Dominique Carter - Academia.edu (original) (raw)
Papers by Dominique Carter
Journal of Bacteriology
Mycobacterium tuberculosis is a global pathogen of significant medical importance. A key aspect o... more Mycobacterium tuberculosis is a global pathogen of significant medical importance. A key aspect of its life cycle is the ability to enter into an altered physiological state of nonreplicating persistence during latency and resist elimination by the host immune system. One mechanism by which M. tuberculosis facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are quasi-organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins. We previously reported that PspA (phage shock protein A) associates with LDs produced in Mycobacterium. In particular, the loss or overproduction of PspA alters LD homeostasis in Mycobacterium smegmatis and attenuates the survival of M. tuberculosis during nonreplicating persistence. Here, M. tuberculosis PspA (PspAMtb) and a ΔpspA M. smegmatis mutant were used as model systems to investigate the mechanism by which PspA associates with ...
Journal of bacteriology, Jan 14, 2018
is a global pathogen of significant medical importance. A key aspect of its lifecycle is the abil... more is a global pathogen of significant medical importance. A key aspect of its lifecycle is the ability to enter into an altered physiological state of non-replicating persistence during latency and resist elimination by the host immune system. One mechanism by which facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are semi-quasi organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins. We previously reported that PspA (phage shock protein A) associates with LDs produced in In particular, loss or overproduction of PspA alters LD homeostasis in , and attenuates survival of during non-replicating persistence. Here, PspA (PspA) and a Δ mutant were used as model systems to investigate the mechanism by which PspA associates with LDs, and determine if other proteins associate with LDs using a mechanism similar to PspA. Through this work, we established that the ...
Molecular & cellular proteomics : MCP, 2017
Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm... more Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. Although this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase. F10 is essential for virion morphogenesis, beginning with the poorly understood process of diversion of membranes from the ER for the purpose of virion membrane biogenesis. To better understand the function of F10, we generated a cell line that carries a single, inducible F10 transgene. Using uninduced and induced cells, we performed stable isotope labeling of amino acids in cell culture (SILAC) coupled with phosphopeptide analysis to identify cellular targets of F10-mediated phosphorylation. We identified 27 proteins that sh...
PROTEOMICS, 2015
Human cytomegalovirus (HCMV) is a herpesvirus that is ubiquitously distributed world-wide and cau... more Human cytomegalovirus (HCMV) is a herpesvirus that is ubiquitously distributed world-wide and causes life-threating disease upon immunosuppression. HCMV expresses numerous proteins that function to establish an intracellular environment that supports viral replication. Like most DNA viruses, HCMV manipulates processes within the nucleus. We have quantified changes in the host cell nuclear proteome at 24 hpi following infection with a clinical viral isolate. We have combined SILAC with multiple stages of fractionation to define changes. Tryptic peptides were analyzed by RP-HPLC combined with LC-MS/MS on an LTQ Orbitrap Velos mass spectrometer. Data from three biological replicates were processed with MaxQuant. A total of 1281 cellular proteins were quantified and 77 were found to be significantly differentially expressed. In addition, we observed 36 viral proteins associated with the nucleus. Diverse biological processes were significantly altered including increased aspects of cell cycling, mRNA metabolism, and nucleocytoplasmic transport while decreased immune responses. We validated changes for several proteins including a subset of classical nuclear transport proteins. In addition, we demonstrated that disruption of these import factors is inhibitory to HCMV replication. Overall, we have identified HCMV-induced changes in the nuclear proteome and uncovered several processes that are important for infection. This article is protected by copyright. All rights reserved.
Journal of Bacteriology
Mycobacterium tuberculosis is a global pathogen of significant medical importance. A key aspect o... more Mycobacterium tuberculosis is a global pathogen of significant medical importance. A key aspect of its life cycle is the ability to enter into an altered physiological state of nonreplicating persistence during latency and resist elimination by the host immune system. One mechanism by which M. tuberculosis facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are quasi-organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins. We previously reported that PspA (phage shock protein A) associates with LDs produced in Mycobacterium. In particular, the loss or overproduction of PspA alters LD homeostasis in Mycobacterium smegmatis and attenuates the survival of M. tuberculosis during nonreplicating persistence. Here, M. tuberculosis PspA (PspAMtb) and a ΔpspA M. smegmatis mutant were used as model systems to investigate the mechanism by which PspA associates with ...
Journal of bacteriology, Jan 14, 2018
is a global pathogen of significant medical importance. A key aspect of its lifecycle is the abil... more is a global pathogen of significant medical importance. A key aspect of its lifecycle is the ability to enter into an altered physiological state of non-replicating persistence during latency and resist elimination by the host immune system. One mechanism by which facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are semi-quasi organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins. We previously reported that PspA (phage shock protein A) associates with LDs produced in In particular, loss or overproduction of PspA alters LD homeostasis in , and attenuates survival of during non-replicating persistence. Here, PspA (PspA) and a Δ mutant were used as model systems to investigate the mechanism by which PspA associates with LDs, and determine if other proteins associate with LDs using a mechanism similar to PspA. Through this work, we established that the ...
Molecular & cellular proteomics : MCP, 2017
Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm... more Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. Although this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase. F10 is essential for virion morphogenesis, beginning with the poorly understood process of diversion of membranes from the ER for the purpose of virion membrane biogenesis. To better understand the function of F10, we generated a cell line that carries a single, inducible F10 transgene. Using uninduced and induced cells, we performed stable isotope labeling of amino acids in cell culture (SILAC) coupled with phosphopeptide analysis to identify cellular targets of F10-mediated phosphorylation. We identified 27 proteins that sh...
PROTEOMICS, 2015
Human cytomegalovirus (HCMV) is a herpesvirus that is ubiquitously distributed world-wide and cau... more Human cytomegalovirus (HCMV) is a herpesvirus that is ubiquitously distributed world-wide and causes life-threating disease upon immunosuppression. HCMV expresses numerous proteins that function to establish an intracellular environment that supports viral replication. Like most DNA viruses, HCMV manipulates processes within the nucleus. We have quantified changes in the host cell nuclear proteome at 24 hpi following infection with a clinical viral isolate. We have combined SILAC with multiple stages of fractionation to define changes. Tryptic peptides were analyzed by RP-HPLC combined with LC-MS/MS on an LTQ Orbitrap Velos mass spectrometer. Data from three biological replicates were processed with MaxQuant. A total of 1281 cellular proteins were quantified and 77 were found to be significantly differentially expressed. In addition, we observed 36 viral proteins associated with the nucleus. Diverse biological processes were significantly altered including increased aspects of cell cycling, mRNA metabolism, and nucleocytoplasmic transport while decreased immune responses. We validated changes for several proteins including a subset of classical nuclear transport proteins. In addition, we demonstrated that disruption of these import factors is inhibitory to HCMV replication. Overall, we have identified HCMV-induced changes in the nuclear proteome and uncovered several processes that are important for infection. This article is protected by copyright. All rights reserved.