Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.
Anti-Bacterial Agents/administration & dosage* ; Bone and Bones/metabolism* ; Cellular Microenvironment ; Humans ; Immune System/immunology* ; Lymphocyte Subsets/immunology* ; Osteitis/microbiology* ; Osteoblasts/physiology* ; Osteoclasts/physiology* ; Staphylococcal Infections

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) are important pathogens causing nosocomial infections in Korean hospitals. This study aimed to investigate the epidemiological and genetic diversity of clinical S. aureus isolates in healthcare settings from 2001 to 2008. METHODS: Samples and data were obtained from 986 individuals as part of the National Antimicrobial Surveillance Project, involving 10 regions nationwide. Molecular typing studies, including multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing were performed, and a representative clone of Korean MRSA was classified by combinational grouping using a DiversiLab (DL; bioMérieux, France) repetitive element polymerase chain reaction (rep-PCR) system. RESULTS: Nine Korean MRSA clones (KMRSA-1 to -9) were identified by analysis of genetic backgrounds and molecular characteristics. KMRSA-1 to -3, expressing clonal complex (CC) 5 (carrying SCCmec II), CC8 (carrying SCCmec III), and CC72 (carrying SCCmec IV) were spread nationwide. In contrast, KMRSA-6 was highly prevalent in Gyeongsangnam-do, and KMRSA-4 was highly prevalent in Jeollanam-do and Jeollabuk-do. CONCLUSIONS: Epidemic KMRSA clones were genetically similar to major clones identified from the USA, with the exception of KMRSA-2, which had the SCCmec III type. Our results provide important insights into the distribution and molecular genetics of MRSA strains in Korea and may aid in the monitoring of MRSA spread throughout the country.
Bacterial Proteins/genetics ; DNA, Bacterial/genetics/metabolism ; Electrophoresis, Gel, Pulsed-Field ; Hospitals ; Humans ; Methicillin-Resistant Staphylococcus aureus/*genetics/isolation & purification ; Multilocus Sequence Typing ; Multiplex Polymerase Chain Reaction ; Prevalence ; Republic of Korea/epidemiology ; Staphylococcal Infections/diagnosis/*epidemiology/microbiology

OBJECTIVE: To investigate the influences of staphylococcus aureus in planktonic and biofilm forms on the expression of lysozyme, SLPI and gp340 in the human sinonasal explant model. METHOD: Mucosa samples from ethmoid sinus were collected from ten patients of cerebrospinal fluid leak and were cultured with and without S. aureus biofilms and planktonic cells. After the infection, the explant model was confirmed by CLSM, and the secretion of lysozyme, SLPI and gp340 was detected by enzyme-linked immunosorbent assay (ELISA) at 8, 16, and 24 h after S. aureus challenge. Expressions of lysozyme, SLPI and gp340 in mRNA and protein levels after 24 h S. aureus challenge were detected using RT-PCR, immunohistochemistry and Western bolt assay respectively. RESULT: The secretion of lysozyme, SLPI and gp340 in the explant model was observed with a trend to increase in a time-dependent manner. At 8 and 16 h after S. aureus challenge, the secretion of lysozyme, SLPI and gp340 in biofilms group was significantly higher than these in planktonic cells group and control group (P<0. 05). S. aureus biofilms enhanced the mRNA expressions of lysozyme, SLPI and gp340 significantly compared with planktonic cells and controls, and the mRNA expressions in the explant model challenged by planktonic cells were significantly higher than controls (P < 0.05). Although the Western bolt assay showed no differences between the lysozyme expression in the planktonic cells group and control group (P > 0.05), the biofilms enhanced the expressions of lysozyme, SLPI and gp340 significantly compared with planktonic cells and controls (P < 0.05). CONCLUSION S. aureus biofilm induced the expressions of lysozyme, SLPI and gp340 to a higher level than planktonic cells, indicating that S. aureus biofilm was an influencing factor on the innate immune system.
Biofilms ; Enzyme-Linked Immunosorbent Assay ; Ethmoid Sinus ; metabolism ; microbiology ; Humans ; Immunity, Innate ; Muramidase ; metabolism ; RNA, Messenger ; metabolism ; Receptors, Cell Surface ; metabolism ; Secretory Leukocyte Peptidase Inhibitor ; metabolism ; Staphylococcal Infections ; metabolism ; Tissue Culture Techniques

To compare immunological characteristics of Extracellular fibrinogen-binding protein (Efb) and Clumping factor A (CfA) of Staphylococcus aureus, we constructed two prokaryotic expression vector pET28a-Efb and pET28a-ClfA. After prokaryotical expression and purification, Efb and ClfA were used to immunize experimental animal. After the second immunization the antisera were collected and the antibody titers, the bacteria binding activity and adhesion inhibition activity of these antisera were detected by enzyme linked immunosorbent assay, adhesion inhibition assay and challenge. Both Efb and ClfA had Fibrinogen binding activity whereas the former had better Fibronectin binding activity. The bacteria binding capability of antisera of rabbits immunized with ClfA was better than that with Efb (P < 0.01). Both antisera of Efb and ClfA could inhibit adherence activity of Staphylococcus aureus to Fibrinogen and Fibronectin adherence compare to the control group (P < 0.01), and Efb had better adhesion inhibition activity than ClfA. The antibody titer of immunized group could reach 1:40 500. After the second immunization, both Efb and ClfA had good protective efficacy. This result constitutes a good foundation for Staphylococcus aureus subunit vaccine development.
Animals ; Antibodies, Bacterial ; blood ; Bacterial Adhesion ; Bacterial Proteins ; immunology ; Cattle ; microbiology ; Coagulase ; immunology ; Enzyme-Linked Immunosorbent Assay ; Fibrinogen ; metabolism ; Genetic Vectors ; Immune Sera ; immunology ; Immunization ; Rabbits ; Staphylococcal Infections ; immunology ; Staphylococcus aureus

BACKGROUND: Burn wounds lack normal barriers that protect against pathogenic bacteria, and burn patients are easily colonized and infected by Staphylococcus aureus. Toxic shock syndrome (TSS) is a rare but fatal disease caused by S. aureus. A lack of detectable antibodies to TSS toxin-1 (TSST-1) in serum indicates susceptibility to TSS. METHODS: A total of 207 patients (169 men and 38 women; median age, 42.5 yr) admitted to a burn center in Korea were enrolled in this study. The serum antibody titer to TSST-1 was measured by sandwich ELISA. S. aureus isolates from the patients' nasal swab culture were tested for TSST-1 toxin production by PCR-based detection of the TSST-1 toxin gene. RESULTS: One hundred seventy-four (84.1%) patients showed positive results for antibody against TSST-1. All patients aged > or =61 yr (n=28) and <26 months (n=7) were positive for the anti-TSST-1 antibody. S. aureus was isolated from 70 patients (33.8%), and 58.6% of the isolates were methicillin resistant. Seventeen patients were colonized with TSST-1-producing S. aureus. The antibody positivity in these 17 carriers was 88.2%, and the positivity in the non-carriers was 83.7%. CONCLUSIONS: Most burn patients had antibody to TSST-1, and nasal colonization with TSST-1-producing S. aureus was associated with positive titers of anti-TSST-1 antibody. Additionally, patients with negative titers of anti-TSST-1 antibody might be susceptible to TSS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Bacterial/*blood ; Bacterial Toxins/genetics/immunology/*metabolism ; Burns/blood/*immunology/*microbiology/pathology ; Child ; Child, Preschool ; Enterotoxins/genetics/immunology/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Male ; Middle Aged ; Nasal Cavity/microbiology ; Polymerase Chain Reaction ; Prevalence ; Staphylococcal Infections/epidemiology ; Staphylococcus aureus/isolation & purification/*metabolism ; Superantigens/genetics/immunology/*metabolism ; Young Adult

Coagulase-negative staphylococci (CoNS) are reported to be the leading cause of nosocomial bloodstream infections. Staphylococcus pettenkoferi is a novel member of CoNS that was first isolated from the human blood and bursitis wound in 2002. We have reported cases of 6 S. pettenkoferi strains isolated from blood specimens, including one pathogen and 5 contaminants and catheter colonizers. Brucker Biotyper (Brucker Daltonics, Bremen, Germany) and molecular typing with 16S rRNA gene sequencing confirmed the 6 isolates as S. pettenkoferi. The conventional phenotypic identification of these isolates is not reliable owing to their inconsistent biochemical characteristics. Five of the 6 isolates were found to be resistant to oxacillin, and all isolates showed susceptibility to vancomycin and linezolid. For accurate identification of this novel species, advanced methods by using Brucker Biotyper or molecular methods such as 16S rRNA gene sequencing are required.
Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology/therapeutic use ; DNA, Bacterial/chemistry/metabolism ; Drug Resistance, Bacterial/drug effects ; Female ; Humans ; Linezolid/pharmacology ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Oxacillin/pharmacology ; Phenotype ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Sequence Analysis, DNA ; Staphylococcal Infections/drug therapy/*microbiology/pathology ; Staphylococcus/drug effects/*genetics/isolation & purification ; Vancomycin/pharmacology

OBJECTIVETo investigate α-toxin-induced apoptosis of umbilical vein endothelial cells and explore its role in vertical infection of Staphylococcus aureus L-form.

METHODSHUV-EC-C cells exposed to different concentrations (0, 10, 30, 90, and 270 ng/ml) of α-toxin for different time lengths (0, 2, 4, 6, and 8 h) were examined for apoptosis using flow cytometry with Annexin V-PI staining. The levels of tumor necrosis factor-α (TNF-α) and the activities of, caspase-3 and caspase-8 in the cell culture were detected by ELISA and colorimetric method, respectively. α-Toxin-induced cell apoptosis was also analyzed in HUV-EC-C cells treated with a neutralizing antibody of TNF-α or with the inhibitory peptides of caspase-3 (zDEVD-FMK) and caspase-8 (zIETD-fmk).

RESULTSα-Toxin induced apoptosis of HUV-EC-C cells in a dose- and time-dependent manner and caused significantly enhanced expression of TNF-α and the activation of both caspase-3 and caspase-8. Inhibition of TNF-α with its neutralizing antibody and the inhibitory peptides of caspase-3 or -8 all significantly decreased α-toxin-induced cell apoptosis, and the caspase-3 inhibitor completely blocked α-toxin-induced cell apoptosis.

CONCLUSIONα-Toxin-induced apoptosis is partially mediated by the extrinsic cell death pathway of TNF-α and caspase-8 and plays an important role in the vertical infection of S. aureus L-form to affect fetal growth and development.

Apoptosis ; Bacterial Toxins ; toxicity ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; L Forms ; Staphylococcal Infections ; Staphylococcus aureus ; Tumor Necrosis Factor-alpha ; metabolism

We investigated the distribution of commensal staphylococcal species and determined the prevalence of multi-drug resistance in healthy cats and dogs. Risk factors associated with the carriage of multi-drug resistant strains were explored. Isolates from 256 dogs and 277 cats were identified at the species level using matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The diversity of coagulase-negative Staphylococci (CNS) was high, with 22 species in dogs and 24 in cats. Multi-drug resistance was frequent (17%) and not always associated with the presence of the mecA gene. A stay in a veterinary clinic in the last year was associated with an increased risk of colonisation by multi-drug resistant Staphylococci (OR = 2.4, 95% CI: 1.1~5.2, p value LRT = 0.04). When identifying efficient control strategies against antibiotic resistance, the presence of mechanisms other than methicillin resistance and the possible role of CNS in the spread of resistance determinants should be considered.
Animals ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/genetics/metabolism ; Cat Diseases/epidemiology/*microbiology ; Cats ; Coagulase/genetics/metabolism ; Dog Diseases/epidemiology/*microbiology ; Dogs ; *Drug Resistance, Multiple, Bacterial ; Female ; Male ; Prevalence ; Risk Factors ; Seasons ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/veterinary ; Staphylococcal Infections/epidemiology/microbiology/*veterinary ; Staphylococcus/classification/genetics/*isolation & purification ; Switzerland/epidemiology

Although pandemic community-associated (CA-) methicillin-resistant Staphylococcus aureus (MRSA) ST30 clone has successfully spread into many Asian countries, there has been no case in Korea. We report the first imported case of infection caused by this clone in a Korean traveler returning from the Philippines. A previously healthy 30-yr-old Korean woman developed a buttock carbuncle while traveling in the Philippines. After coming back to Korea, oral cephalosporin was given by a primary physician without any improvement. Abscess was drained and MRSA strain isolated from her carbuncle was molecularly characterized and it was confirmed as ST30-MRSA-IV. She was successfully treated with vancomycin and surgery. Frequent international travel and migration have increased the risk of international spread of CA-MRSA clones. The efforts to understand the changing epidemiology of CA-MRSA should be continued, and we should raise suspicion of CA-MRSA infection in travelers with skin infections returning from CA-MRSA-endemic countries.
Adult ; Bacterial Toxins/metabolism ; Carbuncle/microbiology ; Cephalosporins/therapeutic use ; Community-Acquired Infections/drug therapy/microbiology ; Exotoxins/metabolism ; Female ; Humans ; Leukocidins/metabolism ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus/*isolation & purification ; Philippines ; Republic of Korea ; Staphylococcal Skin Infections/*drug therapy/surgery ; Travel ; Vancomycin/therapeutic use