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Article ; Online: Nonconformity of biofilm formation in vivo and in vitro based on Staphylococcus aureus accessory gene regulator status.

Jordan, S Caroline / Hall, Pamela R / Daly, Seth M

2022 Volume 12, Issue 1, Page(s) 1251

Abstract: Staphylococcus aureus is an opportunistic, pathogenic bacteria that causes significant morbidity and mortality. As antibiotic resistance by S. aureus continues to be a serious concern, developing novel drug therapies to combat these infections is vital. ... ...

Abstract	Staphylococcus aureus is an opportunistic, pathogenic bacteria that causes significant morbidity and mortality. As antibiotic resistance by S. aureus continues to be a serious concern, developing novel drug therapies to combat these infections is vital. Quorum sensing inhibitors (QSI) dampen S. aureus virulence and facilitate clearance by the host immune system by blocking quorum sensing signaling that promotes upregulation of virulence genes controlled by the accessory gene regulator (agr) operon. While QSIs have shown therapeutic promise in mouse models of S. aureus skin infection, their further development has been hampered by the suggestion that agr inhibition promotes biofilm formation. In these studies, we investigated the relationship between agr function and biofilm growth across various S. aureus strains and experimental conditions, including in a mouse model of implant-associated infection. We found that agr deletion was associated with the presence of increased biofilm only under narrow in vitro conditions and, crucially, was not associated with enhanced biofilm development or enhanced morbidity in vivo.
MeSH term(s)	Animals ; Bacterial Proteins/physiology ; Biofilms/growth & development ; Culture Techniques ; Female ; Mice, Inbred BALB C ; Quorum Sensing ; Staphylococcus aureus/physiology ; Trans-Activators/physiology ; Mice
Chemical Substances	Agr protein, Staphylococcus aureus ; Bacterial Proteins ; Trans-Activators
Language	English
Publishing date	2022-01-24
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-05382-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Nonconformity of biofilm formation in vivo and in vitro based on Staphylococcus aureus accessory gene regulator status

S. Caroline Jordan / Pamela R. Hall / Seth M. Daly

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 11

Abstract: Abstract Staphylococcus aureus is an opportunistic, pathogenic bacteria that causes significant morbidity and mortality. As antibiotic resistance by S. aureus continues to be a serious concern, developing novel drug therapies to combat these infections ... ...

Abstract	Abstract Staphylococcus aureus is an opportunistic, pathogenic bacteria that causes significant morbidity and mortality. As antibiotic resistance by S. aureus continues to be a serious concern, developing novel drug therapies to combat these infections is vital. Quorum sensing inhibitors (QSI) dampen S. aureus virulence and facilitate clearance by the host immune system by blocking quorum sensing signaling that promotes upregulation of virulence genes controlled by the accessory gene regulator (agr) operon. While QSIs have shown therapeutic promise in mouse models of S. aureus skin infection, their further development has been hampered by the suggestion that agr inhibition promotes biofilm formation. In these studies, we investigated the relationship between agr function and biofilm growth across various S. aureus strains and experimental conditions, including in a mouse model of implant-associated infection. We found that agr deletion was associated with the presence of increased biofilm only under narrow in vitro conditions and, crucially, was not associated with enhanced biofilm development or enhanced morbidity in vivo.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Quantitative Hemolysis Assays.

Ridder, Miranda J / Daly, Seth M / Hall, Pamela R / Bose, Jeffrey L

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2341, Page(s) 25–30

Abstract: Many strains of Staphylococcus aureus produce a variety of cytolysins that target many different cell types to both fight the immune system and acquire nutrients. This includes hemolysins which destroy erythrocytes and are well studied virulence factors. ...

Abstract	Many strains of Staphylococcus aureus produce a variety of cytolysins that target many different cell types to both fight the immune system and acquire nutrients. This includes hemolysins which destroy erythrocytes and are well studied virulence factors. Traditionally, hemolysin activity is measured on blood agar plates due to the simplicity of the assay. While this is telling, it cannot encapsulate the full story because S. aureus is known to behave differently in broth and on agar. Furthermore, plate-based assays are primarily semiquantitative and often a more accurate determination of hemolytic potential is needed to discern differences between strains. Here, we describe a method to quantify hemolysin activity from broth or similarly grown cells.
MeSH term(s)	Animals ; Bacterial Proteins/analysis ; Bacterial Proteins/metabolism ; Culture Media/chemistry ; Erythrocytes/physiology ; Hemolysin Proteins/analysis ; Hemolysin Proteins/metabolism ; Hemolysis ; Humans ; Staphylococcus aureus/growth & development ; Staphylococcus aureus/metabolism ; Staphylococcus aureus/pathogenicity ; Virulence Factors/analysis ; Virulence Factors/metabolism
Chemical Substances	Bacterial Proteins ; Culture Media ; Hemolysin Proteins ; Virulence Factors
Language	English
Publishing date	2021-07-15
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1550-8_4
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Article ; Online: Clock-Drawing Test as a Screening Tool for Cognitive Impairment Associated With Fecal Immunochemical Test Collection Errors.

Daly, Jeanette M / Xu, Yinghui / Crockett, Seth D / Schmidt, Megan E / Kim, Peter / Levy, Barcey T

Annals of family medicine

2022 Volume 20, Issue 5, Page(s) 452–459

Abstract: Purpose: The purposes of this study were to determine if (1) certain demographic characteristics (potential predictors) of participants, and (2) clock-drawing test results (as a screening test for cognitive impairment) were associated with fecal ... ...

Abstract	Purpose: The purposes of this study were to determine if (1) certain demographic characteristics (potential predictors) of participants, and (2) clock-drawing test results (as a screening test for cognitive impairment) were associated with fecal immunochemical test (FIT) sample collection errors. Methods: Patients scheduled for an upcoming colonoscopy were asked to collect stool samples using 5 different FITs. Patients completed a questionnaire that included the clock-drawing test. Errors included mistakes or omissions in recording the stool collection date and errors in stool collection. Each clock drawing was scored by 2 reviewers using 2 established methods. Results: Of the 1,448 participants with a clock drawing, 63% were female with a mean age of 63 years. In this population there were 83% White, 6% Black, and 24% Hispanic persons. Cognitive impairment was found in 292 patients by the Mendes-Santos method. Kappa coefficient for the 2 clock-drawing scores was 0.79 (P <.001). The multivariable generalized linear mixed model for FIT collection errors indicated being female (adjusted odds ratio [AOR], 1.64; 95% CI, 1.09-2.48), having an 8th grade or less education (AOR, 3.40; 95% CI, 1.87-6.18), and having an abnormal Mendes-Santos method clock score (AOR, 1.65; 95% CI, 1.08-2.54) were associated with significantly more errors. Conclusion: Among the participants who do not have dementia, FIT collection errors were made not only by those who had abnormal clock drawing, but also, by those with normal clock drawings. Subjects being female, having 8th grade education or less, and having an abnormal clock drawing scored by Mendes-Santos's method were associated with FIT collection errors.
MeSH term(s)	Cognitive Dysfunction/diagnosis ; Colonoscopy ; Colorectal Neoplasms/diagnosis ; Early Detection of Cancer ; Feces ; Female ; Humans ; Male ; Mass Screening/methods ; Middle Aged ; Neuropsychological Tests
Language	English
Publishing date	2022-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2171425-3
ISSN	1544-1717 ; 1544-1709
ISSN (online)	1544-1717
ISSN	1544-1709
DOI	10.1370/afm.2855
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Article ; Online: Inhibition of Bacterial Growth by Peptide-Conjugated Morpholino Oligomers.

Daly, Seth M / Sturge, Carolyn R / Greenberg, David E

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1565, Page(s) 115–122

Abstract: Morpholino oligomers (MOs) are antisense molecules designed for sequence-specific binding of target mRNA. In bacteria, inhibition is hypothesized to occur by preventing translation initiation. Cell-penetrating peptides may be conjugated to the 5'- or 3'- ... ...

Abstract	Morpholino oligomers (MOs) are antisense molecules designed for sequence-specific binding of target mRNA. In bacteria, inhibition is hypothesized to occur by preventing translation initiation. Cell-penetrating peptides may be conjugated to the 5'- or 3'-termini of an MO to enhance cellular entry and therefore inhibition. Here we describe the three standard microbiological assays to assess in vitro antibacterial MO efficacy.
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-6817-6_10
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Article ; Online: Impact of a warm anomaly in the Pacific Arctic region derived from time-series export fluxes.

Lalande, Catherine / Grebmeier, Jacqueline M / McDonnell, Andrew M P / Hopcroft, Russell R / O'Daly, Stephanie / Danielson, Seth L

PloS one

2021 Volume 16, Issue 8, Page(s) e0255837

Abstract: Unusually warm conditions recently observed in the Pacific Arctic region included a dramatic loss of sea ice cover and an enhanced inflow of warmer Pacific-derived waters. Moored sediment traps deployed at three biological hotspots of the Distributed ... ...

Abstract	Unusually warm conditions recently observed in the Pacific Arctic region included a dramatic loss of sea ice cover and an enhanced inflow of warmer Pacific-derived waters. Moored sediment traps deployed at three biological hotspots of the Distributed Biological Observatory (DBO) during this anomalously warm period collected sinking particles nearly continuously from June 2017 to July 2019 in the northern Bering Sea (DBO2) and in the southern Chukchi Sea (DBO3), and from August 2018 to July 2019 in the northern Chukchi Sea (DBO4). Fluxes of living algal cells, chlorophyll a (chl a), total particulate matter (TPM), particulate organic carbon (POC), and zooplankton fecal pellets, along with zooplankton and meroplankton collected in the traps, were used to evaluate spatial and temporal variations in the development and composition of the phytoplankton and zooplankton communities in relation to sea ice cover and water temperature. The unprecedented sea ice loss of 2018 in the northern Bering Sea led to the export of a large bloom dominated by the exclusively pelagic diatoms Chaetoceros spp. at DBO2. Despite this intense bloom, early sea ice breakup resulted in shorter periods of enhanced chl a and diatom fluxes at all DBO sites, suggesting a weaker biological pump under reduced ice cover in the Pacific Arctic region, while the coincident increase or decrease in TPM and POC fluxes likely reflected variations in resuspension events. Meanwhile, the highest transport of warm Pacific waters during 2017-2018 led to a dominance of the small copepods Pseudocalanus at all sites. Whereas the export of ice-associated diatoms during 2019 suggested a return to more typical conditions in the northern Bering Sea, the impact on copepods persisted under the continuously enhanced transport of warm Pacific waters. Regardless, the biological pump remained strong on the shallow Pacific Arctic shelves.
MeSH term(s)	Animals ; Arctic Regions ; Carbon Cycle ; Chlorophyll A/analysis ; Copepoda/growth & development ; Copepoda/metabolism ; Diatoms/growth & development ; Diatoms/metabolism ; Ecosystem ; Ice Cover ; Phytoplankton/growth & development ; Phytoplankton/metabolism ; Temperature ; Zooplankton/growth & development ; Zooplankton/metabolism
Chemical Substances	Chlorophyll A (YF5Q9EJC8Y)
Language	English
Publishing date	2021-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0255837
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Article ; Online: The teammate trial: Study design and rationale tacrolimus and everolimus against tacrolimus and MMF in pediatric heart transplantation using the major adverse transplant event (MATE) score.

Almond, Christopher S / Sleeper, Lynn A / Rossano, Joseph W / Bock, Matthew J / Pahl, Elfriede / Auerbach, Scott / Lal, Ashwin / Hollander, Seth A / Miyamoto, Shelley D / Castleberry, Chesney / Lee, Joanne / Barkoff, Lynsey M / Gonzales, Selena / Klein, Gloria / Daly, Kevin P

American heart journal

2023 Volume 260, Page(s) 100–112

Abstract: Background: Currently there are no immunosuppression regimens FDA-approved to prevent rejection in pediatric heart transplantation (HT). In recent years, everolimus (EVL) has emerged as a potential alternative to standard tacrolimus (TAC) as the primary ...

Abstract	Background: Currently there are no immunosuppression regimens FDA-approved to prevent rejection in pediatric heart transplantation (HT). In recent years, everolimus (EVL) has emerged as a potential alternative to standard tacrolimus (TAC) as the primary immunosuppressant to prevent rejection that may also reduce the risk of cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD) and cytomegalovirus (CMV) infection. However, the 2 regimens have never been compared head-to-head in a randomized trial. The study design and rationale are reviewed in light of the challenges inherent in rare disease research. Methods: The TEAMMATE trial (IND 127980) is the first multicenter randomized clinical trial (RCT) in pediatric HT. The primary purpose is to evaluate the safety and efficacy of EVL and low-dose TAC (LD-TAC) compared to standard-dose TAC and mycophenolate mofetil (MMF). Children aged <21 years at HT were randomized (1:1 ratio) at 6 months post-HT to either regimen, and followed for 30 months. Children with recurrent rejection, multi-organ transplant recipients, and those with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m Conclusion: The TEAMMATE trial is the first multicenter RCT in pediatric HT. It is anticipated that the study will provide important information about the safety and efficacy of everolimus vs tacrolimus-based regimens and will provide valuable lessons into the design and conduct of future trials in pediatric HT.
MeSH term(s)	Humans ; Child ; Tacrolimus/therapeutic use ; Tacrolimus/pharmacology ; Everolimus/pharmacology ; Mycophenolic Acid/therapeutic use ; Mycophenolic Acid/pharmacology ; Kidney Transplantation/adverse effects ; Immunosuppressive Agents/therapeutic use ; Immunosuppressive Agents/pharmacology ; Heart Transplantation ; Renal Insufficiency, Chronic/etiology ; Heart Diseases/etiology ; Drug Therapy, Combination ; Graft Survival
Chemical Substances	Tacrolimus (WM0HAQ4WNM) ; Everolimus (9HW64Q8G6G) ; Mycophenolic Acid (HU9DX48N0T) ; Immunosuppressive Agents
Language	English
Publishing date	2023-02-23
Publishing country	United States
Document type	Randomized Controlled Trial ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80026-0
ISSN	1097-6744 ; 0002-8703
ISSN (online)	1097-6744
ISSN	0002-8703
DOI	10.1016/j.ahj.2023.02.002
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Article ; Online: Complement Receptor 3 Contributes to the Sexual Dimorphism in Neutrophil Killing of

Pokhrel, Srijana / Triplett, Kathleen D / Daly, Seth M / Joyner, Jason A / Sharma, Geetanjali / Hathaway, Helen J / Prossnitz, Eric R / Hall, Pamela R

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 205, Issue 6, Page(s) 1593–1600

Abstract: We previously reported sex differences in innate susceptibility ... ...

Abstract	We previously reported sex differences in innate susceptibility to
MeSH term(s)	Animals ; Antibodies, Blocking/metabolism ; CD11b Antigen/immunology ; CD11b Antigen/metabolism ; Complement C3/metabolism ; Cytotoxicity, Immunologic ; Female ; Host-Pathogen Interactions ; Humans ; Macrophage-1 Antigen/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neutrophils/physiology ; Reactive Oxygen Species/metabolism ; Sex Characteristics ; Sex Factors ; Staphylococcal Infections/immunology ; Staphylococcus aureus/physiology
Chemical Substances	Antibodies, Blocking ; CD11b Antigen ; Complement C3 ; Macrophage-1 Antigen ; Reactive Oxygen Species
Language	English
Publishing date	2020-08-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2000545
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Article ; Online: Impact of a warm anomaly in the Pacific Arctic region derived from time-series export fluxes.

Catherine Lalande / Jacqueline M Grebmeier / Andrew M P McDonnell / Russell R Hopcroft / Stephanie O'Daly / Seth L Danielson

PLoS ONE, Vol 16, Iss 8, p e

2021 Volume 0255837

Abstract	Unusually warm conditions recently observed in the Pacific Arctic region included a dramatic loss of sea ice cover and an enhanced inflow of warmer Pacific-derived waters. Moored sediment traps deployed at three biological hotspots of the Distributed Biological Observatory (DBO) during this anomalously warm period collected sinking particles nearly continuously from June 2017 to July 2019 in the northern Bering Sea (DBO2) and in the southern Chukchi Sea (DBO3), and from August 2018 to July 2019 in the northern Chukchi Sea (DBO4). Fluxes of living algal cells, chlorophyll a (chl a), total particulate matter (TPM), particulate organic carbon (POC), and zooplankton fecal pellets, along with zooplankton and meroplankton collected in the traps, were used to evaluate spatial and temporal variations in the development and composition of the phytoplankton and zooplankton communities in relation to sea ice cover and water temperature. The unprecedented sea ice loss of 2018 in the northern Bering Sea led to the export of a large bloom dominated by the exclusively pelagic diatoms Chaetoceros spp. at DBO2. Despite this intense bloom, early sea ice breakup resulted in shorter periods of enhanced chl a and diatom fluxes at all DBO sites, suggesting a weaker biological pump under reduced ice cover in the Pacific Arctic region, while the coincident increase or decrease in TPM and POC fluxes likely reflected variations in resuspension events. Meanwhile, the highest transport of warm Pacific waters during 2017-2018 led to a dominance of the small copepods Pseudocalanus at all sites. Whereas the export of ice-associated diatoms during 2019 suggested a return to more typical conditions in the northern Bering Sea, the impact on copepods persisted under the continuously enhanced transport of warm Pacific waters. Regardless, the biological pump remained strong on the shallow Pacific Arctic shelves.
Keywords	Medicine ; R ; Science ; Q
Subject code	551 ; 550
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Staphylococcus aureus Fatty Acid Kinase FakA Modulates Pathogenesis during Skin Infection via Proteases.

Ridder, Miranda J / Daly, Seth M / Triplett, Kathleen D / Seawell, Nichole A / Hall, Pamela R / Bose, Jeffrey L

Infection and immunity

2020 Volume 88, Issue 8

Abstract: Staphylococcus ... ...

Abstract	Staphylococcus aureus
MeSH term(s)	Animals ; Bacterial Load ; Bacterial Proteins/genetics ; Bacterial Proteins/immunology ; Bacterial Toxins/genetics ; Bacterial Toxins/immunology ; Chemokine CCL4/genetics ; Chemokine CCL4/immunology ; Female ; Gene Expression Regulation ; Hemolysin Proteins/genetics ; Hemolysin Proteins/immunology ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Interleukin-17/genetics ; Interleukin-17/immunology ; Interleukin-1alpha/genetics ; Interleukin-1alpha/immunology ; Interleukin-1beta/genetics ; Interleukin-1beta/immunology ; Interleukin-6/genetics ; Interleukin-6/immunology ; Metalloendopeptidases/deficiency ; Metalloendopeptidases/genetics ; Metalloendopeptidases/immunology ; Mice ; Phosphotransferases (Carboxyl Group Acceptor)/deficiency ; Phosphotransferases (Carboxyl Group Acceptor)/genetics ; Phosphotransferases (Carboxyl Group Acceptor)/immunology ; Serine Endopeptidases/deficiency ; Serine Endopeptidases/genetics ; Serine Endopeptidases/immunology ; Signal Transduction ; Skin/immunology ; Skin/microbiology ; Skin/pathology ; Skin Ulcer/genetics ; Skin Ulcer/immunology ; Skin Ulcer/microbiology ; Skin Ulcer/pathology ; Staphylococcal Skin Infections/genetics ; Staphylococcal Skin Infections/immunology ; Staphylococcal Skin Infections/microbiology ; Staphylococcal Skin Infections/pathology ; Staphylococcus aureus/enzymology ; Staphylococcus aureus/genetics ; Staphylococcus aureus/immunology ; Staphylococcus aureus/pathogenicity ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/immunology ; Virulence Factors/genetics ; Virulence Factors/immunology
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; Ccl4 protein, mouse ; Chemokine CCL4 ; Hemolysin Proteins ; IL1B protein, mouse ; Il17a protein, mouse ; Il1a protein, mouse ; Interleukin-17 ; Interleukin-1alpha ; Interleukin-1beta ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Virulence Factors ; interleukin-6, mouse ; staphylococcal alpha-toxin ; Phosphotransferases (Carboxyl Group Acceptor) (EC 2.7.2.-) ; branched-chain fatty-acid-kinase (EC 2.7.2.14) ; Serine Endopeptidases (EC 3.4.21.-) ; sspB protein, Staphylococcus aureus (EC 3.4.21.-) ; glutamyl endopeptidase (EC 3.4.21.19) ; Metalloendopeptidases (EC 3.4.24.-) ; auR protein, Staphylococcus aureus (EC 3.4.24.29)
Language	English
Publishing date	2020-07-21
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.00163-20
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