix weakens the symmetric RIF1 association with the Xist promoter, and opens a window of opportunity for a more stable association of KAP1. KAP1 is required to sustain high levels of Tsix, thus reinforcing and propagating the asymmetry, and, as a result, marking the future active X chromosome. Furthermore, we show that RIF1 association with the future inactive X chromosome is essential for Xist upregulation. This double-bookmarking system, based on the mutually exclusive relationships of Tsix and RIF1, and RIF1 and KAP1, thus coordinates the identification of the inactive and active X chromosomes and initiates a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X chromosome state.

molecular biology↗

bioRxiv2019

Atoh1 is repurposed from neuronal to hair cell determinant by Gfi1 acting as a coactivator without redistribution of its genomic binding sites

Although the lineage-determining ability of transcription factors is often modulated according to cellular context, the mechanisms by which such switching occurs are not well known. Using a transcriptional programming model, we found that Atoh1 is repurposed from a neuronal to an inner ear hair cell (HC) determinant by the combined activities of Gfi1 and Pou4f3. In this process, Atoh1 maintains its regulation of neuronal genes but gains ability to regulate HC genes. Pou4f3 enables Atoh1 access to genomic locations controlling the expression of sensory (including HC) genes, but Atoh1+Pou4f3 are not sufficient for HC differentiation. Gfi1 is key to the Atoh1-induced lineage switch, but surprisingly does not alter Atoh1s binding profile. Gfi1 acts in two divergent ways. It represses the induction by Atoh1 of genes that antagonise HC differentiation, a function in keeping with its well-known repressor role in haematopoiesis. Remarkably, we find that Gfi1 also acts as a co-activator: it binds directly to Atoh1 at existing target genes to enhance its activity. These findings highlight the diversity of mechanisms by which one TF can redirect the activity of another to enable combinatorial control of cell identity.

developmental biology↗