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1.
Int J Mol Sci ; 23(21)2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36361923

ABSTRACT

Acinetobacter baumannii expresses various virulence factors to adapt to hostile environments and infect susceptible hosts. This study investigated the regulatory network of the BfmRS two-component and AbaIR quorum sensing (QS) systems in the expression of virulence-associated genes in A. baumannii ATCC 17978. The ΔbfmS mutant exhibited a significant decrease in surface motility, which presumably resulted from the low expression of pilT and A1S_0112-A1S_0119 gene cluster. The ΔbfmR mutant displayed a significant reduction in biofilm and pellicle formation due to the low expression of csu operon. The deletion of abaR did not affect the expression of bfmR or bfmS. However, the expression of abaR and abaI was upregulated in the ΔbfmR mutant. The ΔbfmR mutant also produced more autoinducers than did the wild-type strain, suggesting that BfmR negatively regulates the AbaIR QS system. The ΔbfmS mutant exhibited no autoinducer production in the bioassay system. The expression of the A1S_0112-A1S_0119 gene cluster was downregulated in the ΔabaR mutant, whereas the expression of csu operon was upregulated in this mutant with a high cell density. In conclusion, for the first time, we demonstrated that the BfmRS-AbaIR QS system axis regulated the expression of virulence-associated genes in A. baumannii. This study provides new insights into the complex network system involved in the regulation of virulence-associated genes underlying the pathogenicity of A. baumannii.


Subject(s)
Acinetobacter baumannii , Virulence/genetics , Quorum Sensing/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biofilms , Gene Expression Regulation, Bacterial
2.
Infect Genet Evol ; 93: 104935, 2021 09.
Article in English | MEDLINE | ID: mdl-34029723

ABSTRACT

The expansion of specific carbapenem-resistant Acinetobacter baumannii (CRAB) clones is a global concern due to its therapeutic difficulty and epidemicity. To understand the prevalence of CRAB isolates in a Korean hospital, we investigated the epidemiological characteristics of 96 CRAB isolates between 2016 and 2018, including the sequence types (STs), antimicrobial susceptibility, and genetic background of resistance to carbapenems and aminoglycosides. Six STs were identified using the Oxford multilocus sequence typing scheme; ST191 (n = 8), ST208 (n = 12), ST229 (n = 11), and ST369 (n = 21) were previously identified clones in the study hospital, whereas gpi variants of ST208, ST451 (n = 34) and ST784 (n = 10), were emerging clones. ST208 isolates exhibited higher resistance rates to minocycline than other ST isolates, whereas ST369 isolates exhibited lower resistance rates to aminoglycosides and trimethoprim/sulfamethoxazole than other ST isolates. All CRAB isolates previously isolated in the study hospital carried ISAbaI-blaOXA-23 for carbapenem resistance, but 10 ST229 isolates carried only ISAbaI-blaOXA-51. The carriage of armA was lower in ST369 isolates (38%) than in other ST isolates (≥83%). The frequency and diversity of aminoglycoside-modifying enzyme genes were decreased among the CRAB isolates between 2016 and 2018 compared with CRAB isolates between 2013 and 2015 at the study hospital. In conclusion, clonal complex 208 CRAB isolates are predominant in the study hospital. This study demonstrates the evolutionary change of CRAB isolates in the study hospital in relation to the emergence of new STs and selection of resistant genes.


Subject(s)
Acinetobacter Infections/epidemiology , Acinetobacter baumannii/genetics , Aminoglycosides/pharmacology , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Drug Resistance, Bacterial/genetics , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Hospitals , Humans , Republic of Korea/epidemiology
3.
BMC Microbiol ; 21(1): 27, 2021 01 18.
Article in English | MEDLINE | ID: mdl-33461493

ABSTRACT

BACKGROUND: Zinc uptake-regulator (Zur)-regulated lipoprotein A (ZrlA) plays a role in bacterial fitness and overcoming antimicrobial exposure in Acinetobacter baumannii. This study further characterized the zrlA gene and its encoded protein and investigated the roles of the zrlA gene in bacterial morphology, antimicrobial susceptibility, and production of outer membrane vesicles (OMVs) in A. baumannii ATCC 17978. RESULTS: In silico and polymerase chain reaction analyses showed that the zrlA gene was conserved among A. baumannii strains with 97-100% sequence homology. Recombinant ZrlA protein exhibited a specific enzymatic activity of D-alanine-D-alanine carboxypeptidase. Wild-type A. baumannii exhibited more morphological heterogeneity than a ΔzrlA mutant strain during stationary phase. The ΔzrlA mutant strain was more susceptible to gentamicin than the wild-type strain. Sizes and protein profiles of OMVs were similar between the wild-type and ΔzrlA mutant strains, but the ΔzrlA mutant strain produced 9.7 times more OMV particles than the wild-type strain. OMVs from the ΔzrlA mutant were more cytotoxic in cultured epithelial cells than OMVs from the wild-type strain. CONCLUSIONS: The present study demonstrated that A. baumannii ZrlA contributes to bacterial morphogenesis and antimicrobial resistance, but its deletion increases OMV production and OMV-mediated host cell cytotoxicity.


Subject(s)
Acinetobacter baumannii/pathogenicity , Computational Biology/methods , Drug Resistance, Bacterial , Lipoprotein(a)/genetics , A549 Cells , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Acinetobacter baumannii/metabolism , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Computer Simulation , Extracellular Vesicles/metabolism , Gentamicins/pharmacology , Humans , Lipoprotein(a)/metabolism , Mutation , Zinc/metabolism
4.
Schizophr Res Cogn ; 23: 100192, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33294392

ABSTRACT

We investigated the relationship between disability self-awareness and cognitive and daily living functions in 49 patients with schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS) self-report was used to identify patient-rated global function. A clinician-rated measure of global function was obtained using the Personal and Social Performance Scale (PSP); disability self-awareness was calculated using two global function scores. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to evaluate clinical symptoms, while the MATRICS consensus cognitive battery (MCCB) and the UCSD Performance-based Skills Assessment (UPSA) were applied to assess cognitive and daily living functionality, respectively. The WHODAS scores correlated significantly with the MCCB verbal learning, visual learning, and social cognition domains, and with the UPSA communication domain. The PSP correlated significantly with all MCCB and UPSA domains. Disability self-awareness demonstrated positive correlation with most domains of MCCB and UPSA. The findings of this study indicate that the lower the cognitive and daily living function in patients with schizophrenia, the more positively they perceive their own disability.

5.
Schizophr Res ; 220: 172-178, 2020 06.
Article in English | MEDLINE | ID: mdl-32241751

ABSTRACT

We investigated the effect of an extrinsic motivator on the MATRICS Consensus Cognitive Battery (MCCB) and UCSD Performance-Based Skills Assessment (UPSA) scores, which assess cognitive and daily living functions, in patients with schizophrenia. We enrolled 60 clinically stable patients with schizophrenia and allocated them to the motivator or control group. We conducted baseline assessments of cognitive function using the MCCB, daily living function using the UPSA, clinical symptoms, and psychosocial characteristics in both groups. In the retrial, we initially evaluated clinical symptoms. Next, we assigned an extrinsic motivator to the motivator group and again assessed cognitive function and daily living function using the MCCB and UPSA. Statistical analyses were performed using t-tests, Chi-square tests, Fisher's exact test, repeated measures analysis of variance, and logistic regression analysis. We found significant time × group interactions in processing speed, verbal learning, visual learning, and composite scores of MCCB. There were no significant interactions in UPSA scores. The meaningful change rates of social cognition and composite scores in MCCB were significantly higher in the motivator group than in the control group. After adjusting for additional variables, the extrinsic motivator had a significant effect on the meaningful MCCB composite score change. Conclusively, our findings suggest beneficial effects of extrinsic motivator on the MCCB score in patients with schizophrenia. In the future, the implementation and interpretation of the MCCB considering the motivation is necessary.


Subject(s)
Cognition Disorders , Schizophrenia , Cognition , Humans , Neuropsychological Tests , Schizophrenia/complications , Schizophrenic Psychology
6.
BMC Microbiol ; 19(1): 301, 2019 12 21.
Article in English | MEDLINE | ID: mdl-31864291

ABSTRACT

BACKGROUND: Acinetobacter baumannii is an important opportunistic pathogen responsible for various nosocomial infections. The BfmRS two-component system plays a role in pathogenesis and antimicrobial resistance of A. baumannii via regulation of bacterial envelope structures. This study investigated the role of the sensor kinase, BfmS, in localization of outer membrane protein A (OmpA) in the outer membrane and production of outer membrane vesicles (OMVs) using wild-type A. baumannii ATCC 17978, ΔbfmS mutant, and bfmS-complemented strains. RESULTS: The ΔbfmS mutant showed hypermucoid phenotype in the culture plates, growth retardation under static culture conditions, and reduced susceptibility to aztreonam and colistin compared to the wild-type strain. The ΔbfmS mutant produced less OmpA in the outer membrane but released more OmpA via OMVs than the wild-type strain, even though expression of ompA and its protein production were not different between the two strains. The ΔbfmS mutant produced 2.35 times more OMV particles and 4.46 times more OMV proteins than the wild-type stain. The ΔbfmS mutant OMVs were more cytotoxic towards A549 cells than wild-type strain OMVs. CONCLUSIONS: The present study demonstrates that BfmS controls production of OMVs in A. baumannii. Moreover, BfmS negatively regulates antimicrobial resistance of A. baumannii and OMV-mediated host cell cytotoxicity. Our results indicate that BfmS negatively controls the pathogenic traits of A. baumannii via cell envelope structures and OMV production.


Subject(s)
Acinetobacter baumannii/genetics , Acinetobacter baumannii/pathogenicity , Bacterial Outer Membrane Proteins/genetics , Phosphotransferases/genetics , Secretory Vesicles/metabolism , Acinetobacter baumannii/enzymology , Bacterial Proteins/genetics , Gene Expression Regulation, Bacterial , Mutation , Phosphotransferases/metabolism
7.
Infect Genet Evol ; 58: 232-236, 2018 03.
Article in English | MEDLINE | ID: mdl-29307769

ABSTRACT

To elucidate the epidemicity of carbapenem-resistant Acinetobacter baumannii (CRAB), we investigated the antimicrobial susceptibility, the genetic basis of antimicrobial resistance, and the ability to form biofilms of 147 CRAB isolates collected between 2013 and 2015 from a Korean hospital based on sequence types (STs). Six different STs were identified: ST191 (n=47) and ST208 (n=36) were clones that had already been identified in the study hospital, whereas ST229 (n=28), ST369 (n=18), ST357 (n=17), and ST552 (n=1) were previously unknown. All the CRAB isolates exhibited an extensively drug-resistance. Twelve isolates, including ST191 and ST208, were resistant to tigecycline, and two were resistant to colistin. All the isolates carried ISAbaI-blaOXA-23 structures. The presence of the armA gene and/or a combination of aminoglycoside-modifying enzyme genes (aacC1, aadA1, aacA4, aphA1, and aphA6) was responsible for high-level resistance to aminoglycosides (minimal inhibitory concentrations≥256mg/L). All the ST229 isolates carried the blaPER-1 gene, whereas all the ST357 and ST369 isolates carried both aacA4 and aadA1. The ST229 isolates exhibited the greatest tendency to form biofilms, whereas the ST369 isolates exhibited significantly less tendency to form biofilms than other isolates. In conclusion, we discovered clonal diversity in the CRAB isolates from the study hospital. The resistant gene profiles and biofilm formation capabilities of the emerging CRAB STs differed from those of the circulating STs. The potential relationship between these genotypic and phenotypic traits and the epidemic capacity of CRAB STs requires further investigation.


Subject(s)
Acinetobacter Infections/epidemiology , Acinetobacter Infections/virology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Bacterial Proteins/genetics , Carbapenems/pharmacology , beta-Lactam Resistance , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Genotype , Humans , Multilocus Sequence Typing , Phenotype
8.
Curr Microbiol ; 73(4): 519-26, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27368232

ABSTRACT

Pseudomonas aeruginosa is a gram-negative bacterium that is frequently related to natural resistance to many drugs. In this work, the inhibition of growth against P. aeruginosa and multidrug-resistant P. aeruginosa (MDRPA) isolated from patients at Kyungpook National University was confirmed for hibicuslide C, essential oil components from Abutilon theophrasti. Hibicuslide C has antifungal activity with membrane disruption and apoptotic response against Candida albicans. However, its antibacterial activity was not reported yet. Cells treated with hibicuslide C was showed that its antipseudomonal activity is related to gDNA fragmentation and damage by TUNEL and gDNA electrophoresis. Furthermore, hibicuslide C worked synergistically with fluoroquinolones and rifampicin against MDRPA regardless of the ATP-associated mechanism. The antibiofilm activity possessed sole-resulting tissue culture plate method; besides that, the antibiofilm activity of other antibiotics was supported in particular MDRPA. The essential oil components like hibicuslide C may have antipseudomonal activity and, furthermore, increase in bacterial antibiotic susceptibility.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Magnoliopsida/chemistry , Oils, Volatile/pharmacology , Phenylpropionates/pharmacology , Plant Extracts/pharmacology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Biofilms/drug effects , Humans , Microbial Sensitivity Tests , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Pseudomonas aeruginosa/physiology
9.
Int J Syst Evol Microbiol ; 66(7): 2573-2577, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27088668

ABSTRACT

A Gram-stain-positive, catalase-positive, facultatively anaerobic, non-motile, coryneform bacterium, designated strain 32T, was isolated from a closed pus sample from a patient having finger necrosis in Korea. Strain 32T was considered as representing a novel species according to its initial identification by matrix-assisted laser desorption/ionization-time-of-flight MS. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 32T belonged to the genus Dermabacter and was closely related to Dermabacter hominis DSM 7083T (=ATCC 49369T) (98.34 % similarity). Optimal growth was observed at 30-40 °C and pH 7. Growth occurred in the presence of 0-6 % (w/v) NaCl. Menaquinones MK-8, MK-7 and MK-9 were the major respiratory quinones. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine, glycolipid and two unknown lipids. The major cellular fatty acids were anteiso-C17 : 0, anteiso-C15 : 0, iso-C16 : 0 and iso-C15 : 0. The DNA G+C content of strain 32T was 62.58 mol%, and the mean level of DNA-DNA relatedness between strain 32T and D. hominis ATCC 49369T was 49±1.6 %. Based on the phenotypic and genotypic characteristics, strain 32T is confirmed to represent a novel species of the genus Dermabacter, for which the name Dermabacter jinjuensis sp. nov. is proposed. The type strain is 32T (=NCCP 16133T=DSM 101003T).


Subject(s)
Actinomycetales/classification , Fingers/microbiology , Phylogeny , Suppuration/microbiology , Actinomycetales/genetics , Actinomycetales/isolation & purification , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Fingers/pathology , Humans , Necrosis , Nucleic Acid Hybridization , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Republic of Korea , Sequence Analysis, DNA , Vitamin K 2/chemistry
10.
J Microbiol ; 54(1): 44-49, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26727901

ABSTRACT

This study investigated the mechanisms underlying the carbapenem resistance of bloodstream isolates of Pseudomonas aeruginosa obtained from two Korean hospitals. Of the 79 P. aeruginosa isolates, 22 and 21 were resistant to imipenem and meropenem, respectively. The 22 imipenem-resistant P. aeruginosa isolates were classified into 7 sequence types (STs) and 13 pulsotypes. Twelve imipenem-resistant isolates from one hospital were found to belong to the international clone ST111. Two imipenem-resistant P. aeruginosa ST235 isolates carried the bla IMP-6 gene, but the remaining 20 isolates did not produce carbapenemases. Mutations in the oprD gene and a related decrease in gene expression were found in 21 and 5 isolates, respectively. However, all imipenemresistant P. aeruginosa isolates showed no significant expression of OprD in the outer membrane as compared with that of carbapenem-susceptible PAO1 strain. Overexpression of genes associated with efflux pumps, including mexB, mexD, mexF, and mexY, was not found in any imipenem-resistant isolate. One imipenem-resistant P. aeruginosa isolate overexpressed the ampC gene. Our results show that the low permeability of drugs due to the mutational inactivation of OprD is primarily responsible for carbapenem resistance in bloodstream isolates of P. aeruginosa from Korean hospitals.


Subject(s)
Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Porins/genetics , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Bacteremia/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Drug Resistance, Multiple, Bacterial/genetics , Humans , Imipenem/pharmacology , Meropenem , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , Mutation , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Pseudomonas aeruginosa/metabolism , Republic of Korea , Thienamycins/pharmacology , beta-Lactamases/genetics , beta-Lactamases/metabolism
11.
Virulence ; 7(4): 413-26, 2016 05 18.
Article in English | MEDLINE | ID: mdl-26759990

ABSTRACT

Acinetobacter nosocomialis is an important nosocomial pathogen that causes a variety of human infections. However, the specific virulence factors of this microorganism have not yet been determined. We investigated the role of outer membrane protein A (OmpA) in the pathogenesis of A. nosocomialis. A ΔompA mutant of the A. nosocomialis ATCC 17903(T) strain was constructed using markerless gene deletion. The ΔompA mutant displayed reduced biofilm formation in polystyrene tubes and reduced adherence to A549 cells in comparison to the wild-type strain. These virulence traits of the ΔompA mutant strain were restored when the ompA gene was complemented. Cytotoxicity was not significantly different between the wild-type strain and the ΔompA mutant when A549 cells were infected with bacteria or treated with outer membrane vesicles (OMVs). However, OMVs from the wild-type strain induced cytotoxicity in HEp-2 cells, whereas OMVs from the ΔompA mutant did not induce cytotoxicity. Proteomic analysis of OMVs revealed that OmpA influenced the distribution of envelope and periplasmic proteins. Overall, this study is the first report that links OmpA to A. nosocomialis pathogenesis, and highlights OmpA as a putative target to develop anti-virulence agents or vaccines against A. nosocomialis infection.


Subject(s)
Acinetobacter/pathogenicity , Bacterial Outer Membrane Proteins/metabolism , Cell Survival , Virulence Factors/metabolism , A549 Cells , Acinetobacter/genetics , Bacterial Outer Membrane Proteins/genetics , Bacterial Outer Membrane Proteins/isolation & purification , Biofilms/growth & development , Cell Line , Gene Deletion , Genetic Complementation Test , Humans , Mutation , Virulence , Virulence Factors/genetics , Virulence Factors/isolation & purification
12.
Infect Genet Evol ; 36: 1-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26341860

ABSTRACT

This study investigated the genetic basis of antimicrobial resistance and the epidemiological characteristics of 125 carbapenem-resistant Acinetobacter baumannii (CRAB) isolates collected from 2011 to 2012 in a Korean hospital. All CRAB isolates showed an extensively drug-resistant phenotype, but were susceptible to tigecycline. The blaOXA-23 and armA genes were mainly responsible for resistance to carbapenems and aminoglycosides, respectively. Four colistin-resistant CRAB isolates with different pulsotypes were identified. All four colistin-resistant isolates had a deletion at nucleotide 776 in lpxA, while one also had an insertion at nucleotide 732 in lpxA. All CRAB isolates belonged to three sequence types (STs): ST191 (n=118), ST208 (n=6), and ST436 (n=1), but were classified into 33 arbitrary pulsotypes. Of the CRAB ST191 isolates, two main arbitrary pulsotypes 5 (n=20) and 18 (n=17) emerged sequentially, but were not clonally related to CRAB isolates collected from 2009 to 2010 in the same hospital. Furthermore, of the two main pulsotypes identified among CRAB ST191 isolates from 2009 to 2010, one was clonally related to sporadic CRAB ST191 isolates from 2011 to 2012, but the other was not related to any CRAB isolate from 2011 to 2012. In conclusion, this study shows the clonal dynamics of CRAB ST191 isolates in a Korean hospital during the last four years.


Subject(s)
Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Carbapenems/pharmacology , Cross Infection , Genotype , beta-Lactam Resistance/genetics , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter baumannii/classification , Acinetobacter baumannii/isolation & purification , Acyltransferases/genetics , Cluster Analysis , Hospitals , Humans , Microbial Sensitivity Tests , Molecular Typing , Mutation , Phenotype , Republic of Korea , beta-Lactamases/genetics
13.
PLoS One ; 8(8): e71751, 2013.
Article in English | MEDLINE | ID: mdl-23977136

ABSTRACT

Acinetobacter baumannii is increasingly becoming a major nosocomial pathogen. This opportunistic pathogen secretes outer membrane vesicles (OMVs) that interact with host cells. The aim of this study was to investigate the ability of A. baumannii OMVs to elicit a pro-inflammatory response in vitro and the immunopathology in response to A. baumannii OMVs in vivo. OMVs derived from A. baumannii ATCC 19606(T) induced expression of pro-inflammatory cytokine genes, interleukin (IL)-1ß and IL-6, and chemokine genes, IL-8, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1, in epithelial cells in a dose-dependent manner. Disintegration of OMV membrane with ethylenediaminetetraacetic acid resulted in low expression of pro-inflammatory cytokine genes, as compared with the response to intact OMVs. In addition, proteinase K-treated A. baumannii OMVs did not induce significant increase in expression of pro-inflammatory cytokine genes above the basal level, suggesting that the surface-exposed membrane proteins in intact OMVs are responsible for pro-inflammatory response. Early inflammatory processes, such as vacuolization and detachment of epithelial cells and neutrophilic infiltration, were clearly observed in lungs of mice injected with A. baumannii OMVs. Our data demonstrate that OMVs produced by A. baumannii elicit a potent innate immune response, which may contribute to immunopathology of the infected host.


Subject(s)
Acinetobacter baumannii/immunology , Bacterial Outer Membrane Proteins/immunology , Immunity, Innate/immunology , Secretory Vesicles/immunology , Acinetobacter baumannii/drug effects , Animals , Cell Line , Cell Membrane/drug effects , Cell Membrane/metabolism , Cytokines/metabolism , Edetic Acid/pharmacology , Endopeptidase K/pharmacology , Epithelial Cells/drug effects , Epithelial Cells/immunology , Epithelial Cells/microbiology , Epithelial Cells/pathology , Female , Humans , Immunity, Innate/drug effects , Inflammation/pathology , Mice , Mice, Inbred BALB C , Mutation/genetics , Secretory Vesicles/drug effects
14.
Infect Genet Evol ; 19: 219-22, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23886617

ABSTRACT

Emergence and spread of specific carbapenem-resistant Acinetobacter baumannii (CRAB) clones cause a serious therapeutic problem. This study was aimed to investigate the clonal diversity and genetic basis of antimicrobial resistance among the 69 CRAB isolates from 2009 to 2010 in a Korean hospital. All CRAB isolates were found to be sequence type (ST) 2 using the Institute Pasteur's multilocus sequence typing (MLST) scheme, but classified into two sequence groups and nine pulsotypes. Fifty-six CRAB isolates belonging to two main pulsotypes were found to be ST191 using the Bartual's MLST scheme. All CRAB isolates showed an extensively drug-resistant phenotype. The blaOXA-51/blaOXA-23, blaAmpC/blaPER-1 and armA genes were largely responsible for resistance to carbapenems, extended-spectrum ß-lactams and aminoglycosides, respectively. The first CRAB strains identified in 2005 in this hospital were found to be ST2 using the Institute Pasteur's MLST scheme, but showed ST353 using the Bartual's MLST scheme and different pulsotypes from the CRAB isolates from 2009 to 2010. In conclusion, this is the first report of emergence and spread of A. baumannii ST191 in Korea, as well of the genetic basis of its antimicrobial resistance.


Subject(s)
Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Carbapenems/pharmacology , Cross Infection/microbiology , Drug Resistance, Multiple, Bacterial , Anti-Bacterial Agents/pharmacology , Cluster Analysis , DNA, Bacterial/analysis , DNA, Bacterial/genetics , Hospitals, University , Humans , Republic of Korea , beta-Lactam Resistance
15.
J Microbiol ; 50(1): 175-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22367955

ABSTRACT

In this study, we examined the biofilm forming ability, the mRNA expression of curli genes and the morphologies of curli fimbriae and biofilms in clinical isolates of Enterobacter cloacae. The csgBA operon was found in 11 (78.6%) of the 14 isolates. The ability of E. cloacae isolates to form biofilms was significantly correlated with the mRNA expression level of the csgA and csgD genes. The curli protein fimbriae appeared as tangled fibers and the curli-proficient strain formed mature biofilms. Our data suggest that the expression of the curli fimbriae play an important role in biofilm formation in E. cloacae.


Subject(s)
Bacterial Adhesion , Bacterial Proteins/metabolism , Biofilms/growth & development , Enterobacter cloacae/physiology , Fimbriae, Bacterial/physiology , Bacterial Proteins/genetics , Enterobacter cloacae/growth & development , Gene Expression Profiling , Humans , RNA, Messenger/biosynthesis , RNA, Messenger/genetics
16.
PLoS One ; 6(11): e27958, 2011.
Article in English | MEDLINE | ID: mdl-22114730

ABSTRACT

Gram-negative bacteria produce outer membrane vesicles that play a role in the delivery of virulence factors to host cells. However, little is known about the membrane-derived vesicles (MVs) produced by gram-positive bacteria. The present study examined the production of MVs from Staphylococcus aureus and investigated the delivery of MVs to host cells and subsequent cytotoxicity. Four S. aureus strains tested, two type strains and two clinical isolates, produced spherical nanovesicles during in vitro culture. MVs were also produced during in vivo infection of a clinical S. aureus isolate in a mouse pneumonia model. Proteomic analysis showed that 143 different proteins were identified in the S. aureus-derived MVs. S. aureus MVs were interacted with the plasma membrane of host cells via a cholesterol-rich membrane microdomain and then delivered their component protein A to host cells within 30 min. Intact S. aureus MVs induced apoptosis of HEp-2 cells in a dose-dependent manner, whereas lysed MVs neither delivered their component into the cytosol of host cells nor induced cytotoxicity. In conclusion, this study is the first report that S. aureus MVs are an important vehicle for delivery of bacterial effector molecules to host cells.


Subject(s)
Bacterial Proteins/analysis , Cytoplasmic Vesicles/metabolism , Laryngeal Neoplasms/pathology , Neutropenia/pathology , Proteomics , Staphylococcal Infections/metabolism , Staphylococcal Infections/pathology , Animals , Blotting, Western , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/microbiology , Carcinoma, Squamous Cell/pathology , Cell Death , Female , Flow Cytometry , Humans , Laryngeal Neoplasms/metabolism , Laryngeal Neoplasms/microbiology , Lung/microbiology , Mice , Mice, Inbred C57BL , Neutropenia/metabolism , Neutropenia/microbiology , Pneumonia/metabolism , Pneumonia/microbiology , Pneumonia/pathology , Protein Transport , Staphylococcus aureus/physiology , Virulence Factors
17.
18.
Int J Antimicrob Agents ; 35(1): 76-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19781915

ABSTRACT

Mutations in DNA gyrase and topoisomerase IV genes are the main mechanisms of resistance to quinolones. In this study, we determined mutations in gyrA, gyrB, parC and parE among 57 ciprofloxacin-resistant Escherichia coli isolates from a South Korean hospital and analysed the relationship between the minimal inhibitory concentrations (MICs) of fluoroquinolones and mutations in the topoisomerase IV gene. All ciprofloxacin-resistant E. coli isolates carried double mutations in gyrA and at least a single mutation in parC; some isolates also carried a single mutation in parE. The most common mutations were S83L and D87N in gyrA, S80I in parC and S458A in parE, which accounted for 25% of isolates. Single mutations in parE at L445I, S458P and S458W were identified for the first time. Double mutations in parC and a combination of single mutations in parC and parE significantly increased the MIC values of fluoroquinolones. In vitro induction of resistance to ciprofloxacin showed that double mutations in gyrA were a prerequisite to conferring a resistant phenotype to fluoroquinolones, and an additional mutation in the topoisomerase IV gene increased the MIC values of ciprofloxacin. In conclusion, emergence of a new mutation in parC and parE and its accumulation induces high levels of resistance to fluoroquinolones in E. coli.


Subject(s)
Anti-Bacterial Agents/pharmacology , DNA Topoisomerase IV/genetics , Drug Resistance, Bacterial , Escherichia coli Proteins/genetics , Escherichia coli/drug effects , Fluoroquinolones/pharmacology , Mutation, Missense , Amino Acid Substitution/genetics , Ciprofloxacin/pharmacology , DNA Gyrase/genetics , Humans , Microbial Sensitivity Tests , Point Mutation , Republic of Korea
19.
Korean J Med Educ ; 22(2): 101-11, 2010 Jun.
Article in English | MEDLINE | ID: mdl-25813809

ABSTRACT

PURPOSE: The purpose of this study is to survey the awareness of faculty (F) and students (S) on 'good teaching' and to analyze an example of good lesson, finally to identify the requirements of 'good teaching' in medical education. METHODS: Quantitative and qualitative methods were applied simultaneously. First, survey using a questionnaire was analyzed by frequency analysis and verified using chi-square-test, Mann-Whitney test. Second, the case of good teaching and qualitative data were analyzed by 'priori codes coding' and 'open coding'. RESULTS: The results of survey are as follows: Both faculty and students regarded lessons that taught important content easy to understand (F: 50%; S: 69.1%); Lessons that allow students make sure important information (F: 48.6%; S: 51.4%); Lessons that prepare and plan considering the student's level and interest (F: m=3.78; S: m=3.76) were good lessons. Faculty wanted lessons that improve student's academic achievement (35.7%), while students choose lessons that deliver curriculum effectively using appropriate teaching method (47.1%). According to the results of case analysis, it turned out that characteristics of good teaching were as follows: Thorough plan and preparation of content, various teaching methods and materials, encouragement of intellectual inquiry and curiosity, active interaction between faculty and students, clear feedback and reasonable evaluation. CONCLUSION: Requirements of good teaching are open to faculty at school of medicine and are to be utilized as guidelines to monitor and improve their instruction.

20.
FEMS Microbiol Lett ; 301(2): 224-31, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19878322

ABSTRACT

Bacteremia is a common systemic disease caused by Acinetobacter baumannii, an important hospital-acquired pathogen among critically ill patients. The complement system is central to innate immune defense against invading bacteria in the blood. The present study investigated the susceptibility of clinical A. baumannii isolates to normal human sera (NHS), and determined the resistance mechanism of A. baumannii against complement-mediated lysis. The survival of A. baumannii isolates from bacteremic patients was significantly decreased in undiluted NHS, but they were resistant to 40% NHS. The alternative complement pathway was responsible for the direct killing of bacteria. The main regulator of the alternative complement pathway, factor H, bound to the surface of live A. baumannii treated with NHS. Factor H interacted with the outer membrane proteins with molecular sizes of 38 (AbOmpA), 32, and 24 kDa. The isogenic AbOmpA(-) mutant was highly susceptible to NHS in comparison with the wild-type A. baumannii strain, suggesting that AbOmpA was an important complement regulator-acquiring surface protein. These results indicate that A. baumannii evades complement attack through the acquisition of factor H to their surface.


Subject(s)
Acinetobacter baumannii/immunology , Bacterial Outer Membrane Proteins/metabolism , Blood Bactericidal Activity , Complement Factor H/metabolism , Acinetobacter Infections/immunology , Acinetobacter Infections/microbiology , Acinetobacter baumannii/isolation & purification , Bacteremia/immunology , Bacteremia/microbiology , Bacterial Outer Membrane Proteins/chemistry , Bacterial Outer Membrane Proteins/genetics , Critical Illness , Gene Knockout Techniques , Humans , Microbial Viability , Molecular Weight , Protein Binding
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