Kwang Sik Kim

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (162)606.24 Total impact

  • Carine Tarazi, Carlo Agostoni, Kwang Sik Kim
    Pediatric research. 07/2014;
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    ABSTRACT: The mosquito-borne West Nile virus (WNV) is responsible for outbreaks of viral encephalitis in humans, horses and birds with particularly virulent strains causing recent outbreaks of disease in Eastern Europe, the Middle East, North America and Australia. Previous studies have phylogenetically separated WNV strains into two main genetic lineages (I and II), containing virulent strains associated with neurological disease. Several WNV-like strains, clustering outside these lineages have been identified and form an additional five proposed lineages. However, little is known about whether these strains have the potential to induce disease. In a comparative analysis with the highly virulent Lineage I American strain (WNVNY99), the low pathogenic Lineage II strain (B956) and a benign Australian strain, Kunjin (WNVKUN); the African WNV-like Koutango virus (WNVKOU) and a WNV-like isolate from Sarawak, Malaysia (WNVSarawak) were assessed for neuroinvasive properties in a murine model and for their replication kinetics in vitro. While WNVNY99 replicated to highest levels in vitro, in vivo mouse challenge revealed that WNVKOU was more virulent with a shorter time to onset of neurological disease and higher morbidity. Histological analysis of WNVKOU- and WNVNY99-infected brain and spinal cords demonstrated a more prominent meningoencephalitis and presence of viral antigen in WNVKOU-infected mice. Enhanced virulence of WNVKOU was also associated with poor viral clearance in the periphery (sera and spleen), a skewed innate immune response and poor neutralizing antibody development. These data demonstrate for the first time potent neuroinvasive and neurovirulent properties of a WNV-like virus outside of Lineage I and II.
    Journal of virology. 06/2014;
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    ABSTRACT: Though many essential oils from citrus peels are claimed to have several medicinal functions, the chemical composition and biological activities of the essential oils of Citrus flowers have not been well described. Therefore, this study intended to investigate the chemical composition and anti-inflammatory potential of essential oils from C. unshiu flower (CEO) to support its purported beneficial health effects. The chemical constituents of the CEO, analyzed by gas chromatography-mass spectrometry (GC-MS), included y-terpinene (24.7%), 2-beta-pinene (16.6%), 1-methyl-2-isopropylbenzene (11.5%), L-limonene (5.7%), beta3-ocimene (5.6%), and alpha-pinene (4.7%). The effects of the CEO on nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. The results indicate that the CEO is an effective inhibitor of LPS-induced NO and PGE2 production in RAW 264.7 cells. Additionally, CEO was shown to suppress the production of inflammatory cytokines including interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6. Based on these results, CEO may be considered a potential anti-inflammatory candidate with human health benefits.
    Natural product communications 05/2014; 9(5):727-30. · 0.96 Impact Factor
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    ABSTRACT: Cronobacter sakazakii is a foodborne pathogen, which causes a life-threatening form of meningitis, necrotizing colitis and meningoencephalitis in neonates and children. Epidemiological studies implicate dried infant formula as the principal source of C. sakazakii. In this study, we investigated the efficacy of sub-inhibitory concentrations (SIC) of trans-cinnamaldehyde (TC), an ingredient in cinnamon, for reducing C. sakazakii virulence in vitro using cell culture, microscopy and gene expression assays. TC significantly (p ≤ 0.05) suppressed C. sakazakii adhesion to and invasion of human and rat intestinal epithelial cells, and human brain microvascular endothelial cells. In addition, TC inhibited C. sakazakii survival and replication in human macrophages. We also observed that TC reduced the ability of C. sakazakii to cause cell death in rat intestinal cells, by inhibiting nitric oxide production. Results from gene expression studies revealed that TC significantly downregulated the virulence genes critical for motility, host tissue adhesion and invasion, macrophage survival, and LPS (Lipopolysaccharide) synthesis in C. sakazakii. The efficacy of TC in attenuating these major virulence factors in C. sakazakii underscores its potential use in the prevention and/or control of infection caused by this pathogen.
    International Journal of Molecular Sciences 01/2014; 15(5):8639-55. · 2.46 Impact Factor
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    ABSTRACT: Enterohemorrhagic Escherichia coli (EHEC) strains cause diarrhea and hemolytic uremic syndrome resulting from toxin-mediated microvascular endothelial injury. EHEC hemolysin (EHEC-Hly), a member of the RTX (repeats-in-toxin) family, is an EHEC virulence factor of increasingly recognized importance. The toxin exists as free EHEC-Hly and as EHEC-Hly associated with outer membrane vesicles (OMVs) released by EHEC during growth. Whereas the free toxin is lytic towards human endothelium, the biological effects of the OMV-associated EHEC-Hly on microvascular endothelial and intestinal epithelial cells, which are the major targets during EHEC infection, are unknown. Using microscopic, biochemical, flow cytometry and functional analyses of human brain microvascular endothelial cells (HBMEC) and Caco-2 cells we demonstrate that OMV-associated EHEC-Hly does not lyse the target cells but triggers their apoptosis. The OMV-associated toxin is internalized by HBMEC and Caco-2 cells via dynamin-dependent endocytosis of OMVs and trafficked with OMVs into endo-lysosomal compartments. Upon endosome acidification and subsequent pH drop, EHEC-Hly is separated from OMVs, escapes from the lysosomes, most probably via its pore-forming activity, and targets mitochondria. This results in decrease of the mitochondrial transmembrane potential and translocation of cytochrome c to the cytosol, indicating EHEC-Hly-mediated permeabilization of the mitochondrial membranes. Subsequent activation of caspase-9 and caspase-3 leads to apoptotic cell death as evidenced by DNA fragmentation and chromatin condensation in the intoxicated cells. The ability of OMV-associated EHEC-Hly to trigger the mitochondrial apoptotic pathway in human microvascular endothelial and intestinal epithelial cells indicates a novel mechanism of EHEC-Hly involvement in the pathogenesis of EHEC diseases. The OMV-mediated intracellular delivery represents a newly recognized mechanism for a bacterial toxin to enter host cells in order to target mitochondria.
    PLoS Pathogens 12/2013; 9(12):e1003797. · 8.14 Impact Factor
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    ABSTRACT: The blood-brain barrier (BBB) formed by brain capillary endothelial cells (BCECs) constitutes a firm physical, chemical and immunological barrier making the brain accessible to only a few percent of potential drugs intended for treatment inside the central nervous system (CNS). With the purpose of overcoming the restraints of the BBB by enabling transport of drugs, siRNA or DNA into the brain, a novel approach is to use superparamagnetic iron oxide nanoparticles (SPIONs) as drug-carriers. The aim of this study was to investigate the ability of fluorescent SPIONs to pass through human brain microvascular endothelial cells (HBMEC) facilitated by an external magnet. The capability of SPIONs to penetrate the barrier was shown to be significantly higher in the presence of an external magnetic force in an in vitro BBB model. Hence, particles added to the luminal side of the in vitro BBB model were found in astrocytes co-cultured in remote distance on the abluminal side, indicating that particles were transported through the barrier and taken up by astrocytes. Addition of the SPIONs to the culture medium did not negatively affect the viability of the endothelial cells. The magnetic force-mediated dragging of SPIONs through BCECs may denote a novel mechanism for drug delivery to the brain.
    ACS Chemical Neuroscience 08/2013; · 3.87 Impact Factor
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    ABSTRACT: To investigate the suitability of citrus-press cakes, by-products of the juice industry as a source for the whitening agents for cosmetic industry. Ethylacetate extracts of citrus-press cakes (CCE) were examined for their anti-melanogenic potentials in terms of the inhibition of melanin production and mechanisim of melanogenesis by using Western Blot analysis with tyrosinese, tyrosinase-related protein-1 (TRP-1), TRP2, and microphthalmia-associated transcription factor (MITF) proteins. To apply the topical agents, citrus-press cakes was investigated the safety in human skin cell line. Finally flavonoid analysis of CCE was also determined by HPLC analysis. Results indicated that CCE were shown to down-regulate melanin content in a dose-dependent pattern. The CCE inhibited tyrosinase, TRP-2, and MITF expressions in a dose-dependent manner. To test the applicability of CCE to human skin, we used MTT assay to assess the cytotoxic effects of CCE on human keratinocyte HaCaT cells. The CCE exhibited low cytotoxicity at 50 µg/mL. Characterization of the citrus-press cakes for flavonoid contents using HPLC showed varied quantity of rutin, narirutin, and hesperidin. Considering the anti-melanogenic activity and human safety, CCE is considered as a potential anti-melanogenic agent and may be effective for topical application for treating hyperpigmentation disorders.
    Asian Pacific Journal of Tropical Biomedicine 08/2013; 3(8):617-22.
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    ABSTRACT: Group B Streptococcus (GBS) is the leading cause of meningitis in neonates. We have previously shown that plasminogen, once recruited to the GBS cell surface and converted into plasmin by host-derived activators, leads to an enhancement of bacterial virulence. Here, we investigated whether plasmin(ogen) bound at the GBS surface contributes to blood-brain barrier penetration and invasion of the central nervous system. For that purpose, GBS strain NEM316 preincubated with or without plasminogen plus tissue type plasminogen activator was analyzed for the capacity to adhere to, invade and transmigrate the human brain microvascular endothelial cell (hBMEC) monolayer, and to penetrate the central nervous system using a neonatal mouse model. At earlier times of infection, plasmin(ogen)-treated GBS exhibited a significant increase in adherence to and invasion of hBMECs. Later, injury of hBMECs were observed with plasmin(ogen)-treated GBS that displayed a plasmin-like activity. The same results were obtained when hBMECs were incubated with whole human plasma and infected with untreated GBS. To confirm that the observed effects were due to the recruitment and activation of plasminogen on GBS surface, the bacteria were first incubated with epsilon-aminocaproic acid (εACA), an inhibitor of plasminogen binding, and thereafter with plasmin(ogen). A significant decrease in the hBMECs injury that was correlated with a decrease of the GBS surface proteolytic activity was observed. Furthermore, plasmin(ogen)-treated GBS infected more efficiently the brain of neonatal mice than the untreated bacteria, indicating that plasmin(ogen) bound to GBS surface may facilitate the traversal of the blood-brain barrier. A higher survival rate was observed in offspring born from εACA-treated mothers, compared to untreated mice, and no brain infection was detected in these neonates. Our findings suggest that capture of the host plasmin(ogen) by the GBS surface promotes the crossing of the blood-brain barrier and contributes to the establishment of meningitis.
    PLoS ONE 01/2013; 8(5):e63244. · 3.53 Impact Factor
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    ABSTRACT: While a wealth of literature for tissue-specific liposomes is emerging, optimal formulations to target the cells of the peripheral nervous system (PNS) are lacking. In this study, we asked whether a novel formulation of phospholipid-based liposomes could be optimized for preferential uptake by microvascular endothelia, peripheral neurons and Schwann cells. Here, we report a unique formulation consisting of a phospholipid, a polymer surfactant and cholesterol that result in enhanced uptake by targeted cells. Using fluorescently labeled liposomes, we followed particle internalization and trafficking through a distinct route from dextran and escape from degradative compartments, such as lysosomes. In cultures of non-myelinating Schwann cells, liposomes associate with the lipid raft marker Cholera toxin, and their internalization is inhibited by disruption of lipid rafts or actin polymerization. In contrast, pharmacological inhibition of clathrin-mediated endocytosis does not significantly impact liposome entry. To evaluate the efficacy of liposome targeting in tissues, we utilized myelinating explant cultures of dorsal root ganglia and isolated diaphragm preparations, both of which contain peripheral neurons and myelinating Schwann cells. In these models, we detected preferential liposome uptake into neurons and glial cells in comparison to surrounding muscle tissue. Furthermore, in vivo liposome administration by intramuscular or intravenous injection confirmed that the particles were delivered to myelinated peripheral nerves. Within the CNS, we detected the liposomes in choroid epithelium, but not in myelinated white matter regions or in brain parenchyma. The described nanoparticles represent a novel neurophilic delivery vehicle for targeting small therapeutic compounds, biological molecules, or imaging reagents into peripheral neurons and Schwann cells, and provide a major advancement toward developing effective therapies for peripheral neuropathies.
    PLoS ONE 01/2013; 8(11):e78724. · 3.53 Impact Factor
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    Ming-Hsien Wang, Kwang Sik Kim
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    ABSTRACT: E. coli is the most common Gram-negative bacteria causing neonatal meningitis, and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Recent reports of E. coli meningitis caused by antimicrobial resistant strains are a particular concern. These findings indicate that a novel strategy is needed to identify new targets for prevention and therapy of E. coli meningitis. Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor associated principally with E. coli strains causing urinary tract infection and meningitis. We have shown that CNF1 contributes to E. coli invasion of the blood-brain barrier and penetration into the brain, the essential step in the development of E. coli meningitis, and identified the host receptor for CNF1, 37-kDa laminin receptor precursor (37LRP). CNF1, however, is a cytoplasmic protein and its contribution to E. coli invasion of the blood-brain barrier requires its secretion from the bacterial cytoplasm. No signal peptide is found in the CNF1 sequence. CNF1 secretion is, therefore, a strategy utilized by meningitis-causing E. coli to invade the blood-brain barrier. Elucidation of the mechanisms involved in CNF1 secretion, as shown in this report with the involvement of Fdx and YgfZ provides the novel information on potential targets for prevention and therapy of E. coli meningitis by virtue of targeting the secretion of CNF1.
    Toxins 01/2013; 5(11):2270-2280. · 2.13 Impact Factor
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    ABSTRACT: This study was designed to analyze the chemical composition of essential oil in 'Shiranuhi' immature fruit and to test their biological activities. 'Shiranuhi' immature essential oils (SIEO) were obtained by steam distillation from fruits collected from Jeju Island and were analyzed using gas chromatograph (GC)-flame ionization detectors (FID) and GC-MS. Fourteen components were identified in the essential oil. Limonene (75.21%) and terpineol (8.68%) were the major components in SIEO. Since acne vulgaris is the combined result of a bacterial infection and the inflammatory response to that infection, we examined whether SIEO possessed antibacterial against skin pathogens. As a result, SIEO showed excellent antibacterial activities against drug-susceptible and -resistant Propionibacterium acnes and Staphylococcus epidermidis, which are acne-causing bacteria. In this study, SIEO was examined on DPPH radical scavenging activities, which showed moderate antioxidant activity (, ). In order to determined whether SIEO can be safely applied to human skin, the cytotoxicity effects of SIEO were determined by colorimetric MTT assays in normal human fibroblasts and keratinocyte HaCaT cells. They exhibited low cytotoxicity at in both celllines. Based on these results, we suggest the possibility that essential oil of 'Shiranuhi' maybe considered as an antibacterial and antioxidant agent.
    Korean Journal of Medicinal Crop Science. 01/2013; 21(6).
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    ABSTRACT: Tricellulin is a tight junction (TJ) protein, which is not only concentrated at tricellular contacts but also present at bicellular contacts between epithelial tissues. We scrutinized the brain for tricellulin expression in endothelial and neural cells by using real-time polymerase chain reaction, Western blot and immunohistochemical and immunocytochemical analysis of cultured brain cells and paraffin sections of brain. Tricellulin mRNA was detected in primary cultures and in a cell line of human brain microvascular endothelial cells. Protein expression was confirmed by Western blot and immunofluorescence analysis, which further highlighted the localization of tricellulin in the cell membrane at tricellular and along bicellular contacts, and in the nucleus and perinuclear region. Compared with the well-studied TJ protein, zonula occludens-1, tricellulin expression was less marked at the cell membrane but more evident in the nuclear and perinuclear regions. The presence of tricellulin in cultured endothelial cells was corroborated by immunohistochemical and immunofluorescence staining in brain blood vessels, where it was colocalized with another TJ protein, claudin-5. Tricellulin mRNA was detected in neurons and astrocytes, whereas protein expression was observed in astrocytes but not in neurons, as shown by immunofluorescence analysis. This study reveals the presence and subcellular distribution of tricellulin in brain endothelial cells, both in vitro and in situ and its colocalization with other relevant TJ proteins. Moreover, it demonstrates the expression of the protein in astrocytes opening new avenues for future research to establish the biological significance of tricellulin expression in glial cells.
    Cell and Tissue Research 12/2012; · 3.68 Impact Factor
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    Dataset: CE10vsIAI39
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    Dataset: CE10vsS88
  • Seon Hee Shin, Kwang Sik Kim
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    ABSTRACT: Introduction: The introduction of protein conjugate vaccines for Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (S. pneumoniae) and Neisseria meningitidis (N. menigitidis) has changed the epidemiology of bacterial meningitis. Bacterial meningitis continues to be an important cause of mortality and morbidity, and our incomplete knowledge of its pathogenesis and emergence of antimicrobial resistant bacteria contribute to such mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis. Areas covered: This article gives an overview on optimal treatment strategies of bacterial meningitis, along with considerations of new insights on epidemiology, clinical and laboratory findings supportive of bacterial meningitis, chemoprophylaxis, selection of initial antimicrobial agents for suspected bacterial meningitis, antimicrobial resistance and utility of new antibiotics, status on anti-inflammatory agents and adjunctive therapy, and pathogenesis of bacterial meningitis. Expert opinion: Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood-brain barrier (BBB), with efficacy in cerebrospinal fluid (CSF). Several new antibiotics have been introduced for the treatment of meningitis caused by resistant bacteria, but their use in human studies has been limited. More complete understanding of the microbial and host interactions that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.
    Expert Opinion on Pharmacotherapy 10/2012; 13(15):2189-206. · 2.86 Impact Factor
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    ABSTRACT: The type IV pilus of Neisseria meningitidis is the major factor for meningococcal adhesion to host cells. In this study, we showed that a mutant of N. meningitidis pilV, a minor pilin protein, internalized less efficiently to human endothelial and epithelial cells than the wild type strain. MALDI-TOF MS and ESI-MS/MS analyses showed that PilE, the major subunit of pili, was less glycosylated at its Serine 62 residue (Ser62) in ΔpilV mutant than in the pilV(+) strain, while phosphoglycerol at PilE Ser93 and phosphocholine at PilE Ser67 were not changed. Introduction of the pglL mutation, which results in complete loss of O-linked glycosylation from Ser62, slightly reduced N. meningitidis internalization into human brain microvasocular endothelial cells, while addition of the ΔpilV mutation greatly reduced N. meningitidis internalization. The accumulation of ezrin, which is part of the cytoskeleton ERM family, was observed with pilV(+), pglL(-) and pilES62A strains, but not with the ΔpilV mutant. These results suggested that, while N. meningitidis pilin originally had an adhesive activity that was less affected by minor pilin proteins, the invasive function evolved with incorporation of the PilV protein into the pili to promote the N. meningitidis internalization into human cells.
    Infection and immunity 09/2012; · 4.21 Impact Factor
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    ABSTRACT: Extraintestinal Escherichia coli (ExPEC), a heterogeneous group of pathogens, encompasses avian, neonatal meningitis, and uropathogenic E. coli strains. While several virulence factors are associated with ExPEC, there is no core set of virulence factors that can be used to definitively differentiate these pathotypes. Here we describe a multiplex of four virulence factor-encoding genes, yfcV, vat, fyuA, and chuA, highly associated with uropathogenic E. coli, can distinguish three groups of E. coli: diarrheagenic and animal-associated E. coli, human commensal and avian pathogenic E. coli, and uropathogenic and neonatal meningitis E. coli. Furthermore, human intestinal isolates that encode all four predictor genes express them during exponential growth in human urine and colonize the bladder in the mouse model of ascending urinary tract infection in higher numbers than human commensal strains that do not encode the four predictor genes (P = 0.02), suggesting that the presence of the predictors correlates with uropathogenic potential.
    Infection and immunity 09/2012; · 4.21 Impact Factor
  • Jun-Hong Kim, Kwang Sik Kim
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    ABSTRACT: Alcohol-related motor vehicle collisions have been the top of policy agenda for more than three decades in Korea. Despite implementation of various traffic safety measures, some drivers' alcohol use and abuse has resulted in a high number of alcohol-impaired traffic fatalities every year. This paper presents the association of theoretical factors with behavior of riding with an alcohol-impaired driver (RAID) among all age groups in the Korean adult sample. The theoretical factors of the drivers are personality factor, socio-psychological factor, and alcohol-related behavioral risk factor. We utilized national survey data from 1007 respondents consisting of 703 males and 304 females aged 20-66 collected by Korean Institute of Criminology (KIC) to test our theorized model. Our results indicated that there were three major predictors of RAID involvement: sensation seeking propensity, perceived peer pressure, and frequent harmful drinking. Overall, prediction of RAID behavior by gender was mediated entirely through these predictors. The issue of males' higher risk of RAID involvements was addressed for effective communication strategies such as campaigns.
    Accident; analysis and prevention 09/2012; 48:326-34. · 1.65 Impact Factor
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    ABSTRACT: Acanthamoeba castellanii is a single-celled protozoan that is widely distributed in the environment and is a well-known of causing human keratitis, a vision-threatening infection. In this study, an ethyl methane sulfonate (EMS) and a selection of saccharide were applied to A. castellanii by chemical mutagenesis. To understand the functional roles of a mannose-binding protein (MBP). A. castellanii were treated with methyl-alpha-d-mannopyranoside abbreviated Man, with and without the EMS pre-treatment, and their adhesion and cytotoxicity were analyzed, using a human brain microvascular endothelial cell (HBMEC) as the target cell. Both EMS and Man mutants exhibited significantly decreased levels of MBP expression and cytotoxicity to HBMEC, but showed similar levels of binding to HBMEC, as compared with the wild type. Of interest was that the exogenous mannose inhibited amoebae (i.e., Man mutant) binding to the HBMEC by <20%. Only the mutant Man exhibited a significant decrease in bacterial uptake, as compared to the wild type, 0.020 vs 0.032 (p<0.05) and proteolytic activity. The results showed that MBP should be clearly provided as the pathogenic target candidate, to further target-based therapy, but EMS mutation should not be associated with initial adhesion and phagocytosis of A. castellanii.
    Experimental Parasitology 08/2012; 132(2):287-92. · 2.15 Impact Factor
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    ABSTRACT: Escherichia coli is a common Gram-negative organism that causes bacteremia. Prc, a bacterial periplasmic protease, and its homologues are known to be involved in the pathogenesis of Gram-negative bacterial infections. The present study examined the role of Prc in E. coli bacteremia and characterized the ability of the prc mutant of the pathogenic E. coli strain RS218 to cause bacteremia and survive in human serum. The prc mutant of RS218 exhibited a decreased ability to cause a high level of bacteremia and was more sensitive to serum killing than strain RS218. This sensitivity was due to the mutant's decreased ability to avoid the activation of the antibody-dependent and -independent classical complement cascades as well as its decreased resistance to killing mediated by the membrane attack complex, the end product of complement system activation. The demonstration of Prc in the evasion of classical complement-mediated serum killing of pathogenic E. coli makes this factor a potential target for the development of therapeutic and preventive measures against E. coli bacteremia.
    Infection and immunity 07/2012; 80(10):3399-409. · 4.21 Impact Factor

Publication Stats

4k Citations
606.24 Total Impact Points

Institutions

  • 2001–2014
    • Johns Hopkins University
      • • Department of Pediatrics
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 2012
    • Korea University
      • School of Media and Communication
      Seoul, Seoul, South Korea
    • Chang Gung Memorial Hospital
      • Division of Pediatric Infectious Diseases
      T’ai-pei, Taipei, Taiwan
  • 2006–2012
    • Sungkyunkwan University
      • Department of Public Administration
      Sŏul, Seoul, South Korea
    • National Health Research Institutes
      Miao-li-chieh, Taiwan, Taiwan
  • 2011
    • Shanghai Institutes for Biological Sciences
      Shanghai, Shanghai Shi, China
    • University of Seoul
      Sŏul, Seoul, South Korea
  • 2010
    • National Cheng Kung University Hospital
      臺南市, Taiwan, Taiwan
  • 2008–2010
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan
    • University of Wuerzburg
      • Institute for Virology and Immune Biology
      Würzburg, Bavaria, Germany
  • 2009
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
    • University of Connecticut
      • Department of Animal Science
      Storrs, CT, United States
  • 2005–2007
    • Birkbeck, University of London
      Londinium, England, United Kingdom
  • 2004–2007
    • University of London
      Londinium, England, United Kingdom
  • 2003–2007
    • Johns Hopkins Medicine
      • Department of Pediatrics
      Baltimore, Maryland, United States
  • 1997–2002
    • Children's Hospital Los Angeles
      • Division of Infectious Diseases
      Los Angeles, California, United States
  • 1996–2000
    • University of Southern California
      • Department of Pediatrics
      Los Angeles, California, United States
  • 1999
    • The University of Arizona
      • Department of Surgery
      Tucson, Arizona, United States
  • 1990
    • Walter Reed Army Institute of Research
      Silver Spring, Maryland, United States
    • Keck School of Medicine USC
      Los Angeles, California, United States
  • 1986
    • Harbor-UCLA Medical Center
      Torrance, California, United States