Genome-wide association study identifies TNFSF15 associated with childhood asthma.

BACKGROUND: Genome-wide association studies (GWASs) of asthma have identified several risk alleles and loci, but most have been conducted in individuals with European-ancestry. Studies in Asians, especially children, are still lacking. We aimed to identify susceptibility loci by performing the first GWAS of asthma in Korean children with persistent asthma. METHODS: We used a discovery set of 741 children with persistent asthma as cases and 589 healthy children and 551 healthy adults as controls to perform a GWAS. We validated our GWAS findings using UK Biobank data. We then used the Genotype-Tissue Expression database to identify expression quantitative trait loci of candidate variants. Finally, we quantified proteins of genes associated with asthma. RESULTS: Variants at the 17q12-21 locus and SNPs in CYBRD1 and TNFSF15 genes were associated with persistent childhood asthma at genome-wide thresholds of significance. Four SNPs in the TNFSF15 gene were also associated with childhood-onset asthma in British white participants in the UK Biobank data. The asthma-associated rs7856856-C allele, the lead SNP, was associated with decreased TNFSF15 expression in whole blood and in arteries. Korean children with asthma had lower serum TNFSF15 levels than controls, and those with the asthma risk rs7856856-CC genotype exhibited the lowest serum TNFSF15 levels overall, especially asthmatic children. CONCLUSIONS: Our GWAS of persistent childhood asthma with allergic sensitization identified a new susceptibility gene, TNFSF15, and replicated associations at the 17q12-21 childhood-onset asthma locus. This novel association may be mediated by reduced expression of serum TNFSF15 and loss of suppression of angiogenesis.

The association of plasma cytokines including VEGF with recurrent wheezing in allergic patients.

BACKGROUND: Various cytokines have been studied to determine their functions in the pathogenesis of allergic diseases and their potential as therapeutic targets, but the roles and clinical applicability of many of these cytokines still remain unclear. OBJECTIVE: We aimed to measure the plasma levels of eight cytokines known to be relevant to allergic diseases, and to determine their association with the diagnostic characteristics of allergic patients. METHODS: The levels of a panel of eight cytokines (IL-5, IL-10, IL12p70, Leptin, CXCL5/ENA-78, CCL2/MCP-1, PDGFBB, and VEGF) were measured in plasma obtained from 83 allergic patients. We investigated whether the cytokine levels differed between children and adults. Statistical analyses were then performed to examine their association with the diagnostic characteristics of allergic patients. RESULTS: The levels of leptin, CCL2/MCP-1, PDGFBB, and VEGF were significantly higher in adult patients with allergic rhinitis than in children. Among patients with asthma, the levels of leptin and PDGFBB were elevated in adults. PDGFBB and VEGF levels were significantly associated with asthma. Interestingly, there was a significant association between VEGF level and recurrent wheezing regardless of the analyzed conditions. The levels of VEGF and PDGFBB or CCL2/MCP-1 showed a significant increase together in the presence of recurrent wheezing in child patients. CONCLUSIONS: The plasma levels of four cytokines, particularly VEGF, showed significant associations with some diagnostic characteristics in allergic patients. We suggested that plasma VEGF, which performs pleiotropic functions in allergic responses, could serve as a serological marker relevant to recurrent wheezing in allergic patients.

Association between sensitization and allergic diseases in 7-years-old Korean children.

BACKGROUND: Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children. OBJECTIVE: We characterized the association between sensitization patterns and allergic diseases. METHODS: A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. RESULTS: The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. CONCLUSIONS: The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Vegetable dietary pattern may protect mild and persistent allergic rhinitis phenotype depending on genetic risk in school children.

BACKGROUND: The effect of diet on allergic rhinitis (AR), its severity in children, and whether it modifies AR depending on genetic susceptibility are unknown. We investigated the association between dietary patterns and AR in school children and the influence of diet on AR according to a genetic risk score (GRS). METHODS: Totally, 435 7-year-old school children were recruited from the Panel Study on Korean Children. We used dietary patterns (vegetable, sugar, and meat) and dietary inflammatory index (DII) as dietary parameters. AR and its severity were defined by questionnaires about treatment in the previous 12 months and the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, respectively. A GRS was calculated using 6 single nucleotide polymorphisms for allergic diseases. RESULTS: A vegetable diet containing a lot of anti-inflammatory nutrients and higher vitamin D level in blood were negatively correlated, while DII was positively correlated with triglyceride level and triglyceride/HDL cholesterol. Vegetable diet (aOR, 95% CI = 0.73, 0.58-0.94) and DII (1.13, 1.01-1.28) were associated with AR risk. In particular, a high-vegetable diet resulted in a lower risk of mild and persistent AR (aOR, 95% CI = 0.24, 0.10-0.56) while a high DII represented a higher risk (2.33, 1.06-5.10). The protective effect of vegetable diet on AR appeared only among children with a lower GRS (adjusted P = .018). CONCLUSIONS: A vegetable dietary pattern characterized by high intake of anti-inflammatory nutrients and higher vitamin D level in blood might be associated with a lower risk of mild and persistent AR. This beneficial effect is modified by a genetic factor.

Asthma control test reflects not only lung function but also airway inflammation in children with stable asthma.

Objective: Various numerical asthma control tools have been developed to distinguish different levels of symptom control. We aimed to examine whether the asthma control test (ACT) is reflective of objective findings such as lung function, fractional exhaled nitric oxide (FeNO) and laboratory data in patients with stable asthma.Methods: We included patients who were enrolled in the Korean Childhood Asthma Study. ACT, spirometry, blood tests and FeNO were performed in patients after stabilization of their asthma. We examined differences among spirometry parameters, blood tests and FeNO according to control status as determined by ACT and investigated for any significant correlations.Results: The study population consisted of 441 subjects. Spirometry showed that forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity and FEV1/forced vital capacity were all significantly higher in the controlled asthma group. Likewise, FeNO and percent-change in FEV1 were both significantly lower in the controlled asthma group. In blood tests, the eosinophil fraction was significantly lower in the controlled asthma group while white blood cell count was significantly higher in the controlled asthma group. Lastly, among the various factors analyzed, only provocative concentration of methacholine causing a 20% fall in FEV1 significantly correlated with ACT score.Conclusion: ACT is useful as part of the routine evaluation of asthmatic children and should be used as a complement to existing tools such as spirometry and FeNO measurement.

Korean childhood asthma study (KAS): a prospective, observational cohort of Korean asthmatic children.

BACKGROUND: Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. METHODS: We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects' baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. DISCUSSION: Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects' personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

Prenatal maternal distress affects atopic dermatitis in offspring mediated by oxidative stress.

BACKGROUND: Recent evidence suggests that prenatal maternal distress increases the risk of allergic diseases in offspring. However, the effect of prenatal maternal depression and anxiety on atopic dermatitis (AD) risk remains poorly understood. OBJECTIVE: We investigated whether prenatal maternal distress is associated with AD risk in offspring and whether the mechanism is mediated by reactive oxygen species. METHODS: Two general population-based birth cohorts formed the study. One cohort (Cohort for Childhood Origin of Asthma and Allergic Diseases [COCOA]) consisted of 973 mother-baby dyads, and the other (Panel Study on Korean Children [PSKC]) consisted of 1531 mother-baby dyads. The association between prenatal distress and AD was assessed by using Cox proportional hazards and logistic regression models. In COCOA placental 11ß-hydroxysteroid dehydrogenase type 2 and glutathione levels and serum IgE levels in 1-year-old children were measured. RESULTS: In COCOA and PSKC AD occurred in 30.6% (lifetime prevalence) and 11.6% (1 year prevalence) of offspring, respectively. Prenatal maternal distress increased the risk of AD in offspring, both in COCOA (hazard ratio for depression, 1.31 [95% CI, 1.02-1.69]; hazard ratio for anxiety, 1.41 [95% CI, 1.06-1.89]) and PSKC (odds ratio for distress, 1.85 [95% CI, 1.06-3.25]). In COCOA both prenatal maternal depression and anxiety scores were positively related to the predicted probability of AD (P < .001 in both). Prenatal distress decreased placental glutathione to glutathione disulfide ratios (P = .037) and, especially in those who later had AD, decreased placental 11ß-hydroxysteroid dehydrogenase type 2 levels (P = .010) and increased IgE levels at 1 year of age (P = .005). CONCLUSION: Prenatal maternal depression and anxiety promote risk of AD in offspring. Maternal distress increases the predicted probability of AD. The mechanism might involve chronic stress, abnormal steroid levels, and reactive oxygen species.

Comparative study of lung toxicity of E-cigarette ingredients to investigate E-cigarette or vaping product associated lung injury.

No comparative study has yet been performed on the respiratory effects of individual E-cigarette ingredients. Here, lung toxicity of individual ingredients of E-cigarette products containing nicotine or tetrahydrocannabinol was investigated. Mice were intratracheally administered propylene glycol (PG), vegetable glycerin (VG), vitamin E acetate (VEA), or nicotine individually for two weeks. Cytological and histological changes were noticed in PG- and VEA-treated mice that exhibited pathophysiological changes which were associated with symptoms seen in patients with symptoms of E-cigarette or Vaping Use-Associated Lung Injuries (EVALI) or E-cigarette users. Compared to potential human exposure situations, while the VEA exposure condition was similar to the dose equivalent of VEA content in E-cigarettes, the PG condition was about 47-137 times higher than the dose equivalent of the daily PG intake of E-cigarette users. These results reveal that VEA exposure is much more likely to cause problems related to EVALI in humans than PG. Transcriptomic analysis revealed that PG exposure was associated with fibrotic lung injury via the AKT signaling pathway and M2 macrophage polarization, and VEA exposure was associated with asthmatic airway inflammation via the mitogen-activated protein kinase signaling pathway. This study provides novel insights into the pathophysiological effects of individual ingredients of E-cigarettes.

Association of heat shock protein 8 with atopic march in a murine experimental model.

Background: Atopic march (AM), a unique characteristic of allergic diseases, refers to the sequential progression of atopic dermatitis (AD) in infants to allergic asthma and allergic rhinitis in children and young adults, respectively. Although there are several studies on AM, the establishment of an AM murine model to expand our understanding of the underlying mechanism and to identify the potential biomarkers is yet to be achieved. In this study, an improved murine model was established by applying a method to minimize skin irritation in inducing AD, and it was used to perform integrated analyses to discover candidate biomarkers. Methods: To induce atopic dermatitis, 2,4-dinitrochlorobenzene (DNCB) was applied to the ear skin once a week, and this was continued for 5 weeks. From the second application of DNCB, Dermatophagoides pteronyssinus (Dp) extract was applied topically 2 days after each DNCB application; this was continued for 4 weeks. Dp sensitization and intranasal challenges were then performed for 4 weeks to develop conditions mimicking AM. Results: Exacerbated airway inflammation and allergic responses observed in the AM-induced group suggested successful AM development in our model. Two-dimensional gel electrophoresis (2-DE) and mass spectrometry analysis identified 753 candidate proteins from 124 2-DE spots differentially expressed among the experimental groups. Functional analyses, such as Gene Ontology (GO) annotation and protein-protein interaction (PPI) analysis were conducted to investigate the relationship among the candidate proteins. Seventy-two GO terms were significant between the two groups; heat shock protein 8 (Hspa8) was found to be included in six of the top 10 GO terms. Hspa8 scored high on the PPI parameters as well. Conclusion: We established an improved murine model for AM and proposed Hspa8 as a candidate biomarker for AM.

Alterations of lung microbial communities in obese allergic asthma and metabolic potential.

In recent years, there has been a rapid increase in microbiome studies to explore microbial alterations causing disease status and unveil disease pathogenesis derived from microbiome environmental modifications. Convincing evidence of lung microbial changes involving asthma has been collected; however, whether lung microbial changes under obesity leads to severe asthma in a state of allergen exposure has not been studied sufficiently. Here, we measured bacterial alterations in the lung of an allergen mouse model induced by a high fat diet (HFD) by using 16S rRNA gene sequencing. A total of 33 pathogen­free 3­week­old male C57BL/6 mice were used, and they divided randomly into two groups. The Chow diet (n = 16) and high fat diet (n = 17) was administrated for 70 days. Mice were sensitized with PBS or Dermatophagoides pteronyssinus extract (Der.p), and concentration levels of total IgE and Der.p-IgE in the blood were measured to quantify immune responses. Although there were no meaningful differences in bacterial species richness in the HFD mouse group, momentous changes of bacterial diversity in the HFD mouse group were identified after the mouse group was exposed to allergens. At a genus level, the fluctuations of taxonomic relative abundances in several bacteria such as Ralstonia, Lactobacillus, Bradyrhizobium, Gaiella, PAC001932_g, Pseudolabrys, and Staphylococcus were conspicuously observed in the HFD mouse group exposed to allergens. Also, we predicted metabolic signatures occurring under microbial alterations in the Chow group versus the Chow group exposed to allergens, as well as in the HFD mouse group versus the HFD group exposed to allergens. We then compared their similarities and differences. Metabolic functions associated with macrophages such as propanoate metabolism, butanoate metabolism, and glycine-serine-threonine metabolism were identified in the HFD group versus the Chow group. These results provide new insights into the understanding of a microbiome community of obese allergic asthma, and shed light on the functional roles of lung microbiota inducing the pathogenesis of severe asthma.

A multicenter anaphylaxis registry in Korea: Clinical characteristics and acute treatment details from infants to older adults.

BACKGROUND: Although the prevalence of anaphylaxis is increasing worldwide, the large-scale studies in Asia evaluating anaphylaxis in all age groups are limited. We aimed to collect more precise and standardized data on anaphylaxis in Korea using the first multicenter web-based registry. METHODS: Twenty-two departments from 16 hospitals participated from November 2016 to December 2018. A web-based case report form, designed by allergy specialists, was used to collect anaphylaxis data. RESULTS: Within the 2-year period, 558 anaphylaxis cases were registered. The age of registered patients ranged from 2 months to 84 years, and 60% were aged <18 years. In children and adolescents, foods (84.8%) were the most common cause of anaphylaxis, followed by drugs (7.2%); in adults, drugs (58.3%) were the most common cause, followed by foods (28.3%) and insect venom (8.1%). The onset time was ≤10 min in 37.6% of patients. Among the 351 cases registered via the emergency department (ED) of participating hospitals, epinephrine was administered to 63.8% of patients. Among those receiving epinephrine in the ED, 13.8% required 2 or more epinephrine shots. Severe anaphylaxis accounted for 23.5% cases (38.1% in adults; 13.7% in children); patients with drug and insect venom-induced anaphylaxis had higher rates of severe anaphylaxis. CONCLUSION: This multicenter registry provides data on anaphylaxis for all age groups for the first time in Asia. The major causes and severity of anaphylaxis were remarkably different according to age group, and the acute treatment features of anaphylaxis in the EDs were examined in detail.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification.

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77-15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40-40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Investigation of beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa isolated from non-tertiary care hospitals in Korea.

A total of 2,280 nonduplicate clinical isolates of Pseudomonas aeruginosa, obtained nationwide from Korean non-tertiary care hospitals from 2002 to 2005, were identified and their susceptibilities to aminoglycosides, antipseudomonal penicillins, carbapenems, cephalosporins, monobactams, and quinolones were studied, together with their production of beta- lactamases. Using disk diffusion and minimum inhibitory concentration tests, it was found that 2.9% of isolates were multidrug-resistant (MDR) P. aeruginosa. An EDTA-disk synergy test, PCR amplification with specifically designed primers, and direct sequencing of the PCR products showed that the blaOXA-10, blaVIM-2, blaOXA-2, blaOXA-17, blaPER-1, blaSHV-12, and blaIMP-1 genes were carried by 34.3%, 26.9%, 3.0%, 3.0%, 1.5%, 1.5%, and 1.5% of 67 MDR P. aeruginosa isolates, respectively. The prevalence of MDR P. aeruginosa was three-fold higher, compared with that from the United States. More than two types of beta-lactamase genes were carried by 10.4% of isolates. The most prevalent beta-lactamase genes were blaVIM-2 and blaOXA-10. This study is the first description of MDR P. aeruginosa from non-tertiary care hospitals in Korea and the coexistence of the blaOXA-10 gene with blaVIM-2, blaIMP-1, or blaPER-1 in these clinical isolates.

Prevalence of Self-reported Allergic Diseases and IgE Levels: A 2010 KNHANES Analysis.

PURPOSE: The prevalence of allergic diseases is known to be associated with both demographic and environmental factors. Herein, we aimed to determine significant factors associated with the prevalence of allergic diseases and with total immunoglobulin E (tIgE) and specific immunoglobulin E (sIgE) levels in Korea. METHODS: We analyzed unweighted data collected by the 2010 Korea National Health and Nutrition Examination Survey for 2,342 subjects who underwent serum tests for tIgE and sIgE to Dermatophagoides farinae, dog, and Blattella germanica, representing a sample of 16,003,645 citizens, by considering the sample weight and stratification. RESULTS: The overall prevalence of self-reported allergic diseases was 37.6%. The prevalence rates of allergic rhinitis and atopic dermatitis decreased with age, whereas the asthma prevalence was not affected by the age of the subjects. When analyzed according to the type of allergic diseases, the prevalence of self-reported allergic disease was significantly associated with various factors (e.g. age, occupation, living in urban areas, and depression). The tIgE level decreased with age, but later increased. Elevation of tIgE was significantly associated with male sex, type of occupation, obesity, and smoking status. However, the risk factors for the increased sIgE levels to each allergen were quite different. Sensitization to D. farinae was more likely in young subjects, whereas the prevalence of sensitization to B. germanica was significantly higher in subjects with male sex, residing in a house (houses), and with glucose intolerance. Finally, young age and the smoking status were significantly associated with sensitization to dog. CONCLUSIONS: Various demographic and environmental factors were significantly associated with the prevalence of self-reported allergic diseases and the levels of tIgE and sIgE to D. farinae, B. germanica, and dog in Korea.

Interaction between 25-hydroxyvitamin D and variants at 17q12-21 on respiratory infections.

OBJECTIVES: 25-hydroxyvitamin D (25[OH]D) deficiency and genetic variants at the 17q12-21 locus are independent risk factors for respiratory tract infections (RTIs). We aimed to investigate whether the effect of 25(OH)D at birth and 1 year of age and the polymorphism at the 17q12-21 locus, or interactions between these two factors, increase susceptibility to RTIs in the first year of life. METHODS: We tested cord-blood (CB) 25(OH)D at birth and 1 year of age and genotypes of a variant at the 17q12-21 locus for associations with RTIs, particularly lower respiratory tract infections (LRTIs), and determined whether there exist interactions between 25(OH)D and 17q12-21 genotypes in a birth cohort of 473 infants. RESULTS: The levels of CB 25(OH)D inversely associate with development of RTIs and LRTIs during the first year of life. There exists an inverse association of 25(OH)D at birth, but not at 1 year, with the risk of acquiring LRTIs in early infancy (adjusted odds ratio [aOR], 2.37; 95% confidence interval [CI]: 1.23-4.60; P = 0.010 and aOR, 0.50; 95%CI: 0.23-1.12; P = 0.094). We have also found a significant interaction between CB 25(OH)D and a variant at the 17q12-21 locus with respect to the development of early LRTIs, such that associations between a variant at the 17q12-21 locus and LRTIs are restricted to infants with low CB 25(OH)D concentrations (P for interaction = 0.013). In addition, when infants with a variant at the 17q12-21 locus had been exposed to chronic 25(OH)D deficiency over the first year, their risk of LRTIs was increased. CONCLUSION: CB 25(OH)D deficiency during fetal life contribute to the development of LRTIs in genetically susceptible infants. Pediatr Pulmonol. 2016; 51:958-967. © 2016 Wiley Periodicals, Inc.

Alterations in the GyrA and GyrB subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa.

The presence of fluoroquinolone resistance-associated alterations in topoisomerase II and IV were investigated for 103 nfxC-like type Pseudomonas aeruginosa isolates. The most nfxC-like type isolates (98.1%) possessed the substitution of Ile for Thr-83 in GyrA. A single alteration in GyrA (Thr-83-->Ile) was the most frequently detected and the next common alteration was two alterations with Thr-83-->Ile in GyrA and Ser-87-->Leu in ParC. A novel alteration at position Glin-106 of GyrA, which was suggested to be responsible for fluoroquinolone resistance, was identified. Our study revealed that the alterations in GyrB (Glu-468-->Asp) and in ParE (Asp-419-->Asn or Glu-459-->Asp) play a complementary role in the acquisition of resistance to fluoroquinolone. There was a correlation between the ciprofloxacin MIC and the number of resistance-associated alterations in GyrA, GyrB, ParC and ParE of P. aeruginosa isolates.

Clonal dissemination and mupA gene polymorphism of mupirocin-resistant Staphylococcus aureus isolates from long-term-care facilities in South Korea.

We identified 25 high-level mupirocin-resistant (MuH) and 21 low-level mupirocin-resistant (MuL) Staphylococcus aureus isolates from eight long-term-care facilities (LTCFs). The pulsed-field gel electrophoresis patterns of 19 MuH and 19 MuL isolates from two facilities were identical for 18 and 15 isolates, respectively. The most predominant mupA restriction fragment length polymorphism type was found in 21 MuH isolates. We conclude that clonal transmission of MuH and MuL S. aureus strains occurred in these LTCFs. This is the first report of clonal transfer of mupirocin resistance in LTCFs.

Mutations in the gyrA and parC genes in ciprofloxacin-resistant clinical isolates of Acinetobacter baumannii in Korea.

Mutation with Ser-83-->Leu in gyrA gene was associated with the principal mutation for ciprofloxacin resistance in clinical isolates of Acinetobacter baumannii. Double mutation, Ser-83-->Leu in gyrA gene and Ser-80-->Leu in parC gene, was the most frequently detected among ciprofloxacin-resistant isolates. A novel mutation with Ser-80-->Trp in parC gene, in addition to mutation in gyrA gene, was associated with a high-level ciprofloxacin resistance. These results suggested that the presence of an additional mutation in the parC gene contributed to a higher-level of ciprofloxacin resistance than a single mutation in the gyrA gene (geometric mean MICs of ciprofloxacin, 44.1 versus 16 microg/ml, P < 0.05).