scholarly journals Platelet-Dependent Neutrophil Function Is Dysregulated by M Protein from Streptococcus pyogenes

2015 ◽  
Vol 83 (9) ◽  
pp. 3515-3525 ◽  
Author(s):  
Sinéad M. Hurley ◽  
Fredrik Kahn ◽  
Pontus Nordenfelt ◽  
Matthias Mörgelin ◽  
Ole E. Sørensen ◽  
...  
Keyword(s):  
Complex Formation ◽  
Streptococcus Pyogenes ◽  
Streptococcal Infection ◽  
Neutrophil Function ◽  
Bacterial Killing ◽  
Content Type ◽  
Sepsis And Septic Shock ◽  
Neutrophil Dysfunction ◽  
Chemotactic Ability

Platelets are rapidly responsive sentinel cells that patrol the bloodstream and contribute to the host response to infection. Platelets have been reported to form heterotypic aggregates with leukocytes and may modulate their function. Here, we have investigated platelet-neutrophil complex formation and neutrophil function in response to distinct agonists. The endogenous platelet activator thrombin gave rise to platelet-dependent neutrophil activation, resulting in enhanced phagocytosis and bacterial killing.Streptococcus pyogenesis an important causative agent of severe infectious disease, which can manifest as sepsis and septic shock. M1 protein fromS. pyogenesalso mediated platelet-neutrophil complex formation; however, these neutrophils were dysfunctional and exhibited diminished chemotactic ability and bacterial killing. This reveals an important agonist-dependent neutrophil dysfunction during platelet-neutrophil complex formation and highlights the role of platelets during the immune response to streptococcal infection.

scholarly journals Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children

2016 ◽  
Vol 23 (7) ◽  
pp. 601-609 ◽  
Author(s):  
James J. Gilchrist ◽  
Jennifer N. Heath ◽  
Chisomo L. Msefula ◽  
Esther N. Gondwe ◽  
Vivek Naranbhai ◽  
...  
Keyword(s):  
Principal Component ◽  
Neutrophil Function ◽  
Cytokine Profile ◽  
Severe Malnutrition ◽  
Fatal Disease ◽  
Content Type ◽  
African Children ◽  
Cytokine Responses ◽  
Hiv Coinfection

NontyphoidalSalmonellais a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidalSalmonella(iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n= 111) and in convalescence (n= 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis.

scholarly journals Serine/Threonine Protein Kinase Stk Is Required for Virulence, Stress Response, and Penicillin Tolerance in Streptococcus pyogenes

2011 ◽  
Vol 79 (10) ◽  
pp. 4201-4209 ◽  
Author(s):  
Julia Bugrysheva ◽  
Barbara J. Froehlich ◽  
Jeffrey A. Freiberg ◽  
June R. Scott
Keyword(s):  
Streptococcus Pyogenes ◽  
Fatty Acid Biosynthesis ◽  
Group A Streptococcus ◽  
Acid Biosynthesis ◽  
Regulation Of Expression ◽  
Content Type ◽  
Reverse Transcription Pcr ◽  
Genes Encoding ◽  
Group A

ABSTRACTGenes encoding one or more Ser/Thr protein kinases have been identified recently in many bacteria, including one (stk) in the human pathogenStreptococcus pyogenes(group A streptococcus [GAS]). We report that in GAS,stkis required to produce disease in a murine myositis model of infection. Using microarray and quantitative reverse transcription-PCR (qRT-PCR) studies, we found that Stk activates genes for virulence factors, osmoregulation, metabolism of α-glucans, and fatty acid biosynthesis, as well as genes affecting cell wall synthesis. Confirming these transcription studies, we determined that thestkdeletion mutant is more sensitive to osmotic stress and to penicillin than the wild type. We discuss several possible Stk phosphorylation targets that might explain Stk regulation of expression of specific operons and the possible role of Stk in resuscitation from quiescence.

scholarly journals Hand, foot and mouth disease associated with streptococcus infection in a child (clinical case)

2021 ◽  
Vol 13 (1) ◽  
pp. 124-129
Author(s):  
I. L. Horishna ◽  
L. A. Volyanskaya ◽  
O. N. Dyvonyak ◽  
O. R. Boyarchuk ◽  
E. I. Burbela ◽  
...  
Keyword(s):  
Primary School ◽  
Streptococcus Pyogenes ◽  
Clinical Case ◽  
Streptococcal Infection ◽  
Dominant Role ◽  
Foot And Mouth Disease ◽  
School Age ◽  
Primary School Age ◽  
Typical Localization

In the presented clinical case, the combination of two pathogens (enterovirus and streptococcus) caused a severe and atypical course of the hand-foot-mouth syndrome in a child of primary school age. EVI from the first days of the disease represented by the typical localization of the primary elements of the rash and the characteristic intoxication syndrome was confirmed by the detection of enterovirus RNA in the feces. The course of the disease was undulating. In the first wave, skin rashes accompanied by soreness and itching corresponded to the classical EVI in terms of the nature of the elements, their localization and were combined with lesions of the epithelium of the oral mucosa. Starting from the 5th day of the disease, against the background of an increase in the severity of intoxication syndrome, bullous elements appeared on the skin of the extremities, an excess of the permissible values of antistreptolysin-O was found 12 times, and when sowing material from cracks in the corner of the mouth, Streptococcus pyogenes 106 KUO was isolated, which indicated a combination of the syndrome Hand-foot-mouth with streptococcal infection. Onychomadesis in the period of convalescence retrospectively testified to the dominant role of enterovirus in the presented clinical case.

scholarly journals Colistin Heteroresistance and Involvement of the PmrAB Regulatory System inAcinetobacter baumannii

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Yannick Charretier ◽  
Seydina M. Diene ◽  
Damien Baud ◽  
Sonia Chatellier ◽  
Emmanuelle Santiago-Allexant ◽  
...  
Keyword(s):  
Population Analysis ◽  
Regulatory System ◽  
Reference Method ◽  
Clinical Problem ◽  
Compensatory Mutation ◽  
Regulatory Pathway ◽  
Colistin Resistance ◽  
Bacterial Killing ◽  
Content Type

ABSTRACTMultidrug-resistantAcinetobacter baumanniiinfection has recently emerged as a worldwide clinical problem, and colistin is increasingly being used as a last-resort therapy. Despite its favorable bacterial killing, resistance and heteroresistance (HR) to colistin have been described. The purpose of the present study was to investigate the role of the PmrAB regulatory pathway in laboratory-selected mutants representative of global epidemic strains. From three unrelatedA. baumanniiclinical strains (sequence types 2, 3, and 20), eight colistin-resistant mutants were selected. Half of the mutants showed HR to colistin according to the reference method (population analysis profiling), whereas the other half exhibited stable resistance. M12I mutation withinpmrAand M308R, S144KLAGS, and P170L mutations forpmrBwere associated with HR to colistin, while T235I, A226T, and P233S mutations withinpmrBwere associated with stable resistance. The transcript levels of thepmrCABoperon were upregulated in all the mutants. Compensatory mutations were explored for some mutants. A single mutant (T235I mutant) displayed a compensatory mutation through ISAba1mobilization within thepmrBgene that was associated with the loss of colistin resistance. The mutant resistance phenotype associated with T235I was partially restored in atrans-complementation assay turning to HR. The level of colistin resistance was correlated with the level of expression ofpmrCin thetrans-complemented strains. This report shows the role of different mutations in the PmrAB regulatory pathway and warns of the development of colistin HR that could be present but not easily detected through routine testing.

scholarly journals Role of Glutathione in Buffering Excess Intracellular Copper in Streptococcus pyogenes

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Louisa J. Stewart ◽  
Cheryl-lynn Y. Ong ◽  
May M. Zhang ◽  
Stephan Brouwer ◽  
Liam McIntyre ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Metal Binding ◽  
Metal Ion ◽  
Physiological Role ◽  
Metal Availability ◽  
Content Type ◽  
Bacterial Physiology ◽  
Group A

ABSTRACT Copper (Cu) is an essential metal for bacterial physiology but in excess it is bacteriotoxic. To limit Cu levels in the cytoplasm, most bacteria possess a transcriptionally responsive system for Cu export. In the Gram-positive human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]), this system is encoded by the copYAZ operon. This study demonstrates that although the site of GAS infection represents a Cu-rich environment, inactivation of the copA Cu efflux gene does not reduce virulence in a mouse model of invasive disease. In vitro, Cu treatment leads to multiple observable phenotypes, including defects in growth and viability, decreased fermentation, inhibition of glyceraldehyde-3-phosphate dehydrogenase (GapA) activity, and misregulation of metal homeostasis, likely as a consequence of mismetalation of noncognate metal-binding sites by Cu. Surprisingly, the onset of these effects is delayed by ∼4 h even though expression of copZ is upregulated immediately upon exposure to Cu. Further biochemical investigations show that the onset of all phenotypes coincides with depletion of intracellular glutathione (GSH). Supplementation with extracellular GSH replenishes the intracellular pool of this thiol and suppresses all the observable effects of Cu treatment. These results indicate that GSH buffers excess intracellular Cu when the transcriptionally responsive Cu export system is overwhelmed. Thus, while the copYAZ operon is responsible for Cu homeostasis, GSH has a role in Cu tolerance and allows bacteria to maintain metabolism even in the presence of an excess of this metal ion. IMPORTANCE The control of intracellular metal availability is fundamental to bacterial physiology. In the case of copper (Cu), it has been established that rising intracellular Cu levels eventually fill the metal-sensing site of the endogenous Cu-sensing transcriptional regulator, which in turn induces transcription of a copper export pump. This response caps intracellular Cu availability below a well-defined threshold and prevents Cu toxicity. Glutathione, abundant in many bacteria, is known to bind Cu and has long been assumed to contribute to bacterial Cu handling. However, there is some ambiguity since neither its biosynthesis nor uptake is Cu-regulated. Furthermore, there is little experimental support for this physiological role of glutathione beyond measuring growth of glutathione-deficient mutants in the presence of Cu. Our work with group A Streptococcus provides new evidence that glutathione increases the threshold of intracellular Cu availability that can be tolerated by bacteria and thus advances fundamental understanding of bacterial Cu handling.

scholarly journals NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

2012 ◽  
Vol 80 (7) ◽  
pp. 2558-2569 ◽  
Author(s):  
Balamayooran Theivanthiran ◽  
Sanjay Batra ◽  
Gayathriy Balamayooran ◽  
Shanshan Cai ◽  
Koichi Kobayashi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Host Defense ◽  
The United States ◽  
Bacterial Burden ◽  
Bacterial Killing ◽  
Ligand Interaction ◽  
Chemokine Production ◽  
Content Type ◽  
E Coli

ABSTRACTBacterial pneumonia remains a significant cause of mortality in the United States. The innate immune response is the first line of defense against invading bacteria. Neutrophil recruitment to the lungs is the first step in a multistep sequence leading to bacterial clearance. Ligand interaction with pattern-recognizing receptors (PRRs) leads to chemokine production, which drives neutrophils to the site of infection. Although we demonstrated that RIP2 is important for host defense in the lungs againstEscherichia coli, the individual roles of NOD1 and NOD2 in pulmonary defense have not been addressed. Here, we explored the role of NOD2 in neutrophil-mediated host defense against an extracellular pathogen,E. coli. We found enhanced bacterial burden and reduced neutrophil and cytokine/chemokine levels in the lungs of NOD2−/−mice followingE. coliinfection. Furthermore, we observed reduced activation of NF-κB and mitogen-activated protein kinases (MAPKs) in the lungs of NOD2−/−mice uponE. colichallenge. Moreover, NOD2−/−neutrophils show impaired intracellular bacterial killing. Using NOD2/RIP2−/−mice, we observed bacterial burden and neutrophil accumulation in the lungs similar to those seen with NOD2−/−mice. In addition, bone marrow-derived macrophages obtained from NOD2/RIP2−/−mice demonstrate a reduction in activation of NF-κB and MAPKs similar to that seen with NOD2−/−mice in response toE. coli. These findings unveil a previously unrecognized role of the NOD2-RIP2 axis for host defense against extracellular Gram-negative bacteria. This pathway may represent a novel target for the treatment of lung infection/inflammation.

scholarly journals Circulating Neutrophil Dysfunction in HBV-Related Acute-on-Chronic Liver Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Wu ◽  
Shanshan Sun ◽  
Yijie Wang ◽  
Ruihong Zhao ◽  
Haotang Ren ◽  
...  
Keyword(s):  
Liver Failure ◽  
Neutrophil Function ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Poor Outcome ◽  
The Impact ◽  
Neutrophil Dysfunction ◽  
Aclf Patient

Background and AimsAcute-on-chronic liver failure (ACLF) is characterized by systemic inflammation accompanied by defective anti-bacterial immunity. The role of neutrophils in immune derangement of ACLF has not been fully elucidated. This study is aimed to characterize the role of circulating neutrophils in HBV-related ACLF patients.MethodsQuantitative, phenotypic, transcriptomic, and functional alterations of circulating neutrophils were compared in ACLF and non-ACLF subjects and analyzed for associations with short-term outcomes. Interventional experiments were performed to test the impact on ACLF-patient neutrophil function in vitro.ResultsCirculating absolute neutrophil count was significantly increased in patients with ACLF and was an independent risk factor for 28-day mortality. ACLF-patient neutrophils differentially expressed a panel of surface markers (include TLR-1, TLR-2, TLR-4, CEACAM-1 and FPR1), as well as a distinct transcriptomic signature. ACLF-neutrophils displayed significantly impaired phagocytosis but an increased capacity to form neutrophil extracellular traps (NETs), which was more pronounced in patients with poor outcome. Healthy neutrophils mimicked functional characteristics of ACLF counterpart after co-cultured with plasma from ACLF patients. The oxidative burst and cytokine production capacities remained unchanged. Plasma GM-CSF, IL-6, IL-8, IL-10, and IP-10 levels, as well as lipopolysaccharide (LPS) concentration, were markedly elevated in ACLF patients but not DAMP molecules HMGB-1 and HSP70. Finally, a glycolysis inhibitor, 2-deoxy-glucose, reduced NET formation of ACLF patients’ neutrophils.ConclusionsCirculating ACLF-patient neutrophils exhibit alterations in number, phenotype, gene expression and function, which was associated with poor outcome and shaped by the ACLF circulatory environment. Inhibiting glycolysis can reverse neutrophil dysfunction in ACLF patients.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery

2004 ◽  
pp. 406-412
Author(s):  
Paul Okunieff ◽  
Michael C. Schell ◽  
Russell Ruo ◽  
E. Ronald Hale ◽  
Walter G. O'Dell ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Control ◽  
Content Type ◽  
Negative Results ◽  
Multiple Metastases ◽  
Extracranial Disease ◽  
Successful Control ◽  
The Brain

✓ The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

Etiology, clinical presentation, laboratory diagnostics, pathogenesis of impetigo and treatment methods

2020 ◽  
pp. 64-70
Author(s):  
Anastasiya Laknitskaya
Keyword(s):  
Streptococcus Pyogenes ◽  
Skin Diseases ◽  
Group A Streptococcus ◽  
Antibiotic Sensitivity ◽  
Antioxidant Defense System ◽  
Laboratory Diagnostics ◽  
Treatment Methods ◽  
Group A ◽  
The Individual

Currently, one of the priority medical and social problems is the optimization of treatment methods for pyoderma associated with Streptococcus pyogenes — group A streptococcus (GAS). To date, the proportion of pyoderma, the etiological factor of which is Streptococcus pyogenes, is about 6 % of all skin diseases and is in the range from 17.9 to 43.9 % of all dermatoses. Role of the bacterial factor in the development of streptococcal pyoderma is obvious. Traditional treatment complex includes antibacterial drugs selected individually, taking into account the antibiotic sensitivity of pathognomonic bacteria, and it is not always effective. Currently implemented immunocorrection methods often do not take into account specific immunological features of the disease, the individual, and the fact that the skin performs the function of not only a mechanical barrier, but it is also an immunocompetent organ. Such an approach makes it necessary to conduct additional studies clarifying the role of factors of innate and adaptive immunity, intercellular mediators and antioxidant defense system, that allow to optimize the treatment of this pathology.

Sign in / Sign up

Export Citation Format

Share Document