Plasma Protein Layer Concealment Protects Streptococcus pyogenes From Innate Immune Attack

Early recognition and elimination of invading pathogens by the innate immune system, is one of the most efficient host defense mechanisms preventing the induction of systemic complications from infection. To this end the host can mobilize endogenous antimicrobials capable of killing the intruder by perforating the microbial cell wall. Here, we show that Streptococcus pyogenes can shield its outer surface with a layer of plasma proteins. This mechanism protects the bacteria from an otherwise lytic attack by LL-37 and extracellular histones, allowing the bacteria to adjust their gene regulation to an otherwise hostile environment.

Download Full-text

Corrigendum: Plasma Protein Layer Concealment Protects Streptococcus pyogenes From Innate Immune Attack

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.752280 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hilger Jagau ◽

Swathi Packirisamy ◽

Kyle Brandon ◽

Heiko Herwald

Keyword(s):

Streptococcus Pyogenes ◽

Plasma Protein ◽

Innate Immune ◽

Protein Layer ◽

Immune Attack

Download Full-text

Streptococcus pyogenes Escapes Killing from Extracellular Histones through Plasminogen Binding and Activation by Streptokinase

Journal of Innate Immunity ◽

10.1159/000448039 ◽

2016 ◽

Vol 8 (6) ◽

pp. 589-600 ◽

Cited By ~ 10

Author(s):

Ramona Nitzsche ◽

Juliane Köhler ◽

Bernd Kreikemeyer ◽

Sonja Oehmcke-Hecht

Keyword(s):

Immune System ◽

Streptococcus Pyogenes ◽

Innate Immune System ◽

Innate Immune ◽

Main Function ◽

Human Pathogen ◽

Antimicrobial Proteins ◽

Basic Proteins ◽

Extracellular Histones

Histones are small basic proteins and highly conserved among eukaryotes. Their main function is binding, packaging and organizing of DNA in the nucleus, but extracellular histones are also potent antimicrobial proteins. Here we found that Streptococcus pyogenes - an important human pathogen - protects itself from histone-killing by the acquisition of plasminogen. Plasminogen, bound to the streptococcal surface, efficiently prevents histone-mediated killing. Moreover, the streptokinase/plasminogen complex degrades all classes of histones and abrogates their antibacterial and hemolytic effects. This novel streptokinase-mediated virulence mechanism may contribute to the escape of S. pyogenes from the human innate immune system.

Download Full-text

The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes

Infection and Immunity ◽

10.1128/iai.00925-16 ◽

2016 ◽

Vol 85 (3) ◽

Cited By ~ 2

Author(s):

Luis A. Vega ◽

Kayla M. Valdes ◽

Ganesh S. Sundar ◽

Ashton T. Belew ◽

Emrul Islam ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Immune Evasion ◽

Immune Cell ◽

Group A Streptococcus ◽

Transcriptional Regulator ◽

Innate Immune ◽

Content Type ◽

Human Host

ABSTRACTAs an exclusively human pathogen,Streptococcus pyogenes(the group A streptococcus [GAS]) has specifically adapted to evade host innate immunity and survive in multiple tissue niches, including blood. GAS can overcome the metabolic constraints of the blood environment and expresses various immunomodulatory factors necessary for survival and immune cell resistance. Here we present our investigation of one such factor, the predicted LysR family transcriptional regulator CpsY. The encoding gene,cpsY, was initially identified as being required for GAS survival in a transposon-site hybridization (TraSH) screen in whole human blood. CpsY is homologous with transcriptional regulators ofStreptococcus mutans(MetR),Streptococcus iniae(CpsY), andStreptococcus agalactiae(MtaR) that regulate methionine transport, amino acid metabolism, resistance to neutrophil-mediated killing, and survivalin vivo. Our investigation indicated that CpsY is involved in GAS resistance to innate immune cells of its human host. However, GAS CpsY does not manifest thein vitrophenotypes of its homologs in other streptococcal species. GAS CpsY appears to regulate a small set of genes that is markedly different from the regulons of its homologs. The differential expression of these genes depends on the growth medium, and CpsY modestly influences their expression. The GAS CpsY regulon includes known virulence factors (mntE,speB,spd,nga[spn],prtS[SpyCEP], andsse) and cell surface-associated factors of GAS (emm1,mur1.2,sibA[cdhA], andM5005_Spy0500). Intriguingly, the loss of CpsY in GAS does not result in virulence defects in murine models of infection, suggesting that CpsY function in immune evasion is specific to the human host.

Download Full-text

Cocaine-induced mesenteric ischaemia requiring small bowel resection

BMJ Case Reports ◽

10.1136/bcr-2020-238593 ◽

2021 ◽

Vol 14 (1) ◽

pp. e238593

Author(s):

Asya Veloso Costa ◽

Asiya Zhunus ◽

Rehana Hafeez ◽

Arsh Gupta

Keyword(s):

Small Bowel ◽

Social History ◽

Bowel Resection ◽

Early Recognition ◽

Small Bowel Resection ◽

Emergency Laparotomy ◽

Mesenteric Ischaemia ◽

Bowel Ischaemia ◽

Systemic Complications ◽

Gastrointestinal Complications

Cocaine use causes profound vasoconstriction leading to various systemic complications. Gastrointestinal complications such as mesenteric ischaemia are difficult to recognise and may result in serious consequences if not treated promptly. We report on the case of a 47-year-old man presenting with mesenteric ischaemia on a background of acute on chronic cocaine consumption, where diagnosis was not evident until second presentation. He underwent an emergency laparotomy with small bowel resection and jejunostomy formation and made a good recovery with eventual reversal surgery. The literature on cocaine-induced bowel ischaemia shows significant variability in presentation and outcome. Laboratory investigations are non-specific, and early recognition is vital. Given the increasing recreational use of cocaine in the UK, it is imperative to have a high clinical index of suspicion for mesenteric ischaemia in patients presenting with non-specific abdominal pain, and to ensure a detailed social history covering recreational drug use is not forgotten.

Download Full-text

Modulation of Innate Immune Responses by the Influenza A NS1 and PA-X Proteins

Viruses ◽

10.3390/v10120708 ◽

2018 ◽

Vol 10 (12) ◽

pp. 708 ◽

Cited By ~ 17

Author(s):

Aitor Nogales ◽

Luis Martinez-Sobrido ◽

David Topham ◽

Marta DeDiego

Keyword(s):

Immune Responses ◽

Influenza A ◽

Defense Mechanisms ◽

Synergistic Effects ◽

Viral Proteins ◽

Economic Problem ◽

Innate Immune ◽

Host Protein ◽

Innate Immune Responses ◽

Influenza A Viruses

Influenza A viruses (IAV) can infect a broad range of animal hosts, including humans. In humans, IAV causes seasonal annual epidemics and occasional pandemics, representing a serious public health and economic problem, which is most effectively prevented through vaccination. The defense mechanisms that the host innate immune system provides restrict IAV replication and infection. Consequently, to successfully replicate in interferon (IFN)-competent systems, IAV has to counteract host antiviral activities, mainly the production of IFN and the activities of IFN-induced host proteins that inhibit virus replication. The IAV multifunctional proteins PA-X and NS1 are virulence factors that modulate the innate immune response and virus pathogenicity. Notably, these two viral proteins have synergistic effects in the inhibition of host protein synthesis in infected cells, although using different mechanisms of action. Moreover, the control of innate immune responses by the IAV NS1 and PA-X proteins is subject to a balance that can determine virus pathogenesis and fitness, and recent evidence shows co-evolution of these proteins in seasonal viruses, indicating that they should be monitored for enhanced virulence. Importantly, inhibition of host gene expression by the influenza NS1 and/or PA-X proteins could be explored to develop improved live-attenuated influenza vaccines (LAIV) by modulating the ability of the virus to counteract antiviral host responses. Likewise, both viral proteins represent a reasonable target for the development of new antivirals for the control of IAV infections. In this review, we summarize the role of IAV NS1 and PA-X in controlling the antiviral response during viral infection.

Download Full-text

Cooperative Immune Suppression by Escherichia coli and Shigella Effector Proteins

Infection and Immunity ◽

10.1128/iai.00560-17 ◽

2018 ◽

Vol 86 (4) ◽

Cited By ~ 6

Author(s):

Maarten F. de Jong ◽

Neal M. Alto

Keyword(s):

Escherichia Coli ◽

Defense Mechanisms ◽

Immune Defense ◽

Effector Proteins ◽

Innate Immune ◽

Host Cells ◽

Secretion Systems ◽

Content Type ◽

E Coli ◽

Type Iii Secretion Systems

ABSTRACT The enteric attaching and effacing (A/E) pathogens enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) and the invasive pathogens enteroinvasive E. coli (EIEC) and Shigella encode type III secretion systems (T3SS) used to inject effector proteins into human host cells during infection. Among these are a group of effectors required for NF-κB-mediated host immune evasion. Recent studies have identified several effector proteins from A/E pathogens and EIEC/ Shigella that are involved in suppression of NF-κB and have uncovered their cellular and molecular functions. A novel mechanism among these effectors from both groups of pathogens is to coordinate effector function during infection. This cooperativity among effector proteins explains how bacterial pathogens are able to effectively suppress innate immune defense mechanisms in response to diverse classes of immune receptor signaling complexes (RSCs) stimulated during infection.

Download Full-text

Physicochemical Studies on Artificial Surface/Protein/Platelet Interactions

10.1055/s-0039-1689328 ◽

1975 ◽

Author(s):

E. Nyilas ◽

T.-H. Chiu ◽

W. A. Morton ◽

D. M. Lederman ◽

G. A. Herzlinger ◽

...

Keyword(s):

Conformational Changes ◽

Plasma Proteins ◽

Platelet Adhesion ◽

Surface Protein ◽

Surface Proteins ◽

Molecular Architecture ◽

Number Density ◽

Protein Layer ◽

Artificial Surface ◽

Lag Period

To highlight the mechanisms of artificial surface/protein/platelet interactions, results obtained by various methods have been integrated to elucidate some of the correlations between phenomena which occur at the macromolecular level and subsequently influence those at the cellular level, such as platelet adhesion. Microcinematographic evidence obtained under the controlled conditions of the Stagnation Point Flow Experiment (SPFE) indicate that, even on glass, platelet adhesion commences only after 30-60 sees of exposure to native blood. This lag period is consistent with diffusion kinetics predicting the arrival of plasma proteins should overhwelmingly precede that of the cellular components. During the lag period, native plasma proteins collide with the artificial surface and, in most cases, adsorb with surface-induced conformational changes. The energy for altering the secondary protein structure is supplied by the heat of adsorption. The extent of adsorption and structural alterations depend upon both the type of protein and the molecular architecture of the artificial surface, viz., the number density and orientation of polar, H-bonding, etc. groups accessible to proteins. Using microparticulate glass (< μ dia.) and a microcalorimeter sensitive to ±0.00001° C in 100 ml of sample volume, serum albumin was found to adsorb, release heat, and desorb in a conformationally altered state. In contrast, γ-(7S)-globulin and fibrinogen underwent irreversible multilayer attachment releasing (1.0-1.7) χ 103 Kcal/mole of protein adsorbed directly to the glass surface. Proteins in the second, etc. sorbed layers released much smaller heats. The electrophoretic mobility of the same particles coated with varying amounts of the same proteins confirmed that the relatively greatest conformational change occurred in the protein layer directly attached to the artificial surface. On homologous Nylons exposed under identical hemodynamic conditions in the SPFE, the surface number density of platelets remaining adherent at points of identical shear was proportionate to the polar force contribution of those surfaces. These results indicate that the protein layer which settles first, is acting as a “proportional transformer” mediating the effects of artificial surfaces onto platelets.

Download Full-text

How to rewire the host cell: A home improvement guide for intracellular bacteria

The Journal of Cell Biology ◽

10.1083/jcb.201701095 ◽

2017 ◽

Vol 216 (12) ◽

pp. 3931-3948 ◽

Cited By ~ 29

Author(s):

Elias Cornejo ◽

Philipp Schlaermann ◽

Shaeri Mukherjee

Keyword(s):

Host Cell ◽

Signaling Pathways ◽

Membrane Trafficking ◽

Defense Mechanisms ◽

Bacterial Pathogens ◽

Innate Immune ◽

Intracellular Bacteria ◽

Immune Signaling ◽

Innate Immune Signaling ◽

The Unfolded Protein Response

Intracellular bacterial pathogens have developed versatile strategies to generate niches inside the eukaryotic cells that allow them to survive and proliferate. Making a home inside the host offers many advantages; however, intracellular bacteria must also overcome many challenges, such as disarming innate immune signaling and accessing host nutrient supplies. Gaining entry into the cell and avoiding degradation is only the beginning of a successful intracellular lifestyle. To establish these replicative niches, intracellular pathogens secrete various virulence proteins, called effectors, to manipulate host cell signaling pathways and subvert host defense mechanisms. Many effectors mimic host enzymes, whereas others perform entirely novel enzymatic functions. A large volume of work has been done to understand how intracellular bacteria manipulate membrane trafficking pathways. In this review, we focus on how intracellular bacterial pathogens target innate immune signaling, the unfolded protein response, autophagy, and cellular metabolism and exploit these pathways to their advantage. We also discuss how bacterial pathogens can alter host gene expression by directly modifying histones or hijacking the ubiquitination machinery to take control of several host signaling pathways.

Download Full-text

Innate Lung Defense during Invasive Aspergillosis: New Mechanisms

Journal of Innate Immunity ◽

10.1159/000455125 ◽

2017 ◽

Vol 9 (3) ◽

pp. 271-280 ◽

Cited By ~ 15

Author(s):

Jaleesa M. Garth ◽

Chad Steele

Keyword(s):

Invasive Aspergillosis ◽

Defense Mechanisms ◽

Fungal Infections ◽

Immunosuppressive Agents ◽

Innate Immune ◽

Pulmonary System ◽

Continued Use ◽

Primary Risk Factor ◽

Primary Agent ◽

Lung Defense

Invasive aspergillosis (IA) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. Continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for IA. However, IA is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. The innate immune response to Aspergillus fumigatus, the primary agent in IA, plays a pivotal role in the recognition and elimination of organisms from the pulmonary system. This review highlights recent findings about innate host defense mechanisms, including novel aspects of innate cellular immunity and pathogen recognition, and the inflammatory mediators that control infection with A. fumigatus.

Download Full-text