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Article ; Online: CXCR2 perturbation promotes

Akaraphanth, Mike / Nordgren, Tara M / Gries, Casey M

2024 Volume 73, Issue 4

Abstract: Introduction. ...

Abstract	Introduction.
MeSH term(s)	Mice ; Animals ; Staphylococcus aureus/physiology ; Methicillin-Resistant Staphylococcus aureus/physiology ; Receptors, Interleukin-8B/genetics ; Staphylococcal Infections/microbiology ; Biofilms ; Pyrimidines ; Sulfonamides
Chemical Substances	N-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamide ; Receptors, Interleukin-8B ; Pyrimidines ; Sulfonamides
Language	English
Publishing date	2024-04-04
Publishing country	England
Document type	Journal Article
ZDB-ID	218356-0
ISSN	1473-5644 ; 0022-2615
ISSN (online)	1473-5644
ISSN	0022-2615
DOI	10.1099/jmm.0.001821
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Zs.A 634: Show issues

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Article ; Online: Beyond Homeostasis: Potassium and Pathogenesis during Bacterial Infections.

Do, Elyza A / Gries, Casey M

Infection and immunity

2021 Volume 89, Issue 7, Page(s) e0076620

Abstract: Potassium is an essential mineral nutrient required by all living cells for normal physiological function. Therefore, maintaining intracellular potassium homeostasis during bacterial infection is a requirement for the survival of both host and pathogen. ... ...

Abstract	Potassium is an essential mineral nutrient required by all living cells for normal physiological function. Therefore, maintaining intracellular potassium homeostasis during bacterial infection is a requirement for the survival of both host and pathogen. However, pathogenic bacteria require potassium transport to fulfill nutritional and chemiosmotic requirements, and potassium has been shown to directly modulate virulence gene expression, antimicrobial resistance, and biofilm formation. Host cells also require potassium to maintain fundamental biological processes, such as renal function, muscle contraction, and neuronal transmission; however, potassium flux also contributes to critical immunological and antimicrobial processes, such as cytokine production and inflammasome activation. Here, we review the role and regulation of potassium transport and signaling during infection in both mammalian and bacterial cells and highlight the importance of potassium to the success and survival of each organism.
MeSH term(s)	Animals ; Bacterial Infections/etiology ; Bacterial Infections/metabolism ; Bacterial Physiological Phenomena ; Cytokines/metabolism ; Disease Susceptibility ; Homeostasis ; Host-Pathogen Interactions/immunology ; Humans ; Inflammasomes/metabolism ; Organ Specificity ; Potassium/metabolism ; Signal Transduction ; Virulence
Chemical Substances	Cytokines ; Inflammasomes ; Potassium (RWP5GA015D)
Language	English
Publishing date	2021-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00766-20
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Article ; Online: Staphylococcal Biofilms and Immune Polarization During Prosthetic Joint Infection.

Gries, Casey M / Kielian, Tammy

The Journal of the American Academy of Orthopaedic Surgeons

2017 Volume 25 Suppl 1, Page(s) S20–S24

Abstract: Staphylococcal species are a leading cause of community- and nosocomial-acquired infections, where the placement of foreign materials increases infection risk. Indwelling medical devices and prosthetic implants are targets for staphylococcal cell ... ...

Abstract	Staphylococcal species are a leading cause of community- and nosocomial-acquired infections, where the placement of foreign materials increases infection risk. Indwelling medical devices and prosthetic implants are targets for staphylococcal cell adherence and biofilm formation. Biofilm products actively suppress proinflammatory microbicidal responses, as evident by macrophage polarization toward an anti-inflammatory phenotype and the recruitment of myeloid-derived suppressor cells. With the rise in prosthetic hip and knee arthroplasty procedures, together with the recalcitrance of biofilm infections to antibiotic therapy, it is imperative to better understand the mechanism of crosstalk between biofilm-associated bacteria and host immune cells. This review describes the current understanding of how staphylococcal biofilms evade immune-mediated clearance to establish persistent infections. The findings described herein may facilitate the identification of novel treatments for these devastating biofilm-mediated infections.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Arthroplasty, Replacement/adverse effects ; Arthroplasty, Replacement, Hip/adverse effects ; Arthroplasty, Replacement, Knee/adverse effects ; Biofilms/growth & development ; Humans ; Immunity, Cellular ; Prosthesis-Related Infections/immunology ; Prosthesis-Related Infections/microbiology ; Staphylococcal Infections/etiology ; Staphylococcal Infections/immunology ; Staphylococcal Infections/prevention & control
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1200524-1
ISSN	1940-5480 ; 1067-151X
ISSN (online)	1940-5480
ISSN	1067-151X
DOI	10.5435/JAAOS-D-16-00636
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Zs.A 4048: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 274: Show issues

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Article ; Online: Intravital Multiphoton Examination of Implant-Associated

Gries, Casey M / Rivas, Zuivanna / Chen, Justin / Lo, David D

Frontiers in cellular and infection microbiology

2020 Volume 10, Page(s) 574092

Abstract: Bacterial infections associated with implanted medical devices represents a healthcare crisis due to their persistence, antibiotic tolerance, and immune avoidance. Indwelling devices are rapidly coated with host plasma and extracellular matrix proteins ... ...

Abstract	Bacterial infections associated with implanted medical devices represents a healthcare crisis due to their persistence, antibiotic tolerance, and immune avoidance. Indwelling devices are rapidly coated with host plasma and extracellular matrix proteins which can then be exploited by bacterial pathogens for adherence and subsequent biofilm development. Our understanding of the host-pathogen interface that determines the fate of biofilm-mediated infections is limited to the experimental models employed by laboratories studying these organisms. Current
MeSH term(s)	Animals ; Anti-Bacterial Agents ; Biofilms ; Mice ; Prostheses and Implants ; Staphylococcal Infections ; Staphylococcus aureus
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2020-10-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2020.574092
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Article ; Online: Staphylococcus aureus Fibronectin Binding Protein A Mediates Biofilm Development and Infection.

Gries, Casey M / Biddle, Trevor / Bose, Jeffrey L / Kielian, Tammy / Lo, David D

Infection and immunity

2020 Volume 88, Issue 5

Abstract: Implanted medical device-associated infections pose significant health risks, as they are often the result of bacterial biofilm formation. ...

Abstract	Implanted medical device-associated infections pose significant health risks, as they are often the result of bacterial biofilm formation.
MeSH term(s)	Adhesins, Bacterial/metabolism ; Animals ; Bacterial Adhesion/physiology ; Bacterial Proteins/metabolism ; Biofilms/growth & development ; Humans ; Mice ; Mice, Inbred C57BL ; Protein Binding/physiology ; Staphylococcal Infections/metabolism ; Staphylococcal Infections/microbiology ; Staphylococcus aureus/metabolism ; Staphylococcus aureus/pathogenicity
Chemical Substances	Adhesins, Bacterial ; Bacterial Proteins ; fibronectin-binding proteins, bacterial
Language	English
Publishing date	2020-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00859-19
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Zs.A 684: Show issues

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Article ; Online: Crosslinked flagella as a stabilized vaccine adjuvant scaffold.

Gries, Casey M / Mohan, Rohith R / Morikis, Dimitrios / Lo, David D

BMC biotechnology

2019 Volume 19, Issue 1, Page(s) 48

Abstract: Background: Engineered vaccine proteins incorporating both antigen and adjuvant components are constructed with the aim of combining functions to induce effective protective immunity. Bacterial flagellin is a strong candidate for an engineered vaccine ... ...

Abstract	Background: Engineered vaccine proteins incorporating both antigen and adjuvant components are constructed with the aim of combining functions to induce effective protective immunity. Bacterial flagellin is a strong candidate for an engineered vaccine scaffold as it is known to provide adjuvant activity through its TLR5 and inflammasome activation. Moreover, polymerized flagellin filaments can elicit a more robust immunoglobulin response than monomeric flagellin, and the multimeric antigen form can also promote T cell-independent antibody responses. Here, we aim to produce and test a covalently stabilized polymerized flagellar filament, providing additional immune efficacy through stabilization of its polymeric filament structure, as well as stabilization for long-term storage. Results: Computational modeling of monomer packing in flagellin filaments helped identify amino acids with proximity to neighboring flagella protofilaments. Paired cysteine substitutions were made at amino acids predicted to form inter-monomer disulfide cross-links, and these substitutions were capable of forming flagella when transfected into a flagellin-negative strain of Salmonella enterica subspecies Typhimurium. Interestingly, each paired substitution stabilized different helical conformational polymorphisms; the stabilized filaments lost the ability to transition between conformations, reducing bacterial motility. More importantly, the paired substitutions enabled extensive disulfide cross links and intra-filament multimer formation, and in one of the three variants, permitted filament stability in high acidic and temperature conditions where wild-type filaments would normally rapidly depolymerize. In addition, with regard to potential adjuvant activity, all crosslinked flagella filaments were able to induce wild-type levels of epithelial NF-κB in a cell reporter system. Finally, bacterial virulence was unimpaired in epithelial adherence and invasion, and the cysteine substitutions also appeared to increase bacterial resistance to oxidizing and reducing conditions. Conclusions: We identified amino acid pairs, with cysteine substitutions, were able to form intermolecular disulfide bonds that stabilized the resulting flagellar filaments in detergent, hydrochloric acid, and high temperatures while retaining its immunostimulatory function. Flagellar filaments with disulfide-stabilized protofilaments introduce new possibilities for the application of flagella as a vaccine adjuvant. Specifically, increased stability and heat tolerance permits long-term storage in a range of temperature environments, as well as delivery under a range of clinical conditions.
MeSH term(s)	Bacterial Proteins/chemistry ; Bacterial Proteins/immunology ; Bacterial Proteins/metabolism ; Bacterial Vaccines/immunology ; Cross-Linking Reagents/chemistry ; Disulfides ; Flagella/chemistry ; Flagella/metabolism ; Flagellin/chemistry ; Flagellin/immunology ; Flagellin/metabolism ; Models, Molecular ; Protein Conformation ; Protein Multimerization ; Salmonella typhimurium/chemistry ; Salmonella typhimurium/genetics ; Salmonella typhimurium/metabolism
Chemical Substances	Bacterial Proteins ; Bacterial Vaccines ; Cross-Linking Reagents ; Disulfides ; Flagellin (12777-81-0)
Language	English
Publishing date	2019-07-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1472-6750
ISSN (online)	1472-6750
DOI	10.1186/s12896-019-0545-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Crosslinked flagella as a stabilized vaccine adjuvant scaffold

Gries, Casey M / Mohan, Rohith R / Morikis, Dimitrios / Lo, David D

BMC biotechnology. 2019 Dec., v. 19, no. 1

2019

Abstract: BACKGROUND: Engineered vaccine proteins incorporating both antigen and adjuvant components are constructed with the aim of combining functions to induce effective protective immunity. Bacterial flagellin is a strong candidate for an engineered vaccine ... ...

Abstract	BACKGROUND: Engineered vaccine proteins incorporating both antigen and adjuvant components are constructed with the aim of combining functions to induce effective protective immunity. Bacterial flagellin is a strong candidate for an engineered vaccine scaffold as it is known to provide adjuvant activity through its TLR5 and inflammasome activation. Moreover, polymerized flagellin filaments can elicit a more robust immunoglobulin response than monomeric flagellin, and the multimeric antigen form can also promote T cell-independent antibody responses. Here, we aim to produce and test a covalently stabilized polymerized flagellar filament, providing additional immune efficacy through stabilization of its polymeric filament structure, as well as stabilization for long-term storage. RESULTS: Computational modeling of monomer packing in flagellin filaments helped identify amino acids with proximity to neighboring flagella protofilaments. Paired cysteine substitutions were made at amino acids predicted to form inter-monomer disulfide cross-links, and these substitutions were capable of forming flagella when transfected into a flagellin-negative strain of Salmonella enterica subspecies Typhimurium. Interestingly, each paired substitution stabilized different helical conformational polymorphisms; the stabilized filaments lost the ability to transition between conformations, reducing bacterial motility. More importantly, the paired substitutions enabled extensive disulfide cross links and intra-filament multimer formation, and in one of the three variants, permitted filament stability in high acidic and temperature conditions where wild-type filaments would normally rapidly depolymerize. In addition, with regard to potential adjuvant activity, all crosslinked flagella filaments were able to induce wild-type levels of epithelial NF-κB in a cell reporter system. Finally, bacterial virulence was unimpaired in epithelial adherence and invasion, and the cysteine substitutions also appeared to increase bacterial resistance to oxidizing and reducing conditions. CONCLUSIONS: We identified amino acid pairs, with cysteine substitutions, were able to form intermolecular disulfide bonds that stabilized the resulting flagellar filaments in detergent, hydrochloric acid, and high temperatures while retaining its immunostimulatory function. Flagellar filaments with disulfide-stabilized protofilaments introduce new possibilities for the application of flagella as a vaccine adjuvant. Specifically, increased stability and heat tolerance permits long-term storage in a range of temperature environments, as well as delivery under a range of clinical conditions.
Keywords	Salmonella enterica ; Toll-like receptor 5 ; antibody formation ; antigens ; bacterial motility ; crosslinking ; cysteine ; detergents ; disulfide bonds ; disulfides ; epithelium ; flagellin ; flagellum ; heat tolerance ; hydrochloric acid ; immunoglobulins ; immunostimulants ; inflammasomes ; models ; polymerization ; polymers ; storage time ; temperature ; transcription factor NF-kappa B ; vaccine adjuvants ; vaccines ; virulence
Language	English
Dates of publication	2019-12
Size	p. 48.
Publishing place	BioMed Central
Document type	Article
ISSN	1472-6750
DOI	10.1186/s12896-019-0545-3
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: SaeRS Is Responsive to Cellular Respiratory Status and Regulates Fermentative Biofilm Formation in Staphylococcus aureus.

Mashruwala, Ameya A / Gries, Casey M / Scherr, Tyler D / Kielian, Tammy / Boyd, Jeffrey M

Infection and immunity

2017 Volume 85, Issue 8

Abstract: Biofilms are multicellular communities of microorganisms living as a quorum rather than as individual cells. The bacterial human ... ...

Abstract	Biofilms are multicellular communities of microorganisms living as a quorum rather than as individual cells. The bacterial human pathogen
MeSH term(s)	Adhesins, Bacterial/genetics ; Adhesins, Bacterial/metabolism ; Bacterial Adhesion ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Biofilms/growth & development ; Fermentation ; Gene Expression Regulation, Bacterial ; N-Acetylmuramoyl-L-alanine Amidase/genetics ; N-Acetylmuramoyl-L-alanine Amidase/metabolism ; Oxygen/metabolism ; Phenotype ; Phosphorylation ; Protein Kinases/metabolism ; Staphylococcus aureus/genetics ; Staphylococcus aureus/metabolism ; Staphylococcus aureus/physiology ; Teichoic Acids/metabolism ; Transcription Factors
Chemical Substances	Adhesins, Bacterial ; Bacterial Proteins ; SaeR protein, Staphylococcus aureus ; Teichoic Acids ; Transcription Factors ; fibronectin-binding proteins, bacterial ; Protein Kinases (EC 2.7.-) ; SaeS protein, Staphylococcus aureus (EC 2.7.3.-) ; N-Acetylmuramoyl-L-alanine Amidase (EC 3.5.1.28) ; Oxygen (S88TT14065)
Language	English
Publishing date	2017-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00157-17
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Article ; Online: Arginase-1 Expression in Myeloid Cells Regulates Staphylococcus aureus Planktonic but Not Biofilm Infection.

Yamada, Kelsey J / Heim, Cortney E / Aldrich, Amy L / Gries, Casey M / Staudacher, Anna G / Kielian, Tammy

Infection and immunity

2018 Volume 86, Issue 7

Abstract: Staphylococcus ... ...

Abstract	Staphylococcus aureus
MeSH term(s)	Animals ; Arginase/physiology ; Biofilms ; Biogenic Polyamines/physiology ; Catheter-Related Infections ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/physiology ; Nitric Oxide Synthase Type II/analysis ; Plankton/microbiology ; Staphylococcal Infections/etiology ; Staphylococcus aureus/physiology
Chemical Substances	Biogenic Polyamines ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nos2 protein, mouse (EC 1.14.13.39) ; Arg1 protein, mouse (EC 3.5.3.1) ; Arginase (EC 3.5.3.1)
Language	English
Publishing date	2018-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00206-18
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Article ; Online: Lactate production by Staphylococcus aureus biofilm inhibits HDAC11 to reprogramme the host immune response during persistent infection.

Heim, Cortney E / Bosch, Megan E / Yamada, Kelsey J / Aldrich, Amy L / Chaudhari, Sujata S / Klinkebiel, David / Gries, Casey M / Alqarzaee, Abdulelah A / Li, Yixuan / Thomas, Vinai C / Seto, Edward / Karpf, Adam R / Kielian, Tammy

Nature microbiology

2020 Volume 5, Issue 10, Page(s) 1271–1284

Abstract: Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI), resulting in considerable disability and prolonged treatment. It is known that host leukocyte IL-10 production is required for S. aureus biofilm persistence ... ...

Abstract	Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI), resulting in considerable disability and prolonged treatment. It is known that host leukocyte IL-10 production is required for S. aureus biofilm persistence in PJI. An S. aureus bursa aurealis Tn library consisting of 1,952 non-essential genes was screened for mutants that failed to induce IL-10 in myeloid-derived suppressor cells (MDSCs), which identified a critical role for bacterial lactic acid biosynthesis. We generated an S. aureus ddh/ldh1/ldh2 triple Tn mutant that cannot produce D- or L-lactate. Co-culture of MDSCs or macrophages with ddh/ldh1/ldh2 mutant biofilm produced substantially less IL-10 compared with wild-type S. aureus, which was also observed in a mouse model of PJI and led to reduced biofilm burden. Using MDSCs recovered from the mouse PJI model and in vitro leukocyte-biofilm co-cultures, we show that bacterial-derived lactate inhibits histone deacetylase 11, causing unchecked HDAC6 activity and increased histone 3 acetylation at the Il-10 promoter, resulting in enhanced Il-10 transcription in MDSCs and macrophages. Finally, we show that synovial fluid of patients with PJI contains elevated amounts of D-lactate and IL-10 compared with control subjects, and bacterial lactate increases IL-10 production by human monocyte-derived macrophages.
MeSH term(s)	Biofilms ; Biomarkers ; Biosynthetic Pathways ; Cytokines/metabolism ; Histone Deacetylases/metabolism ; Host-Pathogen Interactions/immunology ; Inflammation Mediators/metabolism ; Lactic Acid/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/metabolism ; Staphylococcal Infections/immunology ; Staphylococcal Infections/metabolism ; Staphylococcal Infections/microbiology ; Staphylococcus aureus/physiology
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators ; Lactic Acid (33X04XA5AT) ; HDAC11 protein, human (EC 3.5.1.98) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2020-07-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-020-0756-3
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