scholarly journals IgG4-specific responses in patients with Staphylococcus aureus bone infections are not predictive of postoperative complications

2021 ◽  
Vol 42 ◽  
pp. 156-165
Author(s):  
JR Owen ◽  
◽  
MP Campbell ◽  
MD Mott ◽  
CA Beck ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Adverse Outcome ◽  
Host Factors ◽  
Healthy Controls ◽  
Complement Inhibitor ◽  
Inhibitory Protein ◽  
Blood Samples ◽  
Bone Infections ◽  
Prevalent Pathogen

The most prevalent pathogen in bone infections is Staphylococcus aureus; its incidence and severity are partially determined by host factors. Prior studies showed that anti-glucosaminidase (Gmd) antibodies are protective in animals, and 93.3 % of patients with culture-confirmed S. aureus osteomyelitis do not have anti-Gmd levels > 10 ng/mL in serum. Infection in patients with high anti-Gmd remains unexplained. Are anti-Gmd antibodies in osteomyelitis patients of the non-opsonising, non-complement-fixing IgG4 isotype? The relative amounts of IgG4 and total IgG against Gmd and 7 other S. aureus antigens: iron-surface determinants (Isd) IsdA, IsdB, and IsdH, amidase (Amd), α-haemolysin (Hla), chemotaxis inhibitory protein from S. aureus (CHIPS), and staphylococcal-complement inhibitor (SCIN) were determined in sera from healthy controls (Ctrl, n = 92), osteomyelitis patients whose surgical treatment resulted in infection control (IC, n = 95) or an adverse outcome (AD, n = 40), and post-mortem (PM, n = 7) blood samples from S. aureus septic-death patients. Anti-Gmd IgG4 levels were generally lower in infected patients compared to controls; however, levels among the infected were higher in AD than IC patients. Anti-IsdA, IsdB and IsdH IgG4 levels were increased in infected patients versus controls, and Jonckheere-Terpstra tests of levels revealed an increasing order of infection (Ctrl < IC < AD < PM) for anti-Isd IgG4 antibodies and a decreasing order of infection (Ctrl > IC > AD > PM) for anti-autolysin (Atl) IgG4 antibodies. Collectively, this does not support an immunosuppressive role of IgG4 in S. aureus osteomyelitis but is consistent with a paradigm of high anti-Isd and low anti-Atl responses in these patients.

scholarly journals The Innate Immune Modulators Staphylococcal Complement Inhibitor and Chemotaxis Inhibitory Protein of Staphylococcus aureus Are Located on β-Hemolysin-Converting Bacteriophages

2006 ◽  
Vol 188 (4) ◽  
pp. 1310-1315 ◽  
Author(s):  
Willem J. B. van Wamel ◽  
Suzan H. M. Rooijakkers ◽  
Maartje Ruyken ◽  
Kok P. M. van Kessel ◽  
Jos A. G. van Strijp
Keyword(s):  
Staphylococcus Aureus ◽  
Mitomycin C ◽  
Immune Evasion ◽  
Innate Immune ◽  
Complement Inhibitor ◽  
Inhibitory Protein ◽  
Immune Modulators ◽  
Phage Dna ◽  
Innate Immune Evasion ◽  
Human Specific

ABSTRACT Two newly discovered immune modulators, chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) and staphylococcal complement inhibitor (SCIN), cluster on the conserved 3′ end of β-hemolysin (hlb)-converting bacteriophages (βC-φs). Since these βC-φs also carry the genes for the immune evasion molecules staphylokinase (sak) and enterotoxin A (sea), this 8-kb region at the 3′ end of βC-φ represents an innate immune evasion cluster (IEC). By PCR and Southern analyses of 85 clinical Staphylococcus aureus strains and 5 classical laboratory strains, we show that 90% of S. aureus strains carry a βC-φ with an IEC. Seven IEC variants were discovered, carrying different combinations of chp, sak, or sea (or sep), always in the same 5′-to-3′ orientation and on the 3′ end of a βC-φ. From most IEC variants we could isolate active bacteriophages by mitomycin C treatment, of which lysogens were generated in S. aureus R5 (broad phage host). All IEC-carrying bacteriophages integrated into hlb, as was measured by Southern blotting of R5 lysogens. Large quantities of the different bacteriophages were obtained by mitomycin C treatment of the lysogens, and bacteriophages were collected and used to reinfect all lysogenic R5 strains. In total, five lytic families were found. Furthermore, phage DNA was isolated and digested with EcoR1, revealing that one IEC variant can be found on different βI-φs. In conclusion, the four human-specific innate immune modulators SCIN, CHIPS, SAK, and SEA form an IEC that is easily transferred among S. aureus strains by a diverse group of β-hemolysin-converting bacteriophages.

scholarly journals Role of Bacterial Exopolymers and Host Factors on Adherence and Phagocytosis of Staphylococcus aureus in Foreign Body Infection

1987 ◽  
Vol 155 (3) ◽  
pp. 524-531 ◽  
Author(s):  
E. Falcieri ◽  
P. Vaudaux ◽  
E. Huggler ◽  
D. Lew ◽  
F. Waldvogel
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Host Factors

scholarly journals Bacterial virulence plays a crucial role in MRSA sepsis

2021 ◽  
Vol 17 (2) ◽  
pp. e1009369
Author(s):  
Gordon Y. C. Cheung ◽  
Justin S. Bae ◽  
Ryan Liu ◽  
Rachelle L. Hunt ◽  
Yue Zheng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Early Stage ◽  
Bacterial Virulence ◽  
Host Factors ◽  
Bacterial Sepsis ◽  
Critical Stage ◽  
Industrialized Nations ◽  
Device Associated Infection

Bacterial sepsis is a major global cause of death. However, the pathophysiology of sepsis has remained poorly understood. In industrialized nations, Staphylococcus aureus represents the pathogen most commonly associated with mortality due to sepsis. Because of the alarming spread of antibiotic resistance, anti-virulence strategies are often proposed to treat staphylococcal sepsis. However, we do not yet completely understand if and how bacterial virulence contributes to sepsis, which is vital for a thorough assessment of such strategies. We here examined the role of virulence and quorum-sensing regulation in mouse and rabbit models of sepsis caused by methicillin-resistant S. aureus (MRSA). We determined that leukopenia was a predictor of disease outcome during an early critical stage of sepsis. Furthermore, in device-associated infection as the most frequent type of staphylococcal blood infection, quorum-sensing deficiency resulted in significantly higher mortality. Our findings give important guidance regarding anti-virulence drug development strategies for the treatment of staphylococcal sepsis. Moreover, they considerably add to our understanding of how bacterial sepsis develops by revealing a critical early stage of infection during which the battle between bacteria and leukocytes determines sepsis outcome. While sepsis has traditionally been attributed mainly to host factors, our study highlights a key role of the invading pathogen and its virulence mechanisms.

scholarly journals Evaluation of Methylation at Promoter Regions of Long Non-coding RNAs in Patients with Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
Zohreh Mousavi ◽  
Saeid Ghorbian ◽  
Azim Rezamand ◽  
Leyla Roshangar ◽  
Behboud Jafari
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Characteristic Curve ◽  
Methylation Status ◽  
Healthy Controls ◽  
Promoter Regions ◽  
Roc Curve Analysis ◽  
Blood Samples ◽  
Non Coding Rnas

Introduction Acute lymphoblastic leukemia (ALL) is a fetal hematologic disorder that is mostly observed in children. Both B and T lymphocytes have been reported to play a role in ALL etiology. Long non-coding RNAs (lncRNAs) are large regulatory molecules with more than 200 nucleotides that participate in various cellular processes. Methylation at the promoter regions of these regulatory molecules has been reported to vary between ALL patients and healthy controls. This study aimed to evaluate methylation status at promoter regions of lncRNAs between these two groups. Methods In the current study, 80 ALL patients and 80 healthy controls were enrolled. The intravenous blood samples were obtained from all patients and controls. The extracted DNA from blood samples underwent sodium bisulfite treatment. Thereafter, methylation levels in the promoter regions of lncRNAs RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were evaluated using methylation specific‑high resolution melting (MS‑HRM). Moreover, the receiver operating characteristic curve (ROC) analysis was performed to examine the sensitivity and specificity of the tests. Results The methylation levels of all studied lncRNAs including RP11-137H2.4 (P =0.001837), RP11-624c23.1 (P = 0.000003), RP11-203E8 (P = 0.000092), RP11-446E9 (P = 0.02447), and RP11-68118.10 (P =0.000086) were significantly increased. ROC curve analysis also showed that all lncRNAs could be used as diagnostic markers. Conclusion This study showed that methylation alterations of lncRNAs could be considered as novel biomarkers for early detection of ALL. Furthermore, owing to the possible role of studied lncRNAs as tumor suppressors, they could be reliable treatment targets for methylation modifications. Further research is still required to elucidate the role of these lncRNAs in ALL etiology.

Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs

1969 ◽  
Vol 21 (02) ◽  
pp. 294-303 ◽  
Author(s):  
H Mihara ◽  
T Fujii ◽  
S Okamoto
Keyword(s):  
Cerebrospinal Fluid ◽  
Carboxylic Acid ◽  
Fibrinolytic Activity ◽  
Clinical Implications ◽  
Trans Form ◽  
Plate Method ◽  
Blood Samples ◽  
Fibrin Plate ◽  
The Brain

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

scholarly journals Blood transcriptome analysis of patients with uncomplicated bacterial infection and sepsis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Velma Herwanto ◽  
Benjamin Tang ◽  
Ya Wang ◽  
Maryam Shojaei ◽  
Marek Nalos ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Healthy Controls ◽  
Beta Globin ◽  
Transcriptome Data ◽  
Valuable Resource ◽  
Globin Mrna ◽  
Blood Samples ◽  
Data Description ◽  
Pathway Activation ◽  
Blood Transcriptome

Abstract Objectives Hospitalized patients who presented within the last 24 h with a bacterial infection were recruited. Participants were assigned into sepsis and uncomplicated infection groups. In addition, healthy volunteers were recruited as controls. RNA was prepared from whole blood, depleted from beta-globin mRNA and sequenced. This dataset represents a highly valuable resource to better understand the biology of sepsis and to identify biomarkers for severe sepsis in humans. Data description The data presented here consists of raw and processed transcriptome data obtained by next generation RNA sequencing from 105 peripheral blood samples from patients with uncomplicated infections, patients who developed sepsis, septic shock patients, and healthy controls. It is provided as raw sequenced reads and as normalized log2 transformed relative expression levels. This data will allow performing detailed analyses of gene expression changes between uncomplicated infections and sepsis patients, such as identification of differentially expressed genes, co-regulated modules as well as pathway activation studies.

scholarly journals Altered DNA methylation pattern reveals epigenetic regulation of Hox genes in thoracic aortic dissection and serves as a biomarker in disease diagnosis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Peiru Liu ◽  
Jing Zhang ◽  
Duo Du ◽  
Dandan Zhang ◽  
Zelin Jin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Aortic Dissection ◽  
Epigenetic Regulation ◽  
Heart Development ◽  
Type A ◽  
Methylation Pattern ◽  
Healthy Controls ◽  
Global Methylation ◽  
Thoracic Aortic Dissection

Abstract Background Thoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examined the role of DNA methylation in the development of TAD. This study explored alterations of the DNA methylation landscape in TAD and examined the potential role of cell-free DNA (cfDNA) methylation as a biomarker in TAD diagnosis. Results Ascending aortic tissues from TAD patients (Stanford type A; n = 6) and healthy controls (n = 6) were first examined via whole-genome bisulfite sequencing (WGBS). While no obvious global methylation shift was observed, numerous differentially methylated regions (DMRs) were identified, with associated genes enriched in the areas of vasculature and heart development. We further confirmed the methylation and expression changes in homeobox (Hox) clusters with 10 independent samples using bisulfite pyrosequencing and quantitative real-time PCR (qPCR). Among these, HOXA5, HOXB6 and HOXC6 were significantly down-regulated in TAD samples relative to controls. To evaluate cfDNA methylation pattern as a biomarker in TAD diagnosis, cfDNA from TAD patients (Stanford type A; n = 7) and healthy controls (n = 4) were examined by WGBS. A prediction model was built using DMRs identified previously from aortic tissues on methylation data from cfDNA. Both high sensitivity (86%) and specificity (75%) were achieved in patient classification (AUC = 0.96). Conclusions These findings showed an altered epigenetic regulation in TAD patients. This altered epigenetic regulation and subsequent altered expression of genes associated with vasculature and heart development, such as Hox family genes, may contribute to the loss of aortic integrity and TAD pathogenesis. Additionally, the cfDNA methylation in TAD was highly disease specific, which can be used as a non-invasive biomarker for disease prediction.

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