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Illuminating Targets of Bacterial Secretion

Roger D. Pechous, William E. Goldman, Deborah A. Hogan
2015 PLoS Pathogens  
The ability to secrete proteins is important to the pathogenesis of many bacteria. For gram-negative bacteria, the secretion system must deliver cargo through both an inner and outer membrane to reach a potential target. To date, there are six known gram-negative bacterial secretion systems, designated types I-VI secretion. For many highly pathogenic bacteria including Yersinia pestis and Salmonella typhimurium, secretion of protein effectors directly into target host cells is essential for
more » ... lence. Proteins secreted via the type III, IV, and VI pathways result in direct transfer of proteins across the host membrane and into the cytosol, and these systems will be the focus of the technology highlighted in this article. Although the function of effector proteins secreted by these systems varies among different pathogens, common virulence mechanisms are evident. One common function of many secreted virulence factors is the targeting of host cytoskeletal function in order to promote uptake or inhibit phagocytosis. Another is modulating host cell cytotoxicity by inhibiting or promoting cell death in order to suppress innate immune function or to establish a replicative niche. Finally, an important mechanism common to many secreted effectors is the manipulation of host immune signaling. Until recently, fully evaluating the functional targets of bacterial secretion in vivo during infection was extremely difficult. FRET-Based β-lactamase Substrates as a Molecular Biology Tool Förster (fluorescence) resonance energy transfer (FRET) has been used extensively as a cell biology tool to monitor the dynamics of intermolecular interactions within cells. FRET employs a donor fluorophore and an acceptor fluorophore in close proximity, and the emission spectra of the donor overlaps with the absorption spectrum of the acceptor. Excitation of the donor fluorophore results in resonance energy transfer to, and emission from, the acceptor. Disruption of the proximity between the two fluorophores results in strong emission from the donor upon excitation. The utility of FRET for measuring inter-and intramolecular interactions has been evident for some time. Using fluorescence as a measure of proximity, fluorophores exhibiting FRET can be incorporated to measure protein-folding dynamics in real time. Further, labeling separate molecules allows for measuring protein-protein interactions, the distance between molecules, and determining protein localization within a cell. In 1998, Zlokarnik et al. used the gene encoding a common β-lactamase along with a FRETbased substrate to isolate individual cells with defined transcriptional responses from within a population of mammalian cells [1]. Zlokarnik et al. designed and synthesized the membranepermeant ester CCF2/AM, which consists of a 7-hydroxycoumarin donor fluorophore and a fluorescein acceptor linked by a cephalosporin antibiotic. In the intact molecule, donor excitation at 405 nm (violet light) will result in fluorescein acceptor emission as green light at 520 nm that can be detected using flow cytometry or fluorescence microscopy. In the presence of PLOS Pathogens |
doi:10.1371/journal.ppat.1004981 pmid:26247771 pmcid:PMC4527701 fatcat:w6gikcmjpvcn5ofsiv646bstoe

The spectrum of cognitive impairment in Lewy body diseases

Jennifer G. Goldman, Caroline Williams-Gray, Roger A. Barker, John E. Duda, James E. Galvin
2014 Movement Disorders  
comprehensive assessment required) Single domain: abnormalities on two tests within a single cognitive domain Multiple domain: abnormalities on at least 1 test in 2 or more domains Adapted from Litvan I, Goldman  ... 
doi:10.1002/mds.25866 pmid:24757110 pmcid:PMC4126402 fatcat:6r7utskjhrddhhe3kylb3bcyi4

The Yersinia pestis GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague

Samantha D. Crane, Srijon K. Banerjee, Kara R. Eichelberger, Richard C. Kurten, William E. Goldman, Roger D. Pechous, Igor E. Brodsky
2020 Infection and Immunity  
Y. pestis strain CO92, CO92 DbipA, and CO92 DpCD1 were obtained from the lab of William Goldman (UNC-Chapel Hill).  ...  Bacterial burdens were determined at 6 (A) and 12 (E) hpi by plating serial dilutions of organ homogenates on BHI agar plates.  ... 
doi:10.1128/iai.00673-20 fatcat:xxucswcpgzbp5mr6oqdc2z5s74

Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague

Nikolas M. Stasulli, Kara R. Eichelberger, Paul A. Price, Roger D. Pechous, Stephanie A. Montgomery, Joel S. Parker, William E. Goldman
2015 mBio  
This work was supported by National Institutes of Health grants AI099698 and AI057157 to William E. Goldman.  ...  (D and E) Representative images of a lung section before (D) and after (E) laser capture microdissection. The scale bar equals 300 m.  ...  Inoculation with nonpathogenic E. coli resulted in survival of only 20 to 30% of the initial population.  ... 
doi:10.1128/mbio.01530-15 pmid:26463167 pmcid:PMC4620470 fatcat:ev3b54n6enhgjgahxf3ibvx77u

Early Host Cell Targets of Yersinia pestis during Primary Pneumonic Plague

Roger D. Pechous, Vijay Sivaraman, Paul A. Price, Nikolas M. Stasulli, William E. Goldman, Barbara I. Kazmierczak
2013 PLoS Pathogens  
Acknowledgments We thank Joan Mecsas for supplying plasmid pSR47s-E-TEM and the UNC Microbiology and Immunology Flow Cytometry Core Facility for equipment and training.  ...  Plasmid pSR47s-E-TEM was transferred into Y. pestis CO92 from Escherichia coli S17 harboring pSR47-E-TEM via bacterial conjugation in the presence of 10 mM MgSO 4 , followed by growth on BHI agar containing  ...  Mice were inoculated with 10 6 CFU Y. pestis and lungs were inflated with 10% formalin at 24 and 48 hpi prior to H and E staining.  ... 
doi:10.1371/journal.ppat.1003679 pmid:24098126 pmcid:PMC3789773 fatcat:ideqfzabkvffzj5vmcyv7yzozm

In Vivo Transcriptional Profiling of Yersinia pestis Reveals a Novel Bacterial Mediator of Pulmonary Inflammation

Roger D. Pechous, Christopher A. Broberg, Nikolas M. Stasulli, Virginia L. Miller, William E. Goldman
2015 mBio  
Citation Pechous RD, Broberg CA, Stasulli NM, Miller VL, Goldman WE. 2015.  ...  (E) Total area of inflammation per lung section of infected mice.  ...  Three 5-micrometer sections 200 m apart per lung were stained with hematoxylin-eosin (H&E) for examination.  ... 
doi:10.1128/mbio.02302-14 pmid:25691593 pmcid:PMC4337571 fatcat:t7xmwmqqezgmbdvylacwlekmru

The Yersinia pestis GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague

Samantha D Crane, Srijon K Banerjee, Kara R Eichelberger, Richard C Kurten, William E Goldman, Roger D Pechous
2020 Infection and Immunity  
Cabanel N, Bouchier C, Rajerison M, Carniel E. 2017.  ...  Studies from multiple labs using E. coli in low temperature conditions showed 259 that BipA promotes efficient assembly of ribosomal proteins (25, 37).  ... 
doi:10.1128/iai.00673-20 pmid:33257531 fatcat:mmcmkgrewnenndd6e525ctq2bm

Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11)

Jason Fangusaro, Sridharan Gururangan, Tina Young Poussaint, Roger E. McLendon, Arzu Onar-Thomas, Katherine E. Warren, Shengjie Wu, Roger J. Packer, Anu Banerjee, Richard J. Gilbertson, Regina Jakacki, Amar Gajjar (+6 others)
2013 Cancer  
Efficacy data for patients enrolled on strata A, B, D, and E have been previously reported [34] [35] [36] . Stratum C was prematurely closed due to slow accrual.  ...  Over a third of the patients with low grade gliomas who were enrolled on stratum E had longer exposure to BVZ than patients on the pediatric phase I study 48 .  ... 
doi:10.1002/cncr.28343 pmid:24104527 pmcid:PMC3835419 fatcat:e72225d67zdbbo3rmziovbeqwm

Modeling the signature of sulfur mass-independent fractionation produced in the Archean atmosphere

Mark W. Claire, James F. Kasting, Shawn D. Domagal-Goldman, Eva E. Stüeken, Roger Buick, Victoria S. Meadows
2014 Geochimica et Cosmochimica Acta  
Fig. 9 . 9 Dresser Formation Barite crystals (photo credit -Roger Buick).  ...  Fig. 8 . 8 (a and c) Process-independent SO 2 photolysis fractionation factors ( 33 E k ) (Danielache et al., 2008; Ueno et al., 2009 ) (left axis, orange curves) and a laser transmission functions (right  ... 
doi:10.1016/j.gca.2014.06.032 fatcat:hooianypyvcthlraoeia7w4fgi

A learning algorithm for visual pose estimation of continuum robots

Austin Reiter, Roger E. Goldman, Andrea Bajo, Konstantinos Iliopoulos, Nabil Simaan, Peter K. Allen
2011 2011 IEEE/RSJ International Conference on Intelligent Robots and Systems  
The orientation of the end disk is given by the following sequence of rotations: R = R z R y R T z ( 2 ) where R z = e −δ [e 3 ×] , R y = e (θ 0 −θ L )[e 2 ×] , denote the exponential forms for these rotations  ...  ∈ R m×k , where the columns of E are each of the k basis vectors e representing the top k eigenvalues of the PCA.  ... 
doi:10.1109/iros.2011.6094947 dblp:conf/iros/ReiterGBISA11 fatcat:tsw3axrfljdkrdfmleeusho4gq

Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas—a Pediatric Brain Tumor Consortium study

Sridharan Gururangan, Jason Fangusaro, Tina Young Poussaint, Roger E. McLendon, Arzu Onar-Thomas, Shengjie Wu, Roger J. Packer, Anu Banerjee, Richard J. Gilbertson, Frederic Fahey, Sridhar Vajapeyam, Regina Jakacki (+7 others)
2013 Neuro-Oncology  
Background. A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival. Methods. Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies
more » ... luded neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2a, and carbonic anhydrase 9). Results. Thirty-five evaluable patients (median age 8.4 y [range, 0.6-17.6]) received a median of 12 courses of BVZ + CPT-11 (range, 2 -26). Twenty-nine of 35 patients (83%) received treatment for at least 6 months. Eight patients progressed on treatment at a median time of 5.4 months (range, 1 -17.8). Six patients (17.7%) still in follow-up have had stable disease without receiving additional treatment for a median of 40.1 months (range, 30.6-49.3) from initiating therapy. The 6-month and 2-year progression-free survivals were 85.4% (SE+5.96%) and 47.8% (SE+9.27%), respectively. The commonest toxicities related to BVZ included grades 1 -2 hypertension in 24, grades 1-2 fatigue in 23, grades 1 -2 epistaxis in 18, and grades 1 -4 proteinuria in 15. The median volume of enhancement decreased significantly between baseline and day 15 (P , .0001) and over the duration of treatment (P , .037). Conclusion. The combination of BVZ + CPT-11 appears to produce sustained disease control in some children with recurrent low-grade gliomas.
doi:10.1093/neuonc/not154 pmid:24311632 pmcid:PMC3895377 fatcat:ibl3fwaxobdnlpqkdh6b7myuee

A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study

Katherine E. Warren, Sri Gururangan, J. Russell Geyer, Roger E. McLendon, Tina Young Poussaint, Dana Wallace, Frank M. Balis, Stacey L. Berg, Roger J. Packer, Stewart Goldman, Jane E. Minturn, Ian F. Pollack (+2 others)
2011 Journal of Neuro-Oncology  
Purpose-To estimate the sustained (≥8 weeks) objective response rate in pediatric patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or brainstem gliomas (BSG, Stratum B) treated with the combination of O6-benzylguanine (O6BG) and temozolomide® (TMZ). Patients and Methods-Patients received O6BG 120 mg/m 2 /d IV followed by TMZ 75 mg/ m 2 /d orally daily for 5 consecutive days of each 28-day course. The target objective response rate to consider the combination active was
more » ... 17%. A two-stage design was employed. Results-Forty-three patients were enrolled; 41 were evaluable for response, including 25 patients with HGG and 16 patients with BSG. The combination of O6BG and TMZ was tolerable, and the primary toxicities were myelosuppression and gastrointestinal symptoms. One sustained (≥8 weeks) partial response was observed in the HGG cohort; no sustained objective responses were observed in the BSG cohort. Long-term (≥6 courses) stable disease (SD) was observed in 4 patients in Stratum A and 1 patient in Stratum B. Of the 5 patients with objective response or longterm SD, 3 underwent central review with 2 reclassified as low-grade gliomas. Conclusions-The combination of O6BG and TMZ did not achieve the target response rate for activity in pediatric patients with recurrent or progressive HGG and BSG.
doi:10.1007/s11060-011-0709-z pmid:21968943 pmcid:PMC3518022 fatcat:yohigv5bxzaspgvlnqwwvdy2qm

Targeted gene delivery to Kaposi's sarcoma cells via the fibroblast growth factor receptor

C K Goldman, B E Rogers, J T Douglas, B A Sosnowski, W Ying, G P Siegal, A Baird, J A Campain, D T Curiel
1997 Cancer Research  
C, E. and G) or nonimmune control (B, D, F, and H). Fig. 3 . 3 Enhanced AdCMVLuc infectivity of KS cell lines by Fab-FGF2 conjugate.  ...  Phone: (205) 934-8627; Fax: (205) 975-7476; E-mail: david.curiel@ 3 The abbreviations used are: KS, Kaposi's sarcoma; FGF.  ... 
pmid:9108444 fatcat:koi5c43fvbh2do7sj4ocdinncu

Design and Coordination Kinematics of an Insertable Robotic Effectors Platform for Single-Port Access Surgery

Jienan Ding, Roger E. Goldman, Kai Xu, Peter K. Allen, Dennis L. Fowler, Nabil Simaan
2013 IEEE/ASME transactions on mechatronics  
direct kinematics G 2 p e/g 2 = e − g 2 ê 3 , G 2 R E = e q 7 [ê 3 ] . (33) E.  ...  (30) B i R G i = e −δ i [ê 3 ] e ( π 2 −θ i )[ê2 ] e δ i [ê 3 ] , i = 1, 2 (31) whereê i (i = 1, 2, 3) are basis unit vectors for R 3×1 .  ... 
doi:10.1109/tmech.2012.2209671 pmid:23963105 pmcid:PMC3744894 fatcat:b2klxybanjfc5gwg5mu67lj2ym

Glioma Stem Cell Proliferation and Tumor Growth Are Promoted by Nitric Oxide Synthase-2

Christine E. Eyler, Qiulian Wu, Kenneth Yan, Jennifer M. MacSwords, Devin Chandler-Militello, Katherine L. Misuraca, Justin D. Lathia, Michael T. Forrester, Jeongwu Lee, Jonathan S. Stamler, Steven A. Goldman, Markus Bredel (+4 others)
2011 Cell  
(E).  ...  Within GSCs and non-GSCs, we employed lentiviralbased expression of the E. coli FlavoHb.  ... 
doi:10.1016/j.cell.2011.06.006 pmid:21729780 pmcid:PMC3144745 fatcat:ynle3edeiffdhnpb5g56zydzlm
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