Publications by authors named "Claire Dodd"

6 Publications

  • Page 1 of 1

Top-down proteomic identification of plasmid and host proteins produced by pathogenic Escherichia coli using MALDI-TOF-TOF tandem mass spectrometry.

PLoS One 2021 29;16(11):e0260650. Epub 2021 Nov 29.

Produce Safety & Microbiology, Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, California, United States of America.

Fourteen proteins produced by three pathogenic Escherichia coli strains were identified using antibiotic induction, MALDI-TOF-TOF tandem mass spectrometry (MS/MS) and top-down proteomic analysis using software developed in-house. Host proteins as well as plasmid proteins were identified. Mature, intact protein ions were fragmented by post-source decay (PSD), and prominent fragment ions resulted from the aspartic acid effect fragmentation mechanism wherein polypeptide backbone cleavage (PBC) occurs on the C-terminal side of aspartic acid (D), glutamic acid (E) and asparagine (N) residues. These highly specific MS/MS-PSD fragment ions were compared to b- and y-type fragment ions on the C-terminal side of D-, E- and N-residues of in silico protein sequences derived from whole genome sequencing. Nine proteins were found to be post-translationally modified with either removal of an N-terminal methionine or a signal peptide. The protein sequence truncation algorithm of our software correctly identified all full and truncated protein sequences. Truncated sequences were compared to those predicted by SignalP. Nearly complete concurrence was obtained except for one protein where SignalP mis-identified the cleavage site by one residue. Two proteins had intramolecular disulfide bonds that were inferred by the absence of PBC on the C-terminal side of a D-residue located within the disulfide loop. These results demonstrate the utility of MALDI-TOF-TOF for identification of full and truncated bacterial proteins.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260650PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629258PMC
January 2022

New concepts in understanding latent tuberculosis.

Curr Opin Infect Dis 2017 Jun;30(3):316-321

aDepartment of Microbiology bDepartment of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, USA.

Purpose Of Review: Mycobacterium tuberculosis (M.tb), the etiologic agent of tuberculosis, is a prominent global health threat because of the enormous reservoir of subclinical latent tuberculosis infection (LTBI). Current diagnostic approaches are limited in their ability to predict reactivation risk and LTBI is recalcitrant to antibiotic treatment. The present review summarizes recent advances in our ability to detect, treat and model LTBI as well as our understanding of bacterial physiology during latency.

Recent Findings: T-cell subsets and circulating proteins have been identified which could serve as biomarkers for LTBI or indicators of reactivation risk. In addition, experimental and in-silico models have enabled discoveries regarding bacterial physiology during latency and the host immune response following infection with latent M.tb.

Summary: Despite recent advances, much more research is needed to bolster our ability to detect, implement treatment and model LTBI. The present work is crucial for the eradication of this global problem.
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http://dx.doi.org/10.1097/QCO.0000000000000367DOI Listing
June 2017

Zinc Modulates Endotoxin-Induced Human Macrophage Inflammation through ZIP8 Induction and C/EBPβ Inhibition.

PLoS One 2017 5;12(1):e0169531. Epub 2017 Jan 5.

Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, United States of America.

Two vital functions of the innate immune system are to initiate inflammation and redistribute micronutrients in favor of the host. Zinc is an essential micronutrient used in host defense. The zinc importer ZIP8 is uniquely induced through stimulation of the NF-κB pathway by LPS in monocytes and functions to regulate inflammation in a zinc-dependent manner. Herein we determined the impact of zinc metabolism following LPS-induced inflammation in human macrophages. We observed that ZIP8 is constitutively expressed in resting macrophages and strikingly elevated following LPS exposure, a response that is unique compared to the 13 other known zinc import proteins. During LPS exposure, extracellular zinc concentrations within the physiological range markedly reduced IL-10 mRNA expression and protein release but increased mRNA expression of TNFα, IL-8, and IL-6. ZIP8 knockdown inhibited LPS-driven cellular accumulation of zinc and prevented zinc-dependent reduction of IL-10 release. Further, zinc supplementation reduced nuclear localization and activity of C/EBPβ, a transcription factor known to drive IL-10 expression. These studies demonstrate for the first time that zinc regulates LPS-mediated immune activation of human macrophages in a ZIP8-dependent manner, reducing IL-10. Based on these findings we predict that macrophage zinc metabolism is important in host defense against pathogens.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169531PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215883PMC
August 2017

CD36-Mediated Uptake of Surfactant Lipids by Human Macrophages Promotes Intracellular Growth of Mycobacterium tuberculosis.

J Immunol 2016 12 9;197(12):4727-4735. Epub 2016 Nov 9.

Department of Microbiology, The Ohio State University, Columbus, OH 43210; and

Mycobacterium tuberculosis imposes a large global health burden as the airborne agent of tuberculosis. Mycobacterium tuberculosis has been flourishing in human populations for millennia and is therefore highly adapted to the lung environment. Alveolar macrophages, a major host cell niche for M. tuberculosis, are not only phagocytose inhaled microbes and particulate matter but are also crucial in catabolizing lung surfactant, a lipid-protein complex that lines the alveolar spaces. Because macrophage host defense properties can be regulated by surfactant and M. tuberculosis can use host lipids as a carbon source during infection, we sought to determine the receptor(s) involved in surfactant lipid uptake by human macrophages and whether the presence of those lipids within macrophages prior to infection with M. tuberculosis enhances bacterial growth. We show that preformed scavenger receptor CD36 is redistributed to the cell membrane following exposure to surfactant lipids and surfactant protein A. Subsequently, surfactant lipids and/or surfactant protein A enhance CD36 transcript and protein levels. We show that CD36 participates in surfactant lipid uptake by human macrophages, as CD36 knockdown reduces uptake of dipalmitoylphosphatidylcholine, the most prevalent surfactant lipid species. Finally, exposing human macrophages to surfactant lipids prior to infection augments M. tuberculosis growth in a CD36-dependent manner. Thus, we provide evidence that CD36 mediates surfactant lipid uptake by human macrophages and that M. tuberculosis exploits this function for growth.
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http://dx.doi.org/10.4049/jimmunol.1600856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137803PMC
December 2016

Macrophage immunoregulatory pathways in tuberculosis.

Semin Immunol 2014 Dec 30;26(6):471-85. Epub 2014 Oct 30.

Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA; Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Macrophages, the major host cells harboring Mycobacterium tuberculosis (M.tb), are a heterogeneous cell type depending on their tissue of origin and host they are derived from. Significant discord in macrophage responses to M.tb exists due to differences in M.tb strains and the various types of macrophages used to study tuberculosis (TB). This review will summarize current concepts regarding macrophage responses to M.tb infection, while pointing out relevant differences in experimental outcomes due to the use of divergent model systems. A brief description of the lung environment is included since there is increasing evidence that the alveolar macrophage (AM) has immunoregulatory properties that can delay optimal protective host immune responses. In this context, this review focuses on selected macrophage immunoregulatory pattern recognition receptors (PRRs), cytokines, negative regulators of inflammation, lipid mediators and microRNAs (miRNAs).
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http://dx.doi.org/10.1016/j.smim.2014.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314327PMC
December 2014

Clinco-epidemiologic study of cutaneous leishmaniasis in Bikaner, Rajasthan, India.

Am J Trop Med Hyg 2013 Jul 28;89(1):111-5. Epub 2013 May 28.

Department of Dermatology, Sandar Patel Medical College, Bikaner, Rajasthan, India.

Cutaneous leishmaniasis is endemic to the Thar Desert of Rajasthan, Bikaner, India. The present study describes clinico-epidemiologcial data of all cases of cutaneous leishmaniasis CL in this region during 2001-2011. A total of 1,379 patients with 2,730 lesions were reported during the study period. Ages of patients ranged from 3 months to 86 years, and there was a predominance of infections in males. Most patients were from urban areas and lower middle socioeconomic groups. Lesions were dry, ulcerated nodules or plaques of different sizes commonly over face and upper limb. Skin smears were positive for parasites in 958 (69.5%) patients, and the remaining 45.8% (193 of 421) patients were positive by skin biopsy. Histopathologic analysis of the skin showed mixed granulomas consisting of macrophages, lymphocytes, epitheloid, and plasma cells. Species identification was conducted for 45 randomly selected patients by polymerase chain reaction, the infective species was Leishmania tropica. Most patients were treated with intra-lesional injections of sodium stibogluconate.
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http://dx.doi.org/10.4269/ajtmh.12-0558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748465PMC
July 2013
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