scholarly journals Survival of Streptococcus suis in Porcine Blood Is Limited by the Antibody- and Complement-Dependent Oxidative Burst Response of Granulocytes

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Viktoria Rungelrath ◽  
Sophie Öhlmann ◽  
Gottfried Alber ◽  
Wieland Schrödl ◽  
Maren von Köckritz-Blickwede ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Oxidative Burst ◽  
Defense Mechanism ◽  
Ex Vivo ◽  
Streptococcus Suis ◽  
Ros Production ◽  
Bacterial Survival ◽  
Content Type ◽  
Porcine Blood ◽  
Antibody Levels

ABSTRACT Bacteremia is a hallmark of invasive Streptococcus suis infections of pigs, often leading to septicemia, meningitis, or arthritis. An important defense mechanism of neutrophils is the generation of reactive oxygen species (ROS). In this study, we report high levels of ROS production by blood granulocytes after intravenous infection of a pig with high levels of S. suis-specific antibodies and comparatively low levels of bacteremia. This prompted us to investigate the working hypothesis that the immunoglobulin-mediated oxidative burst contributes to the killing of S. suis in porcine blood. Several S. suis strains representing serotypes 2, 7, and 9 proved to be highly susceptible to the oxidative burst intermediate hydrogen peroxide, already at concentrations of 0.001%. The induction of ROS in granulocytes in ex vivo-infected reconstituted blood showed an association with pathogen-specific antibody levels. Importantly, inhibition of ROS production by the NADPH oxidase inhibitor apocynin led to significantly increased bacterial survival in the presence of high specific antibody levels. The oxidative burst rate of granulocytes partially depended on complement activation, as shown by specific inhibition. Furthermore, treatment of IgG-depleted serum with a specific IgM protease or heat to inactivate complement resulted in >3-fold decreased oxidative burst activity and increased bacterial survival in reconstituted porcine blood in accordance with an IgM-complement-oxidative burst axis. In conclusion, this study highlights an important control mechanism of S. suis bacteremia in the natural host: the induction of ROS in blood granulocytes via specific immunoglobulins such as IgM.

scholarly journals Sequential Plasmodium chabaudi and Plasmodium berghei Infections Provide a Novel Model of Severe Malarial Anemia

2012 ◽  
Vol 80 (9) ◽  
pp. 2997-3007 ◽  
Author(s):  
Juliana V. Harris ◽  
Tiffany M. Bohr ◽  
Catherine Stracener ◽  
Mary E. Landmesser ◽  
Vladimir Torres ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Interleukin 10 ◽  
Red Cells ◽  
Second Phase ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Severe Malarial Anemia ◽  
Antibody Levels ◽  
Malarial Anemia

ABSTRACTLack of an adequate animal model ofPlasmodium falciparumsevere malarial anemia (SMA) has hampered the understanding of this highly lethal condition. We developed a model of SMA by infecting C57BL/6 mice withP. chabaudifollowed after recovery byP. bergheiinfection.P. chabaudi/P. berghei-infected mice had an initial 9- to 10-day phase of relatively low parasitemia and severe anemia, followed by a second phase of hyperparasitemia, more profound anemia, reticulocytosis, and death 14 to 21 days after infection.P. chabaudi/P. berghei-infected animals had more intense splenic hematopoiesis, higher interleukin-10 (IL-10)/tumor necrosis factor alpha and IL-12/gamma interferon (IFN-γ) ratios, and higher antibody levels againstP. bergheiandP. chabaudiantigens thanP. berghei-infected orP. chabaudi-recovered animals. Early treatment with chloroquine or artesunate did not prevent the anemia, suggesting that the bulk of red cell destruction was not due to the parasite. Red cells fromP. chabaudi/P. berghei-infected animals had increased surface IgG and C3 by flow cytometry. However, C3−/−mice still developed anemia. Tracking of red cells labeledex vivoandin vivoand analysis of frozen tissue sections by immunofluorescence microscopy showed that red cells fromP. chabaudi/P. berghei-infected animals were removed at an accelerated rate in the liver by erythrophagocytosis. This model is practical and reproducible, and its similarities withP. falciparumSMA in humans makes it an appealing system with which to study the pathogenesis of this condition and explore potential immunomodulatory interventions.

scholarly journals Neisseria gonorrhoeae Evades Calprotectin-Mediated Nutritional Immunity and Survives Neutrophil Extracellular Traps by Production of TdfH

2016 ◽  
Vol 84 (10) ◽  
pp. 2982-2994 ◽  
Author(s):  
Sophonie Jean ◽  
Richard A. Juneau ◽  
Alison K. Criss ◽  
Cynthia N. Cornelissen
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Defense Mechanism ◽  
Outer Membrane Proteins ◽  
Neutrophil Extracellular Traps ◽  
Host Protein ◽  
Dependent Manner ◽  
Bacterial Survival ◽  
Content Type ◽  
Extracellular Traps ◽  
Nutritional Immunity

Neisseria gonorrhoeaesuccessfully overcomes host strategies to limit essential nutrients, termed nutritional immunity, by production of TonB-dependent transporters (TdTs)—outer membrane proteins that facilitate nutrient transport in an energy-dependent manner. Four gonococcal TdTs facilitate utilization of iron or iron chelates from host-derived proteins, including transferrin (TbpA), lactoferrin (LbpA), and hemoglobin (HpuB), in addition to xenosiderophores from other bacteria (FetA). The roles of the remaining four uncharacterized TdTs (TdfF, TdfG, TdfH, and TdfJ) remain elusive. Regulatory data demonstrating that production of gonococcal TdfH and TdfJ are unresponsive to or upregulated under iron-replete conditions led us to evaluate the role of these TdTs in the acquisition of nutrients other than iron. In this study, we found that production of gonococcal TdfH is both Zn and Zur repressed. We also found that TdfH confers resistance to calprotectin, an immune effector protein highly produced in neutrophils that has antimicrobial activity due to its ability to sequester Zn and Mn. We found that TdfH directly binds calprotectin, which enables gonococcal Zn accumulation in a TdfH-dependent manner and enhances bacterial survival after exposure to neutrophil extracellular traps (NETs). These studies highlight Zn sequestration by calprotectin as a key functional arm of NET-mediated killing of gonococci. We demonstrate for the first time thatN. gonorrhoeaeexploits this host strategy in a novel defense mechanism, in which TdfH production hijacks and directly utilizes the host protein calprotectin as a zinc source and thereby evades nutritional immunity.

scholarly journals Characterization of Five Zoonotic Streptococcus suis Strains from Germany, Including One Isolate from a Recent Fatal Case of Streptococcal Toxic Shock-Like Syndrome in a Hunter

2015 ◽  
Vol 53 (12) ◽  
pp. 3912-3915 ◽  
Author(s):  
Tobias Eisenberg ◽  
Christoph Hudemann ◽  
Hamid M. Hossain ◽  
Angela Hewer ◽  
Khodr Tello ◽  
...  
Keyword(s):  
Human Blood ◽  
Ex Vivo ◽  
Fatal Case ◽  
Streptococcus Suis ◽  
Toxic Shock ◽  
Blood Samples ◽  
Content Type ◽  
Human Blood Samples ◽  
Low Levels

AStreptococcus suisisolate from a German hunter with streptococcal toxic shock-like syndrome (STSLS) and four additional zoonotic isolates were genotyped asmrp+epf* (variant 1890)sly+cps2+. All five zoonotic German strains were characterized by high multiplication in human blood samplesex vivo, but induction of only low levels of proinflammatory cytokines compared to a Chinese STSLS strain.

scholarly journals Serine-Aspartate Repeat Protein D Increases Staphylococcus aureus Virulence and Survival in Blood

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Fatemeh Askarian ◽  
Satoshi Uchiyama ◽  
J. Andrés Valderrama ◽  
Clement Ajayi ◽  
Johanna U. E. Sollid ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Infection Model ◽  
Bacterial Survival ◽  
Bacterial Killing ◽  
Content Type ◽  
Repeat Protein

ABSTRACT Staphylococcus aureus expresses a panel of cell wall-anchored adhesins, including proteins belonging to the microbial surface components recognizing adhesive matrix molecule (MSCRAMM) family, exemplified by the serine-aspartate repeat protein D (SdrD), which serve key roles in colonization and infection. Deletion of sdrD from S. aureus subsp. aureus strain NCTC8325-4 attenuated bacterial survival in human whole blood ex vivo, which was associated with increased killing by human neutrophils. Remarkably, SdrD was able to inhibit innate immune-mediated bacterial killing independently of other S. aureus proteins, since addition of recombinant SdrD protein and heterologous expression of SdrD in Lactococcus lactis promoted bacterial survival in human blood. SdrD contributes to bacterial virulence in vivo, since fewer S. aureus subsp. aureus NCTC8325-4 ΔsdrD bacteria than bacteria of the parent strain were recovered from blood and several organs using a murine intravenous infection model. Collectively, our findings reveal a new property of SdrD as an important key contributor to S. aureus survival and the ability to escape the innate immune system in blood.

scholarly journals Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Marwan Ghanem ◽  
Jean-Yves Dubé ◽  
Joyce Wang ◽  
Fiona McIntosh ◽  
Daniel Houle ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Virulence Factors ◽  
Ex Vivo ◽  
Nontuberculous Mycobacterium ◽  
Specific Gene ◽  
Bacterial Survival ◽  
Mycobacterium Kansasii ◽  
Content Type ◽  
Lipid Species

ABSTRACT Mycobacterium kansasii is an environmental nontuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the Mycobacterium tuberculosis complex. Using M. kansasii as a proxy for the M. kansasii-M. tuberculosis common ancestor, we asked whether introducing the M. tuberculosis-specific gene pair Rv3377c-Rv3378c into M. kansasii affects the course of experimental infection. Expression of these genes resulted in the production of an adenosine-linked lipid species, known as 1-tuberculosinyladenosine (1-TbAd), but did not alter growth in vitro under standard conditions. Production of 1-TbAd enhanced growth of M. kansasii under acidic conditions through a bacterial cell-intrinsic mechanism independent of controlling pH in the bulk extracellular and intracellular spaces. Production of 1-TbAd led to greater burden of M. kansasii in the lungs of C57BL/6 mice during the first 24 h after infection, and ex vivo infections of alveolar macrophages recapitulated this phenotype within the same time frame. However, in long-term infections, production of 1-TbAd resulted in impaired bacterial survival in both C57BL/6 mice and Ccr2−/− mice. We have demonstrated that M. kansasii is a valid surrogate of M. tuberculosis to study virulence factors acquired by the latter organism, yet shown the challenge inherent to studying the complex evolution of mycobacterial pathogenicity with isolated gene complementation. IMPORTANCE This work sheds light on the role of the lipid 1-tuberculosinyladenosine in the evolution of an environmental ancestor to M. tuberculosis. On a larger scale, it reinforces the importance of horizontal gene transfer in bacterial evolution and examines novel models and methods to provide a better understanding of the subtle effects of individual M. tuberculosis-specific virulence factors in infection settings that are relevant to the pathogen.

scholarly journals The msaABCR Operon Regulates the Response to Oxidative Stress in Staphylococcus aureus

2019 ◽  
Vol 201 (21) ◽  
Author(s):  
Shanti Pandey ◽  
Gyan S. Sahukhal ◽  
Mohamed O. Elasri
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Defense Mechanism ◽  
Ex Vivo ◽  
Carotenoid Pigment ◽  
Content Type ◽  
Staphylococcal Infections ◽  
Organic Hydroperoxides

ABSTRACT Staphylococcus aureus has evolved a complex regulatory network that controls a multitude of defense mechanisms against the deleterious effects of oxidative stress stimuli, subsequently leading to the pathogen’s survival and persistence in the hosts. Previously, we characterized the msaABCR operon as a regulator of virulence, antibiotic resistance, and the formation of persister cells in S. aureus. Deletion of the msaABCR operon resulted in the downregulation of several genes involved in resistance against oxidative stress. Notably, those included carotenoid biosynthetic genes and the ohr gene, which is involved in resistance against organic hydroperoxides. These findings led us to hypothesize that the msaABCR operon is involved in resisting oxidative stress generated in the presence of both H2O2 and organic hydroperoxides. Here, we report that a protein product of the msaABCR operon (MsaB) transcriptionally regulates the expression of the crtOPQMN operon and the ohr gene to resist in vitro oxidative stresses. In addition to its direct regulation of the crtOPQMN operon and ohr gene, we also show that MsaB is the transcriptional repressor of sarZ (repressor of ohr). Taken together, these results suggest that the msaABCR operon regulates an oxidative stress defense mechanism, which is required to facilitate persistent and recurrent staphylococcal infections. Moving forward, we plan to investigate the role of msaABCR in the persistence of S. aureus under in vivo conditions. IMPORTANCE This study shows the involvement of the msaABCR operon in resisting oxidative stress by Staphylococcus aureus generated under in vitro and ex vivo conditions. We show that MsaB regulates the expression and production of a carotenoid pigment, staphyloxanthin, which is a potent antioxidant in S. aureus. We also demonstrate that MsaB regulates the ohr gene, which is involved in defending against oxidative stress generated by organic hydroperoxides. This study highlights the importance of msaABCR in the survival of S. aureus in the presence of various environmental stimuli that mainly exert oxidative stress. The findings from this study indicate the possibility that msaABCR is involved in the persistence of staphylococcal infections and therefore could be a potential antimicrobial target to overcome recalcitrant staphylococcal infections.

scholarly journals Burkholderia pseudomallei Triggers Altered Inflammatory Profiles in a Whole-Blood Model of Type 2 Diabetes-Melioidosis Comorbidity

2012 ◽  
Vol 80 (6) ◽  
pp. 2089-2099 ◽  
Author(s):  
Jodie Morris ◽  
Natasha Williams ◽  
Catherine Rush ◽  
Brenda Govan ◽  
Kunwarjit Sangla ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Oxidative Burst ◽  
Whole Blood ◽  
Burkholderia Pseudomallei ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Bacterial Load ◽  
Activation Markers ◽  
Content Type

ABSTRACTMelioidosis is a potentially fatal disease caused by the bacteriumBurkholderia pseudomallei. Type 2 diabetes (T2D) is the most common comorbidity associated with melioidosis.B. pseudomalleiisolates from melioidosis patients with T2D are less virulent in animal models than those from patients with melioidosis and no identifiable risk factors. We developed anex vivowhole-blood assay as a tool for comparison of early inflammatory profiles generated by T2D and nondiabetic (ND) individuals in response to aB. pseudomalleistrain of low virulence. Peripheral blood from individuals with T2D, with either poorly controlled glycemia (PC-T2D [n= 6]) or well-controlled glycemia (WC-T2D [n= 8]), and healthy ND (n= 13) individuals was stimulated withB. pseudomallei. Oxidative burst, myeloperoxidase (MPO) release, expression of pathogen recognition receptors (TLR2, TLR4, and CD14), and activation markers (CD11b and HLA-DR) were measured on polymorphonuclear (PMN) leukocytes and monocytes. Concentrations of plasma inflammatory cytokine (interleukin-6 [IL-6], IL-12p70, tumor necrosis factor alpha [TNF-α], monocyte chemoattractant protein 1 [MCP-1], IL-8, IL-1β, and IL-10) were also determined. Following stimulation, oxidative burst and MPO levels were significantly elevated in blood from PC-T2D subjects compared to controls. Differences were also observed in expression of Toll-like receptor 2 (TLR2), CD14, and CD11b on phagocytes from T2D and ND individuals. Levels of IL-12p70, MCP-1, and IL-8 were significantly elevated in blood from PC-T2D subjects compared to ND individuals. Notably, differential inflammatory responses of PC-T2D, WC-T2D, and ND individuals toB. pseudomalleioccur independently of bacterial load and confirm the efficacy of this model of T2D-melioidosis comorbidity as a tool for investigation of dysregulated PMN and monocyte responses toB. pseudomalleiunderlying susceptibility of T2D individuals to melioidosis.

scholarly journals Antibodies to a Novel Leptospiral Protein, LruC, in the Eye Fluids and Sera of Horses with Leptospira-Associated Uveitis

2012 ◽  
Vol 19 (3) ◽  
pp. 452-456 ◽  
Author(s):  
Ashutosh Verma ◽  
James Matsunaga ◽  
Sergey Artiushin ◽  
Marija Pinne ◽  
Dirk J. Houwers ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Specific Antibody ◽  
Leptospira Interrogans ◽  
Expression Library ◽  
Content Type ◽  
Antibody Levels ◽  
Novel Protein

ABSTRACTScreening of an expression library ofLeptospira interroganswith eye fluids from uveitic horses resulted in identification of a novel protein, LruC. LruC is located in the inner leaflet of the leptospiral outer membrane, and anlruCgene was detected in all tested pathogenicL. interrogansstrains. LruC-specific antibody levels were significantly higher in eye fluids and sera of uveitic horses than healthy horses. These findings suggest that LruC may play a role in equine leptospiral uveitis.

scholarly journals Use of Proteins Identified through a Functional Genomic Screen To Develop a Protein Subunit Vaccine That Provides Significant Protection against Virulent Streptococcus suis in Pigs

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Susan L. Brockmeier ◽  
Crystal L. Loving ◽  
Tracy L. Nicholson ◽  
Jinhong Wang ◽  
Sarah E. Peters ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Trial ◽  
Streptococcus Suis ◽  
Protein Subunit ◽  
Content Type ◽  
Degree Of Protection ◽  
Wide Range ◽  
Associated Proteins ◽  
Clinical Protection ◽  
Cellular Immune

ABSTRACT Streptococcus suis is a bacterium that is commonly carried in the respiratory tract and that is also one of the most important invasive pathogens of swine, commonly causing meningitis, arthritis, and septicemia. Due to the existence of many serotypes and a wide range of immune evasion capabilities, efficacious vaccines are not readily available. The selection of S. suis protein candidates for inclusion in a vaccine was accomplished by identifying fitness genes through a functional genomics screen and selecting conserved predicted surface-associated proteins. Five candidate proteins were selected for evaluation in a vaccine trial and administered both intranasally and intramuscularly with one of two different adjuvant formulations. Clinical protection was evaluated by subsequent intranasal challenge with virulent S. suis . While subunit vaccination with the S. suis proteins induced IgG antibodies to each individual protein and a cellular immune response to the pool of proteins and provided substantial protection from challenge with virulent S. suis , the immune response elicited and the degree of protection were dependent on the parenteral adjuvant given. Subunit vaccination induced IgG reactive against different S. suis serotypes, indicating a potential for cross protection.

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