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2. COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

Author

Szubert, Alex J., Pollock, Katrina M., Cheeseman, Hannah M., Alagaratnam, Jasmini, Bern, Henry, Bird, Olivia, Boffito, Marta, Byrne, Ruth, Cole, Tom, Cosgrove, Catherine A., Faust, Saul N., Fidler, Sarah, Galiza, Eva, Hassanin, Hana, Kalyan, Mohini, Libri, Vincenzo, McFarlane, Leon R., Milinkovic, Ana, O'Hara, Jessica, Owen, David R., Owens, Daniel, Pacurar, Mihaela, Rampling, Tommy, Skene, Simon, Winston, Alan, Woolley, James, Yim, Yee Ting N., Dunn, David T., McCormack, Sheena, and Shattock, Robin J.

Published
2023
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3. Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial

Author

Adams, Kirsty, Amini, Fahimah, Atako, Nafisah B, Bakri, Amalina, Barclay, Wendy, Brodnicki, Elizabeth, Brown, Jonathan C, Byrne, Ruth, Chilvers, Rowena, Coelho, Sofia, Day, Suzanne, Desai, Monica, Dorman, Eleanor, Elliott, Tamara, Flight, Katie E, Fletcher, James, Galang, John, Gohil, Jagruti, Gupta, Aneta, Harlow, Chris, Hu, Kai, Kalyan, Mohini, Lagrue, Dominic, Liscano, Ely, Njenga, Cecilia, Polra, Krunal, Powlette, Derecia A, Randell, Paul, Rauchenberger, Mary, Redknap, Ianto, Ricamara, Maravic, Rogers, Paul, Sallah, Hadijatou, Samnuan, Karnyart, Schumacher, Michael, Shah, Zareena, Shaw, Rachel, Shaw, Thomas, Sivapatham, Stefan, Slater, Susie, Sorley, Kim, Storch, Regina, Tan, Elizabeth, Tan, Tricia, Thielemans, Lieze, Whitely, Sarah, Valentine, Charlotte, Varghese, Jeeva, Vikraman, Asha, Wilkins, Martin, Pollock, Katrina M., Cheeseman, Hannah M., Szubert, Alexander J., Libri, Vincenzo, Boffito, Marta, Owen, David, Bern, Henry, McFarlane, Leon R., O'Hara, Jessica, Lemm, Nana-Marie, McKay, Paul, Rampling, Tommy, Yim, Yee Ting N., Milinkovic, Ana, Kingsley, Cherry, Cole, Tom, Fagerbrink, Susanne, Aban, Marites, Tanaka, Maniola, Mehdipour, Savviz, Robbins, Alexander, Budd, William, Faust, Saul, Hassanin, Hana, Cosgrove, Catherine A., Winston, Alan, Fidler, Sarah, Dunn, David, McCormack, Sheena, and Shattock, Robin J.

Published
2022
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4. Cohort Profile: The Stroke in Sierra Leone (SISLE) Register

Author

Youkee, Daniel, primary, Marshall, Iain J, additional, Fox-Rushby, Julia, additional, Lisk, Durodami R, additional, O’Hara, Jessica, additional, Wang, Yanzhong, additional, Rudd, Anthony, additional, Wolfe, Charles D A, additional, Deen, Gibrilla F, additional, and Sackley, Catherine, additional

Published
2023
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5. Stroke in Sierra Leone: Case fatality rate and functional outcome after stroke in Freetown

Author

Youkee, Daniel, Deen, Gibrilla, Baldeh, Mamadu, Conteh, Zainab Fatmata, Fox-Rushby, Julia, Gbessay, Musa, Johnson, Jotham, Langhorne, Peter, Leather, Andrew, Lisk, Durodamil Radcliffe, Marshall, Iain, O'Hara, Jessica, Pessima, Sahr, Rudd, Anthony, Soley-Bori, Marina, Thompson, Melvina, Wafa, Hatem, Wang, Yanzhong, Watkins, Caroline Leigh, Williams, Christine, Wolfe, Charles, Sackley, Catherine, Youkee, Daniel, Deen, Gibrilla, Baldeh, Mamadu, Conteh, Zainab Fatmata, Fox-Rushby, Julia, Gbessay, Musa, Johnson, Jotham, Langhorne, Peter, Leather, Andrew, Lisk, Durodamil Radcliffe, Marshall, Iain, O'Hara, Jessica, Pessima, Sahr, Rudd, Anthony, Soley-Bori, Marina, Thompson, Melvina, Wafa, Hatem, Wang, Yanzhong, Watkins, Caroline Leigh, Williams, Christine, Wolfe, Charles, and Sackley, Catherine

Abstract

Background: There is limited information on long term outcomes after stroke in Sub-Saharan Africa (SSA). Current estimates of case fatality rate (CFR) in SSA are based on small sample sizes with varying study design and report high heterogeneity. Aims: We report CFR and functional outcomes from a large, prospective, longitudinal cohort of stroke patients in Sierra Leone and describe factors associated with mortality and functional outcome. Methods: A prospective longitudinal stroke register was established at both adult tertiary government hospitals in Freetown, Sierra Leone. It recruited all patients ≥18 years with stroke, using the World Health Organization definition, from May 2019 until October 2021. To reduce selection bias onto the register all investigations were paid by the funder and outreach conducted to raise awareness of the study. Sociodemographic data, National Institute of Health Stroke Scale (NIHSS) and Barthel Index (BI) was collected on all patients on admission, at seven days, 90 days, one year and two years post stroke. Cox proportional-hazards models were constructed to identify factors associated with all-cause mortality. A binomial logistic regression model reports odds ratio (OR) for functional independence at one year. Results: 986 patients with stroke were included, of which 847 (85.9%) received neuroimaging. Follow up rate was 81.5% at one year, missing item data was <1% for most variables. Stroke cases were equally split by sex and mean age was 58.9 (SD: 14.0) years. 625 (63%) were ischaemic, 206 (21%) primary intracerebral haemorrhage, 25 (3%) subarachnoid haemorrhage and 130 (13%) were of undetermined stroke type. Median NIHSS was 16 (9-24). CFR at 30 days, 90 days, 1 year and 2 years was 37.1%, 44.4%, 49.7% and 53.2% respectively. Factors associated with increased fatality were male sex HR:1.28 (1.05-1.56), previous stroke HR:1.34 (1.04-1.71), atrial fibrillation HR:1.58(1.06-2.34), subarachnoid haemorrhage HR:2.31 (1.40-3.81), unde

Published
2023

7. sj-docx-1-wso-10.1177_17474930231164892 – Supplemental material for Stroke in Sierra Leone: Case fatality rate and functional outcome after stroke in Freetown

Author

Youkee, Daniel, Deen, Gibrilla F, Baldeh, Mamadu, Conteh, Zainab F, Fox-Rushby, Julia, Gbessay, Musa, Johnson, Jotham, Langhorne, Peter, Leather, Andrew JM, Lisk, Durodami R, Marshall, Iain J, O’Hara, Jessica, Pessima, Sahr, Rudd, Anthony, Soley-Bori, Marina, Thompson, Melvina, Wafa, Hatem, Wang, Yanzhong, Watkins, Caroline L, Williams, Christine E, Wolfe, Charles DA, and Sackley, Catherine M

Subjects
FOS: Clinical medicine, Cardiology, Medicine, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, sj-docx-1-wso-10.1177_17474930231164892 for Stroke in Sierra Leone: Case fatality rate and functional outcome after stroke in Freetown by Daniel Youkee, Gibrilla F Deen, Mamadu Baldeh, Zainab F Conteh, Julia Fox-Rushby, Musa Gbessay, Jotham Johnson, Peter Langhorne, Andrew JM Leather, Durodami R Lisk, Iain J Marshall, Jessica O’Hara, Sahr Pessima, Anthony Rudd, Marina Soley-Bori, Melvina Thompson, Hatem Wafa, Yanzhong Wang, Caroline L Watkins, Christine E Williams, Charles DA Wolfe and Catherine M Sackley in International Journal of Stroke

Published
2023
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8. Stroke in Sierra Leone: Case fatality rate and functional outcome after stroke in Freetown

Author

Youkee, Daniel, primary, Deen, Gibrilla F, additional, Baldeh, Mamadu, additional, Conteh, Zainab F, additional, Fox-Rushby, Julia, additional, Gbessay, Musa, additional, Johnson, Jotham, additional, Langhorne, Peter, additional, Leather, Andrew JM, additional, Lisk, Durodami R, additional, Marshall, Iain J, additional, O’Hara, Jessica, additional, Pessima, Sahr, additional, Rudd, Anthony, additional, Soley-Bori, Marina, additional, Thompson, Melvina, additional, Wafa, Hatem, additional, Wang, Yanzhong, additional, Watkins, Caroline L, additional, Williams, Christine E, additional, Wolfe, Charles DA, additional, and Sackley, Catherine M, additional

Published
2023
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9. Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines

Author

Elliott, Tamara, primary, Cheeseman, Hannah M., additional, Evans, Abbey B., additional, Day, Suzanne, additional, McFarlane, Leon R., additional, O’Hara, Jessica, additional, Kalyan, Mohini, additional, Amini, Fahimah, additional, Cole, Tom, additional, Winston, Alan, additional, Fidler, Sarah, additional, Pollock, Katrina M., additional, Harker, James A., additional, and Shattock, Robin J., additional

Published
2022
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10. Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial

Author

Pollock, Katrina M., primary, Cheeseman, Hannah M., additional, Szubert, Alexander J., additional, Libri, Vincenzo, additional, Boffito, Marta, additional, Owen, David, additional, Bern, Henry, additional, McFarlane, Leon R., additional, O'Hara, Jessica, additional, Lemm, Nana-Marie, additional, McKay, Paul, additional, Rampling, Tommy, additional, Yim, Yee Ting N., additional, Milinkovic, Ana, additional, Kingsley, Cherry, additional, Cole, Tom, additional, Fagerbrink, Susanne, additional, Aban, Marites, additional, Tanaka, Maniola, additional, Mehdipour, Savviz, additional, Robbins, Alexander, additional, Budd, William, additional, Faust, Saul, additional, Hassanin, Hana, additional, Cosgrove, Catherine A., additional, Winston, Alan, additional, Fidler, Sarah, additional, Dunn, David, additional, McCormack, Sheena, additional, Shattock, Robin J., additional, Adams, Kirsty, additional, Amini, Fahimah, additional, Atako, Nafisah B, additional, Bakri, Amalina, additional, Barclay, Wendy, additional, Brodnicki, Elizabeth, additional, Brown, Jonathan C, additional, Byrne, Ruth, additional, Chilvers, Rowena, additional, Coelho, Sofia, additional, Day, Suzanne, additional, Desai, Monica, additional, Dorman, Eleanor, additional, Elliott, Tamara, additional, Flight, Katie E, additional, Fletcher, James, additional, Galang, John, additional, Gohil, Jagruti, additional, Gupta, Aneta, additional, Harlow, Chris, additional, Hu, Kai, additional, Kalyan, Mohini, additional, Lagrue, Dominic, additional, Liscano, Ely, additional, Njenga, Cecilia, additional, Polra, Krunal, additional, Powlette, Derecia A, additional, Randell, Paul, additional, Rauchenberger, Mary, additional, Redknap, Ianto, additional, Ricamara, Maravic, additional, Rogers, Paul, additional, Sallah, Hadijatou, additional, Samnuan, Karnyart, additional, Schumacher, Michael, additional, Shah, Zareena, additional, Shaw, Rachel, additional, Shaw, Thomas, additional, Sivapatham, Stefan, additional, Slater, Susie, additional, Sorley, Kim, additional, Storch, Regina, additional, Tan, Elizabeth, additional, Tan, Tricia, additional, Thielemans, Lieze, additional, Whitely, Sarah, additional, Valentine, Charlotte, additional, Varghese, Jeeva, additional, Vikraman, Asha, additional, and Wilkins, Martin, additional

Published
2022
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11. COVAC1 Phase 2a Expanded Safety and Immunogenicity Study of a Self-Amplifying RNA Vaccine Against SARS-CoV-2

Author

Szubert, Alexander J., primary, Pollock, Katrina M., additional, Cheeseman, Hannah M., additional, Alagaratnam, Jasmini, additional, Bern, Henry, additional, Bird, Olivia, additional, Boffito, Marta, additional, Byrne, Ruth, additional, Cole, Tom, additional, Cosgrove, Catherine A., additional, Faust, Saul N., additional, Fidler, Sarah, additional, Galiza, Eva, additional, Hassanin, Hana, additional, Kalyan, Mohini, additional, Libri, Vincenzo, additional, McFarlane, Leon R., additional, Milinkovic, Ana, additional, O’Hara, Jessica, additional, Owen, David R., additional, Owens, Daniel, additional, Pacurar, Mihaela, additional, Rampling, Tommy, additional, Skene, Simon S., additional, Winston, Alan, additional, Woolley, James, additional, Yim, Yee Ting N., additional, Dunn, David T., additional, McCormack, Sheena, additional, and Shattock, Robin John, additional

Published
2022
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13. A Prospective Stroke Register in Sierra Leone: Demographics, Stroke Type, Stroke Care and Hospital Outcomes

Author

Youkee, Daniel, primary, Deen, Gibrilla, additional, Barrett, Edward, additional, Fox-Rushby, Julia, additional, Johnson, Israel, additional, Langhorne, Peter, additional, Leather, Andrew, additional, Marshall, Iain J., additional, O'Hara, Jessica, additional, Rudd, Anthony, additional, Sama, Albert, additional, Scott, Christella, additional, Thompson, Melvina, additional, Wafa, Hatem, additional, Wall, Jurate, additional, Wang, Yanzhong, additional, Watkins, Caroline, additional, Wolfe, Charles, additional, Lisk, Durodami Radcliffe, additional, and Sackley, Catherine Mary, additional

Published
2021
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14. Impact of Inhibition of the TCA cycle on ATP and NADH levels in Escherichia coli during Bacterial Replication

Author

Suriaprakash, Aiswarya, O'Hara, Jessica, Suriaprakash, Aiswarya, Mercado, Briana, De La Cruz, Raina, Suriaprakash, Aiswarya, O'Hara, Jessica, Suriaprakash, Aiswarya, Mercado, Briana, and De La Cruz, Raina

Abstract

Bacteriophage are bacteria-eating viruses that utilize the host cell’s metabolic pathways for components for phage replication. The tricarboxylic acid (TCA) cycle, an important metabolic pathway within cellular respiration, uses oxygen to break down organic molecules to make adenosine triphosphate (ATP) for energy. In E. coli, the fumarase A gene codes for the enzyme fumarase, which catalyzes fumarate to (S)-malate and NAD+ in the TCA Cycle, used to create NADH, pyruvate, high-energy electron carriers, and ATP. The icd gene encodes the enzyme isocitrate dehydrogenase which is also used in the TCA cycle to make ATP. In our previous research, we discovered that the removal of the fumA and icd genes resulted in a delay in T4 and/or T4r bacteriophage replication. Currently, we are aiming to quantify ATP and NADH levels before and after cell lysis to further understand the impacts of each knockout on cellular metabolism and the resulting impact on T4 replication. This research is made to further understand ways to treat bacterial diseases in the face of antibiotic resistance, specifically phage therapy.

Published
2021

15. Characterizing a Chimera: Comparative Analysis of Pal Endolysin and its Homologs

Author

Griffin, Ryleigh, O'Hara, Jessica, Nelson, Daniel, Griffin, Ryleigh, Lee, Harrison, Griffin, Ryleigh, O'Hara, Jessica, Nelson, Daniel, Griffin, Ryleigh, and Lee, Harrison

Abstract

Once a virus infects a cell and produces more virus particles (virions), it must find a way to release those virions so they can infect more cells. Bacteriophage, or viruses that infect bacteria, accomplish this goal by producing endolysins, proteins that cause bacterial cells to lyse by breaking down their cell walls. Many endolysins have a modular structure consisting of an enzymatically active domain (EAD), which catalytically breaks bonds in peptidoglycan, the main component of bacterial cell walls, and a cell wall binding domain (CBD), which attaches the endolysin to the cell wall and determines host specificity. By combining EADs and CBDs from different endolysins, researchers can produce new “chimeric” endolysins in order to kill disease-causing bacteria in a targeted fashion, which can be more effective than the original enzymes. Chimeric endolysins can also form naturally. Bacteriophage Dp-1, which infects Streptococcus pneumoniae bacteria, produces a chimeric endolysin called Pal. Pal’s CBD has the ability to bind to choline and is very similar to a portion of the LytA enzyme produced by S. pneumoniae. Pal’s EAD breaks down amide bonds in peptidoglycan and is very similar to a portion of the endolysin produced by a Bacteriophage BK5-T, which infects Lactococcus lactis bacteria. In our research, we used bioinformatics techniques to find other proteins that share homology with Pal and to investigate the evolutionary relationships between these proteins. We hope that a better understanding of this natural chimeric endolysin could be useful to researchers attempting to engineer new ones.

Published
2021

16. Identification of Clostridium Phage Endolysins with Novel Multimeric Genetic Sequences

Author

Bokil, Eesha, Nelson, Daniel, O'Hara, Jessica, Bokil, Eesha, Baker, Charley, Bokil, Eesha, Nelson, Daniel, O'Hara, Jessica, Bokil, Eesha, and Baker, Charley

Abstract

The endolysin CD27L is produced by the Clostridium phage phiCD27. This phage targets the bacteria and uses the endolysin’s enzymatic properties to lyse cells from within and release new replicated phages. Past studies have characterized the two domains of CD27L’s genetic sequence, the enzymatically active domain (EAD) at the N-terminus and the cell wall binding domain (CBD) at the C-terminus connected by a linker sequence. The gene sequence order is EAD-linker-CBD. A unique aspect of CD27L is its ability to form a multimeric enzymatic structure from these two domains where one EAD and multiple CBDs are present in one structure. This multimeric endolysin is formed from one gene, so translation of the one sequence uses two ribosome binding sites and two start codons. One ribosome binding site and start codon is before the EAD and the other in the linker sequence before the CBD. Our goal is to analyze the sequences of other Clostridium phage endolysins to find multimeric endolysins similar to CD27L. We are specifically looking for multiple ribosome binding sites with start codons or alternate start codons downstream in close proximity on one gene sequence.

Published
2021

17. SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study

Author

Moshe, Maya, primary, Daunt, Anna, additional, Flower, Barnaby, additional, Simmons, Bryony, additional, Brown, Jonathan C, additional, Frise, Rebecca, additional, Penn, Rebecca, additional, Kugathasan, Ruthiran, additional, Petersen, Claire, additional, Stockmann, Helen, additional, Ashby, Deborah, additional, Riley, Steven, additional, Atchison, Christina, additional, Taylor, Graham P, additional, Satkunarajah, Sutha, additional, Naar, Lenny, additional, Klaber, Robert, additional, Badhan, Anjna, additional, Rosadas, Carolina, additional, Marchesin, Federica, additional, Fernandez, Natalia, additional, Sureda-Vives, Macià, additional, Cheeseman, Hannah, additional, O’Hara, Jessica, additional, Shattock, Robin, additional, Fontana, Gianluca, additional, Pallett, Scott J C, additional, Rayment, Michael, additional, Jones, Rachael, additional, Moore, Luke S P, additional, Ashrafian, Hutan, additional, Cherapanov, Peter, additional, Tedder, Richard, additional, McClure, Myra, additional, Ward, Helen, additional, Darzi, Ara, additional, Elliott, Paul, additional, Cooke, Graham S, additional, and Barclay, Wendy S, additional

Published
2021
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18. Safety and Immunogenicity of a Self-Amplifying RNA Vaccine Against COVID-19: COVAC1, a Phase I, Dose-Ranging Trial

Author

Pollock, Katrina M., primary, Cheeseman, Hannah M., additional, Szubert, Alexander J., additional, Libri, Vincenzo, additional, Boffito, Marta, additional, Owen, David, additional, Bern, Henry, additional, O’Hara, Jessica, additional, McFarlane, Leon R., additional, Lemm, Nana-Marie, additional, McKay, Paul F., additional, Rampling, Tommy, additional, Yim, Yee Ting N., additional, Milinkovic, Ana, additional, Kingsley, Cherry, additional, Cole, Tom, additional, Fagerbrink, Susanne, additional, Aban, Marites, additional, Tanaka, Maniola, additional, Mehdipour, Savviz, additional, Robbins, Alexander, additional, Budd, William, additional, Faust, Saul N., additional, Hassanin, Hana, additional, Cosgrove, Catherine A., additional, Winston, Alan, additional, Fidler, Sarah, additional, Dunn, David T., additional, McCormack, Sheena, additional, and Shattock, Robin John, additional

Published
2021
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19. Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey

Author

Flower, Barnaby, primary, Brown, Jonathan C, additional, Simmons, Bryony, additional, Moshe, Maya, additional, Frise, Rebecca, additional, Penn, Rebecca, additional, Kugathasan, Ruthiran, additional, Petersen, Claire, additional, Daunt, Anna, additional, Ashby, Deborah, additional, Riley, Steven, additional, Atchison, Christina Joanne, additional, Taylor, Graham P, additional, Satkunarajah, Sutha, additional, Naar, Lenny, additional, Klaber, Robert, additional, Badhan, Anjna, additional, Rosadas, Carolina, additional, Khan, Maryam, additional, Fernandez, Natalia, additional, Sureda-Vives, Macià, additional, Cheeseman, Hannah M, additional, O'Hara, Jessica, additional, Fontana, Gianluca, additional, Pallett, Scott J C, additional, Rayment, Michael, additional, Jones, Rachael, additional, Moore, Luke S P, additional, McClure, Myra O, additional, Cherepanov, Peter, additional, Tedder, Richard, additional, Ashrafian, Hutan, additional, Shattock, Robin, additional, Ward, Helen, additional, Darzi, Ara, additional, Elliot, Paul, additional, Barclay, Wendy S, additional, and Cooke, Graham S, additional

Published
2020
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20. Co-production of NDM-1 and OXA-232 by Klebsiella pneumoniae

Author

Doi, Yohei, O'Hara, Jessica A., Lando, James F., Querry, Ashley M., Townsend, Bethany M., Pasculle, Anthony W., and Muto, Carlene A.

Subjects
Identification and classification, Physiological aspects, Case studies, Microbial enzymes -- Physiological aspects, Klebsiella -- Identification and classification -- Physiological aspects -- Case studies, Escherichia coli -- Identification and classification -- Physiological aspects -- Case studies
Abstract

To the Editor: New Delhi metallo-[beta]-lactamase 1 (NDM-1) and OXA-48-group [beta]-lactamase have been increasingly reported as carbapenemases responsible for carbapenem resistance in Enterobacteriaceae worldwide (1). However, in the United States, [...]

Published
2014

21. Investigating Arginine Biosynthesis in Viral Replication

Author

Lee, Harrison, O'Hara, Jessica, Lee, Harrison, Griffin, Ryleigh, Stecklein, Sabrina, Chaudry, Daniel, Lee, Harrison, O'Hara, Jessica, Lee, Harrison, Griffin, Ryleigh, Stecklein, Sabrina, and Chaudry, Daniel

Published
2020

22. Implications of the TCA Cycle on Escherichia coli Growth and Phage Replication

Author

Suriaprakash, Aiswarya, O'Hara, Jessica, Suriaprakash, Aiswarya, Bokil, Eesha, Koudouovoh, Carlos, Chuck, Marissa, Suriaprakash, Aiswarya, O'Hara, Jessica, Suriaprakash, Aiswarya, Bokil, Eesha, Koudouovoh, Carlos, and Chuck, Marissa

Abstract

ATP provides energy for the cellular processes in E. coli. The E. coli icd gene encodes the enzyme isocitrate dehydrogenase which is used in the tricarboxylic acid (TCA) cycle to make ATP. We hypothesize that T4 phage is dependent on ATP production in the host cell in order to successfully replicate. Our research aims to find if an E. coli bacteria strain lacking the icd gene will show decreased T4 phage replication because of its decreased ATP production compared to E. coli bacteria strains that possess the icd gene with normal ATP production. Decreased ATP production in the E. coli host will result in a decrease in bacterial growth rate and T4 phage replication. Plaque assays, growth curves, and lysis curves were used to monitor bacterial growth and phage replication. Host cells lacking the icd gene had decreased bacterial growth. T4 phage replication is slower in the host cells lacking the icd gene. It is the hope that these results and future research will contribute to phage therapy, a promising development in treating bacterial diseases.

Published
2020

33. Aerosolization of Acinetobacter baumannii in a Trauma ICU*

Author

Munoz-Price, L. Silvia, primary, Fajardo-Aquino, Yovanit, additional, Arheart, Kristopher L., additional, Cleary, Timothy, additional, DePascale, Dennise, additional, Pizano, Louis, additional, Namias, Nicholas, additional, Rivera, Jesabel I., additional, O’Hara, Jessica A., additional, and Doi, Yohei, additional

Published
2013
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37. Targeting NAD+ Metabolism in the Human Malaria Parasite Plasmodium falciparum.

Author

O'Hara, Jessica K., Kerwin, Lewis J., Cobbold, Simon A., Tai, Jonathan, Bedell, Thomas A., Reider, Paul J., and Llinás, Manuel

Subjects
*NAD (Coenzyme), *PLASMODIUM, *MICROBIAL metabolism, *ERYTHROCYTE disorders, *ENZYME inhibitors, *TARGETED drug delivery
Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+de novo and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD+ pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of these enzymes, the P. falciparum nicotinate mononucleotide adenylyltransferase (PfNMNAT), is essential for NAD+ metabolism and is highly diverged from the human homolog, but genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic activity of PfNMNAT in vitro and demonstrate its ability to genetically complement the closely related Escherichia coli NMNAT. Due to the similarity of PfNMNAT to the bacterial enzyme, we tested a panel of previously identified bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives, which demonstrate a range of potency against live parasite culture. These results highlight the importance of the parasite NAD+ metabolic pathway and provide both novel therapeutic targets and promising lead antimalarial compounds. [ABSTRACT FROM AUTHOR]

Published
2014
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38. Targeting NAD+ Metabolism in the Human Malaria Parasite Plasmodium falciparum.

Author

O'Hara, Jessica K., Kerwin, Lewis J., Cobbold, Simon A., Tai, Jonathan, Bedell, Thomas A., Reider, Paul J., and Llinás, Manuel

Subjects
NAD (Coenzyme), PLASMODIUM, MICROBIAL metabolism, ERYTHROCYTE disorders, ENZYME inhibitors, TARGETED drug delivery
Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+de novo and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD+ pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of these enzymes, the P. falciparum nicotinate mononucleotide adenylyltransferase (PfNMNAT), is essential for NAD+ metabolism and is highly diverged from the human homolog, but genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic activity of PfNMNAT in vitro and demonstrate its ability to genetically complement the closely related Escherichia coli NMNAT. Due to the similarity of PfNMNAT to the bacterial enzyme, we tested a panel of previously identified bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives, which demonstrate a range of potency against live parasite culture. These results highlight the importance of the parasite NAD+ metabolic pathway and provide both novel therapeutic targets and promising lead antimalarial compounds. [ABSTRACT FROM AUTHOR]

Published
2014
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39. U.S. Department of Health and Human Services Oral Health Strategic Framework, 2014–2017

Author

Adesanya, Margo R., Bailey, William, Belcher, Donald C., Beltran, Marco, Branch, Tracy, Brand, Marcia K., Craft, Edwin M., Donahue, Agnes H., Dye, Bruce A., Thornton-Evans, Gina, Garcia, Isabel, Hyman, Frederick, Joskow, Renée, Lester, Arlene M., Makrides, Nicholas S., Manski, Richard J., Mehegan, Marian, Mouden, Lynn Douglas, Nelson, Danielle, Norris, Laurie, O'Hara, Jessica, Cherry-Peppers, Gail, Ricks, Timothy L., and Rollins, Rochelle

Published
2016
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40. Screening for Methicillin-Resistant Staphylococcus aureusColonization Using Sponges

Author

Lee, Chang-Seop, Montalmont, Bianca, O’Hara, Jessica A., Syed, Alveena, Chaussard, Charma, McGaha, Traci L., Pakstis, Diana L., Lee, Ju-Hyung, Shutt, Kathleen A., and Doi, Yohei

Abstract

OBJECTIVENasal swab culture is the standard method for identifying methicillin-resistant Staphylococcus aureus(MRSA) carriers. However, this method is known to miss a substantial portion of those carrying MRSA elsewhere. We hypothesized that the additional use of a sponge to collect skin culture samples would significantly improve the sensitivity of MRSA detection.DESIGNHospitalized patients with recent MRSA infection were enrolled and underwent MRSA screening of the forehead, nostrils, pharynx, axilla, and groin with separate swabs and the forehead, axilla, and groin with separate sponges. Staphylococcal cassette chromosome mec(SCCmec) typing was conducted by polymerase chain reaction (PCR).PATIENTSA total of 105 MRSA patients were included in the study.RESULTSAt least 1 specimen from 56.2% of the patients grew MRSA. Among patients with at least 1 positive specimen, the detection sensitivities were 79.7% for the swabs and 64.4% for the sponges. Notably, 86.4% were detected by a combination of sponges and nasal swab, and 72.9% were detected by a combination of pharyngeal and nasal swabs, whereas only 50.9% were detected by nasal swab alone (P<0.0001 and P=0.0003, respectively). Most isolates had SCCmectype II (59.9%) and IV (35.7%). No correlation was observed between the SCCmectypes and collection sites.CONCLUSIONScreening using a sponge significantly improves MRSA detection when used in addition to screening with the standard nasal swab.Infect Control Hosp Epidemiol 2014;36(1): 28–33

Published
2015
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41. Molecular Features of Community-Associated Extended-Spectrum-β-Lactamase-Producing Escherichia coliStrains in the United States

Author

Hu, Fupin, O'Hara, Jessica A., Rivera, Jesabel I., and Doi, Yohei

Abstract

ABSTRACTWe characterized 30 community-associated extended-spectrum-β-lactamase-producing Escherichia coliisolates collected from five hospitals in the United States. Nineteen sequence types were identified. All sequence type 131 (ST131) isolates had the fimH30 allele. IncFII-FIA-FIB was the most common replicon type among the blaCTX-M-carrying plasmids, followed by IncFII-FIA and IncA/C. Restriction analysis of the IncFII-FIA-FIB and IncFII-FIA plasmids yielded related profiles for plasmids originating from different hospitals. The plasmids containing blaCTX-Mor blaSHVwere stably maintained after serial passages.

Published
2014
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42. Molecular Epidemiology of KPC-Producing Escherichia coli: Occurrence of ST131-fimH30Subclone Harboring pKpQIL-Like IncFIIk Plasmid

Author

O'Hara, Jessica A., Hu, Fupin, Ahn, Chulsoo, Nelson, Jeremy, Rivera, Jesabel I., Pasculle, Anthony W., and Doi, Yohei

Abstract

ABSTRACTOf 20 Klebsiella pneumoniaecarbapenemase (KPC)-producing Escherichia coliisolates identified at hospitals in western Pennsylvania, 60% belonged to the epidemic ST131-fimH30subclone. IncFIIk was the most common replicon type for the blaKPC-carrying plasmids (n= 8). All IncFIIk plasmids possessed a scaffold similar to that of pKpQIL, and seven of them were borne by ST131-fimH30isolates. IncN plasmids conferred resistance to trimethoprim-sulfamethoxazole, and IncA/C plasmids conferred resistance to gentamicin. Three blaKPC-carrying plasmids (IncA/C and IncN) possessed blaSHV-7/12and qnrA1or qnrS1.

Published
2014
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43. In VitroResponses of Acinetobacter baumanniito Two- and Three-Drug Combinations following Exposure to Colistin and Doripenem

Author

Oleksiuk, Louise M., Nguyen, M. Hong, Press, Ellen G., Updike, Cassaundra L., O'Hara, Jessica A., Doi, Yohei, Clancy, Cornelius J., and Shields, Ryan K.

Abstract

ABSTRACTWe compared in vitrokilling of colistin, doripenem, and sulbactam by time-kill methods against Acinetobacter baumanniiisolates collected from patients before and after colistin-doripenem treatment (initial and recurrent isolates, respectively). Colistin-doripenem bactericidal activity against recurrent isolates was attenuated (mean log10kill, −5.74 versus −2.88; P= 0.01) but was restored by adding sulbactam. Doripenem MICs rather than colistin MICs correlated with the activity of colistin-doripenem. Among colistin-resistant isolates, colistin-doripenem-sulbactam combinations achieved greater killing than colistin-doripenem alone (−5.65 versus −2.43; P= 0.04).

Published
2013
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44. Novel 16S rRNA Methyltransferase RmtH Produced by Klebsiella pneumoniaeAssociated with War-Related Trauma

Author

O'Hara, Jessica A., McGann, Patrick, Snesrud, Erik C., Clifford, Robert J., Waterman, Paige E., Lesho, Emil P., and Doi, Yohei

Abstract

ABSTRACTKlebsiella pneumoniaestrain MRSN2404 was isolated from the chronic wound of a soldier who had been wounded in Iraq in 2006. The strain displayed very high MICs of all aminoglycosides, including arbekacin. A gene encoding a novel 16S rRNA methyltransferase, now designated RmtH, was identified. RmtH had 64% identity with RmtB1 and RmtB2. rmtHwas bracketed by two copies of ISCR2, which may have played a role in its mobilization.

Published
2013
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45. Activities of Vancomycin-Containing Regimens against Colistin-Resistant Acinetobacter baumanniiClinical Strains

Author

O'Hara, Jessica A., Ambe, Lauretta A., Casella, Leila G., Townsend, Bethany M., Pelletier, Mark R., Ernst, Robert K., Shanks, Robert M. Q., and Doi, Yohei

Abstract

ABSTRACTTreatment of infections due to extensively drug-resistant (XDR) Acinetobacter baumanniioften involves the use of antimicrobial agents in combination. Various combinations of agents have been proposed, with colistin serving as the backbone in many of them. Recent data suggest that glycopeptides, in particular vancomycin, may have unique activity against laboratory-adapted and clinical strains of A. baumannii, alone and in combination with colistin. The aim of the present study was to test this approach against three unique colistin-resistant A. baumanniiclinical strains using combinations of vancomycin (VAN), colistin (COL), and doripenem (DOR). All three strains possessed the signature phosphoethanolamine modification of the lipid A moiety associated with colistin resistance and unique amino acid changes in the PmrAB two-component signal transduction system not observed in colistin-susceptible strains. In checkerboard assays, synergy (defined as a fractional inhibitory concentration index [FICI] of ≤0.5) was observed between COL and VAN for all three strains tested and between COL and DOR in two strains. In time-kill assays, the combinations of COL-DOR, COL-VAN, and COL-DOR-VAN resulted in complete killing of colistin-resistant A. baumanniiin 1, 2, and all 3 strains, respectively. In the Galleria mellonellamoth model of infection, the combinations of DOR-VAN and COL-DOR-VAN led to significantly increased survival of the larvae, compared with other combinations and monotherapy. These findings suggest that regimens containing vancomycin may confer therapeutic benefit for infection due to colistin-resistant A. baumannii.

Published
2013
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