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1.
Dent Clin North Am ; 67(4): 687-690, 2023 10.
Article in English | MEDLINE | ID: mdl-37714625

ABSTRACT

Herpes zoster (HZ) is an acute and painful neurocutaneous infection caused by the reactivation of a latent varicella-zoster virus in the dorsal root or cranial nerve ganglia. It is characterized by 3 stages: prodromal, acute, and chronic. During the prodromal stage, reactivation in the maxillary branch of the trigeminal nerve closely mimics odontalgia, and HZ should be in the differential diagnosis. Patients with HZ develop painful lesions following the affected dermatome. Laboratory testing confirms the diagnosis; treatment is with antiviral agents. Early detection and treatment shorten the course of the infection and lessen the severity of the associated postherpetic neuralgia.


Subject(s)
Herpes Zoster , Neuralgia, Postherpetic , Humans , Herpesvirus 3, Human , Toothache/diagnosis , Toothache/etiology , Herpes Zoster/complications , Herpes Zoster/diagnosis , Herpes Zoster/drug therapy , Trigeminal Nerve , Neuralgia, Postherpetic/diagnosis
2.
mBio ; 14(5): e0135023, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37737591

ABSTRACT

IMPORTANCE: During infection, bacteria must overcome the dual threats of metal starvation and intoxication. This work reveals that the zinc-withholding response of the host sensitizes S. aureus to copper intoxication. In response to zinc starvation, S. aureus utilizes the metallophore staphylopine. The current work revealed that the host can leverage the promiscuity of staphylopine to intoxicate S. aureus during infection. Significantly, staphylopine-like metallophores are produced by a wide range of pathogens, suggesting that this is a conserved weakness that the host can leverage to toxify invaders with copper. Moreover, it challenges the assumption that the broad-spectrum metal binding of metallophores is inherently beneficial to bacteria.


Subject(s)
Copper , Staphylococcus aureus , Copper/toxicity , Copper/metabolism , Staphylococcus aureus/metabolism , Metals/metabolism , Zinc/metabolism , Bacteria/metabolism
3.
bioRxiv ; 2023 May 31.
Article in English | MEDLINE | ID: mdl-37398167

ABSTRACT

Microorganisms can acquire metal ions in metal-limited environments using small molecules called metallophores. While metals and their importers are essential, metals can also be toxic, and metallophores have limited ability to discriminate metals. The impact of the metallophore-mediated non-cognate metal uptake on bacterial metal homeostasis and pathogenesis remains to be defined. The globally significant pathogen Staphylococcus aureus uses the Cnt system to secrete the metallophore staphylopine in zinc-limited host niches. Here, we show that staphylopine and the Cnt system facilitate bacterial copper uptake, potentiating the need for copper detoxification. During in vivo infection, staphylopine usage increased S. aureus susceptibility to host-mediated copper stress, indicating that the innate immune response can harness the antimicrobial potential of altered elemental abundances in host niches. Collectively, these observations show that while the broad-spectrum metal-chelating properties of metallophores can be advantageous, the host can exploit these properties to drive metal intoxication and mediate antibacterial control. IMPORTANCE: During infection bacteria must overcome the dual threats of metal starvation and intoxication. This work reveals that the zinc-withholding response of the host sensitizes Staphylococcus aureus to copper intoxication. In response to zinc starvation S. aureus utilizes the metallophore staphylopine. The current work revealed that the host can leverage the promiscuity of staphylopine to intoxicate S. aureus during infection. Significantly, staphylopine-like metallophores are produced by a wide range of pathogens, suggesting that this is a conserved weakness that the host can leverage to toxify invaders with copper. Moreover, it challenges the assumption that the broad-spectrum metal binding of metallophores is inherently beneficial to bacteria.

4.
mBio ; 14(4): e0030423, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37358277

ABSTRACT

Group B Streptococcus (GBS) is a Gram-positive pathobiont that can cause adverse health outcomes in neonates and vulnerable adult populations. GBS is one of the most frequently isolated bacteria from diabetic (Db) wound infections but is rarely found in the non-diabetic (nDb) wound environment. Previously, RNA sequencing of wound tissue from Db wound infections in leprdb diabetic mice showed increased expression of neutrophil factors, and genes involved in GBS metal transport such as the zinc (Zn), manganese (Mn), and putative nickel (Ni) import systems. Here, we develop a Streptozotocin-induced diabetic wound model to evaluate the pathogenesis of two invasive strains of GBS, serotypes Ia and V. We observe an increase in metal chelators such as calprotectin (CP) and lipocalin-2 during diabetic wound infections compared to nDb. We find that CP limits GBS survival in wounds of non-diabetic mice but does not impact survival in diabetic wounds. Additionally, we utilize GBS metal transporter mutants and determine that the Zn, Mn, and putative Ni transporters in GBS are dispensable in diabetic wound infection but contributed to bacterial persistence in non-diabetic animals. Collectively, these data suggest that in non-diabetic mice, functional nutritional immunity mediated by CP is effective at mitigating GBS infection, whereas in diabetic mice, the presence of CP is not sufficient to control GBS wound persistence. IMPORTANCE Diabetic wound infections are difficult to treat and often become chronic due to an impaired immune response as well as the presence of bacterial species that establish persistent infections. Group B Streptococcus (GBS) is one of the most frequently isolated bacterial species in diabetic wound infections and, as a result, is one of the leading causes of death from skin and subcutaneous infection. However, GBS is notoriously absent in non-diabetic wounds, and little is known about why this species thrives in diabetic infection. The work herein investigates how alterations in diabetic host immunity may contribute to GBS success during diabetic wound infection.


Subject(s)
Diabetes Mellitus, Experimental , Streptococcal Infections , Wound Infection , Mice , Animals , Neutrophils , Streptococcal Infections/microbiology , Streptococcus agalactiae/genetics
5.
Radiat Prot Dosimetry ; 199(8-9): 970-976, 2023 May 24.
Article in English | MEDLINE | ID: mdl-37225193

ABSTRACT

Indoor radon concentrations were surveyed in 230 public schools in four Bulgarian districts for the period November/December 2019 to May/June 2020. The measurements were carried out in 2427 rooms on the basement, ground floor and first floor using the passive track detectors of the Radosys system. The estimated arithmetic and geometric means with standard deviations were 153 ± 154 and 114 Bq/m3 (geometric standard deviation (GSD) = 2.08), respectively. The results are higher than those referred from the National Radon Survey in dwellings. In 9.4% of the rooms, the radon concentrations were above the reference value of 300 Bq/m3. The difference between indoor radon concentrations in the districts was significant, which proves its spatial variation. The hypothesis that the applied energy efficiency measures increase indoor radon values in buildings was confirmed. The surveys demonstrated the importance of indoor radon measurements in school buildings, in order to control and reduce children's exposure.


Subject(s)
Radon , Child , Humans , Bulgaria , Reference Values , Schools
6.
Proc Natl Acad Sci U S A ; 120(11): e2216774120, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36888662

ABSTRACT

Cells regularly experience fluid flow in natural systems. However, most experimental systems rely on batch cell culture and fail to consider the effect of flow-driven dynamics on cell physiology. Using microfluidics and single-cell imaging, we discover that the interplay of physical shear rate (a measure of fluid flow) and chemical stress trigger a transcriptional response in the human pathogen Pseudomonas aeruginosa. In batch cell culture, cells protect themselves by quickly scavenging the ubiquitous chemical stressor hydrogen peroxide (H2O2) from the media. In microfluidic conditions, we observe that cell scavenging generates spatial gradients of H2O2. High shear rates replenish H2O2, abolish gradients, and generate a stress response. Combining mathematical simulations and biophysical experiments, we find that flow triggers an effect like "wind-chill" that sensitizes cells to H2O2 concentrations 100 to 1,000 times lower than traditionally studied in batch cell culture. Surprisingly, the shear rate and H2O2 concentration required to generate a transcriptional response closely match their respective values in the human bloodstream. Thus, our results explain a long-standing discrepancy between H2O2 levels in experimental and host environments. Finally, we demonstrate that the shear rate and H2O2 concentration found in the human bloodstream trigger gene expression in the blood-relevant human pathogen Staphylococcus aureus, suggesting that flow sensitizes bacteria to chemical stress in natural environments.


Subject(s)
Bacteria , Hydrogen Peroxide , Humans , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/metabolism , Bacteria/metabolism , Microfluidics , Batch Cell Culture Techniques , Pseudomonas aeruginosa/genetics
7.
Environ Res ; 221: 115234, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36634896

ABSTRACT

INTRODUCTION: The use of electronic nicotine delivery systems (ENDS), or vaping, is a relatively recent phenomenon, and there are various gaps in our current knowledge regarding the specific effects of e-cigarettes, such as their immunological effects. The importance of this question became even more relevant in light of the COVID-19 pandemic. OBJECTIVE: This literature review examines the relationship between the use of electronic nicotine delivery systems (ENDS) and immunological effects to examine available information and identify gaps in the current knowledge. Our search strategy included studies focusing on the effects of ENDS on the immune response during infectious respiratory diseases such as COVID-19 and pneumonia. METHODS: Peer-reviewed studies presenting quantitative data published from 2007, the year that e-cigarettes were introduced to the US market until 2022 have been included. All studies were indexed in PubMed. We excluded papers on THC and EVALI (E-cigarette, or Vaping Product, Use Associated Lung Injury) as we wanted to focus on the effects of nicotine devices. RESULTS: Among the 21 articles that assessed the relationship between ENDS and immunological health effects, we found eight studies based on cell models, two articles based on both cell and mouse models, five articles based on mouse models, and six studies of human populations. Most of the articles identified in our review demonstrated a potential association between vaping and adverse immunological health effects. DISCUSSION: Overall, the evidence from the cell and animal studies indicates that there is a positive, statistically significant association between vaping and adverse immune response during infectious respiratory diseases. The evidence from human studies is not conclusive.


Subject(s)
COVID-19 , Electronic Nicotine Delivery Systems , Vaping , Animals , Mice , Humans , Pandemics , Lung , Nicotine , Vaping/adverse effects
8.
mBio ; 14(1): e0322322, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36598285

ABSTRACT

The preferred carbon source of Staphylococcus aureus and many other pathogens is glucose, and its consumption is critical during infection. However, glucose utilization increases the cellular demand for manganese, a nutrient sequestered by the host as a defense against invading pathogens. Therefore, bacteria must balance glucose metabolism with the increasing demand that metal-dependent processes, such as glycolysis, impose upon the cell. A critical regulator that enables S. aureus to resist nutritional immunity is the ArlRS two-component system. This work revealed that ArlRS regulates the expression of FdaB, a metal-independent fructose 1,6-bisphosphate aldolase. Further investigation revealed that when S. aureus is metal-starved by the host, FdaB functionally replaces the metal-dependent isozyme FbaA, thereby allowing S. aureus to resist host-imposed metal starvation in culture. Although metal-dependent aldolases are canonically zinc-dependent, this work uncovered that FbaA requires manganese for activity and that FdaB protects S. aureus from manganese starvation. Both FbaA and FdaB contribute to the ability of S. aureus to cause invasive disease in wild-type mice. However, the virulence defect of a strain lacking FdaB was reversed in calprotectin-deficient mice, which have defects in manganese sequestration, indicating that this isozyme contributes to the ability of this pathogen to overcome manganese limitation during infection. Cumulatively, these observations suggest that the expression of the metal-independent aldolase FdaB allows S. aureus to alleviate the increased demand for manganese that glucose consumption imposes, and highlights the cofactor flexibility of even established metalloenzyme families. IMPORTANCE Staphylococcus aureus and other pathogens consume glucose during infection. Glucose utilization increases the demand for transition metals, such as manganese, a nutrient that the host limits as a defense mechanism against invading pathogens. Therefore, pathogenic bacteria must balance glucose and manganese requirements during infection. The two-component system ArlRS is an important regulator that allows S. aureus to adapt to both glucose and manganese starvation. Among the genes regulated by ArlRS is the metal-independent fructose 1,6-bisphosphate aldolase fdaB, which functionally substitutes for the metal-dependent isoenzyme FbaA and enables S. aureus to survive host-imposed manganese starvation. Unexpectedly, and differing from most characterized metal-dependent aldolases, FbaA requires manganese for activity. Cumulatively, these findings reveal a new mechanism for overcoming nutritional immunity as well as the cofactor plasticity of even well-characterized metalloenzyme families.


Subject(s)
Manganese , Staphylococcal Infections , Animals , Mice , Manganese/metabolism , Fructose-Bisphosphate Aldolase/genetics , Fructose-Bisphosphate Aldolase/metabolism , Staphylococcus aureus/metabolism , Isoenzymes/metabolism , Metals/metabolism , Bacteria/metabolism , Aldehyde-Lyases/metabolism , Staphylococcal Infections/microbiology
9.
mBio ; 13(3): e0098522, 2022 06 28.
Article in English | MEDLINE | ID: mdl-35658538

ABSTRACT

Group B Streptococcus (GBS) is associated with severe infections in utero and in newborn populations, including pneumonia, sepsis, and meningitis. GBS vaginal colonization of the pregnant mother is an important prerequisite for transmission to the newborn and the development of neonatal invasive disease; however, our understanding of the factors required for GBS persistence and ascension in the female reproductive tract (FRT) remains limited. Here, we utilized a GBS mariner transposon (Krmit) mutant library previously developed by our group and identified underrepresented mutations in 535 genes that contribute to survival within the vaginal lumen and colonization of vaginal, cervical, and uterine tissues. From these mutants, we identified 47 genes that were underrepresented in all samples collected, including mtsA, a component of the mtsABC locus, encoding a putative manganese (Mn2+)-dependent ATP-binding cassette transporter. RNA sequencing analysis of GBS recovered from the vaginal tract also revealed a robust increase of mtsA expression during vaginal colonization. We engineered an ΔmtsA mutant strain and found by using inductively coupled plasma mass spectrometry that it exhibited decreased concentrations of intracellular Mn2+, confirming its involvement in Mn2+ acquisition. The ΔmtsA mutant was significantly more susceptible to the metal chelator calprotectin and to oxidative stressors, including both H2O2 and paraquat, than wild-type (WT) GBS. We further observed that the ΔmtsA mutant strain exhibited a significant fitness defect in comparison to WT GBS in vivo by using a murine model of vaginal colonization. Taken together, these data suggest that Mn2+ homeostasis is an important process contributing to GBS survival in the FRT. IMPORTANCE Morbidity and mortality associated with GBS begin with colonization of the female reproductive tract (FRT). To date, our understanding of the factors required for GBS persistence in this environment remain limited. We identified several necessary systems for initial colonization of the vaginal lumen and penetration into the reproductive tissues via transposon mutagenesis sequencing. We determined that mutations in mtsA, the gene encoding a protein putatively involved in manganese (Mn2+) transport, were significantly underrepresented in all in vivo samples collected. We also show that mtsA contributes to Mn2+ acquisition and GBS survival during metal limitation by calprotectin, a metal-chelating protein complex. We further demonstrate that a mutant lacking mtsA is hypersusceptible to oxidative stress induced by both H2O2 and paraquat and has a severe fitness defect compared to WT GBS in the murine vaginal tract. This work reveals the importance of Mn2+ homeostasis at the host-pathogen interface in the FRT.


Subject(s)
Manganese , Streptococcal Infections , Animals , Female , Genomics , Homeostasis , Hydrogen Peroxide , Leukocyte L1 Antigen Complex , Mice , Paraquat , Pregnancy , Streptococcal Infections/genetics , Streptococcus agalactiae/genetics , Vagina
10.
J Am Med Dir Assoc ; 23(7): 1257-1261, 2022 07.
Article in English | MEDLINE | ID: mdl-35381191

ABSTRACT

BACKGROUND/OBJECTIVES: Direct care workers frequently encounter difficult interactions with the patients they serve and experience frustration and burnout. The current study tested a hypothesized model in which predictors of caregiver abuse risk (emotional dysregulation, difficulty managing patient behavior, and workplace satisfaction) were mediated by symptoms of burnout. DESIGN: The study used an online cross-sectional survey design. SETTING AND PARTICIPANTS: The study was implemented online via Qualtrics. Participants were 206 direct care workers (eg, certified nursing assistants, patient care technicians, home health aides, and medical assistants). MEASUREMENTS: All respondents completed the Caregiver Abuse Screen (CASE), Difficulty with Emotional Regulation Scale (DERS-SF), and the Abbreviated Maslach Burnout Inventory. Demographic data and employment history were also collected. Correlational methods, including path analysis, were used to assess associations between study variables. RESULTS: More than half of this heterogenous sample endorsed significant risk for engaging in patient abuse. Path analysis suggested emotional dysregulation and low workplace satisfaction were associated with greater risk of patient abuse, and these associations were partially and simultaneously mediated by burnout facets of depersonalization and emotional exhaustion. CONCLUSIONS AND IMPLICATIONS: This study provided preliminary support for a model of caregiver abuse in which underlying difficulties regulating emotions convey risk for caregiver abuse via burnout facets including emotional exhaustion and depersonalization. Enhancing basic emotion regulation skills and reducing burnout in direct care staff may reduce the risk of abuse for older adults. Thus, providing training necessary to help direct care workers manage their own emotions in order to better recognize, understand, and respond effectively to the needs of older adults may reduce staff burnout and, consequently, lower the risk of abuse for older adults.


Subject(s)
Burnout, Professional , Workplace , Aged , Burnout, Professional/psychology , Cross-Sectional Studies , Emotions , Humans , Job Satisfaction , Personal Satisfaction , Surveys and Questionnaires , Workplace/psychology
11.
Inhal Toxicol ; 34(3-4): 90-98, 2022.
Article in English | MEDLINE | ID: mdl-35275758

ABSTRACT

While some in vitro and in vivo experiments have studied the toxic effects of e-cigarette (e-cig) components, the typical aerosol properties released from e-cigarettes have not been well characterized. In the present study, we characterized the variability in mass concentration and particle size distribution associated with the aerosol generation of different devices and e-liquid compositions in an experimental setup. The findings of this study indicate a large inter-day variability in the experiments, likely due to poor quality control in some e-cig devices, pointing to the need for a better understanding of all the factors affecting exposures in in vitro and in vivo experiments, and the development of standardized protocols for generation and measurement of e-cig aerosols.


Subject(s)
Electronic Nicotine Delivery Systems , Aerosols
12.
Int J Lab Hematol ; 44(2): 414-423, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34786864

ABSTRACT

INTRODUCTION: Management of hemophilia A has changed significantly in the past few years with the expansion of new and/or modified products as treatment options. Unfortunately, many of the standard factor VIII assays do not always accurately measure all available treatment products; therefore, the laboratory must investigate various assay algorithms to ensure the reporting of the correct results. METHODS: Requirements for factor testing, diagnosis and severity levels, product testing, factor VIII inhibitor detection and titers, are evaluated, and potential algorithms are created for optimal assessment of patients with hemophilia A. RESULTS: The potential for inaccurate result reporting for patients with hemophilia A or those being treated with the myriad of products has left many laboratories uncertain as to which assay algorithm to implement to ensure reporting the correct results for all products used in their hemophilia program. Algorithms for using either One-stage Clotting assays or Chromogenic assays or a combination of both types of assays are presented for each laboratory to implement based on their clinical situation. CONCLUSIONS: Several algorithms are considered based on the needs of the clinical providers and their patients. Each laboratory must select a testing algorithm that is cost-effective and within available resources, yet that encompasses the needs of their providers and patients. Laboratory personnel must consider all assay uses (factor VIII levels, different products, interfering products, and inhibitor titers) in determining the best algorithm for their laboratory. This paper is a starting guide for developing the best factor VIII testing assays and protocols for your laboratory.


Subject(s)
Hemophilia A , Hemostatics , Blood Coagulation Tests/methods , Factor VIII/therapeutic use , Hemophilia A/diagnosis , Hemophilia A/drug therapy , Hemostatics/therapeutic use , Humans , Laboratories
13.
J Health Serv Psychol ; 47(3): 119-127, 2021.
Article in English | MEDLINE | ID: mdl-34423313

ABSTRACT

A third survey of the practice of licensed psychologists during the pandemic conducted in June 2021 revealed that the rapid adoption of telepsychological service provision has continued approximately 15 months after a national public health emergency was declared. Most respondents intend to make telepsychology a permanent component of their practice going forward. Other notable findings from our survey revealed that after an initial decline in caseload reported in the early days of the pandemic, the majority of psychologists surveyed now report an increase in caseload, often necessitating the establishment of a waitlist. Respondents reported that their patients/clients are more accepting of telepsychology than in our previous survey. That said, a significant minority of psychologists expressed concerns that this technology will negatively affect their future practice. Results also indicated that psychologists are encountering greater symptom acuity among their patients associated with the pandemic, including an increase in reports of suicidal thinking or behavior. Supplementary Information: The online version contains supplementary material available at 10.1007/s42843-021-00044-3.

14.
Eur Phys J A Hadron Nucl ; 57(4): 136, 2021.
Article in English | MEDLINE | ID: mdl-33897299

ABSTRACT

In recent years there has been much progress on the investigation of the QCD phase diagram with lattice QCD simulations. In this review we focus on the developments in the last two years. Especially the addition of external influences or new parameter ranges yields an increasing number of interesting results. We discuss the progress for small, finite densities from both extrapolation-based methods (Taylor expansion and analytic continuation for imaginary chemical potential) and complex Langevin simulations, for heavy quark bound states (quarkonium), the dependence on the quark masses (Columbia plot) and the influence of a magnetic field. Many of these conditions are relevant for the understanding of both the QCD transition in the early universe and heavy ion collision experiments, which are conducted for example at the LHC and RHIC.

15.
J Thromb Haemost ; 19(1): 68-74, 2021 01.
Article in English | MEDLINE | ID: mdl-33405382

ABSTRACT

Hereditary deficiencies of protein S (PS) increase the risk of venous thrombosis; however, assessing the plasma levels of PS can be difficult because of its complex physiological interactions in plasma, sample-related preanalytical variables, and numerous acquired disease processes. Reliable laboratory assays are essential for accurate evaluation of PS when diagnosing a congenital deficiency based on the plasma phenotype alone. This report presents the current evidence-based recommendations for clinical PS assays as well as when to test for PS abnormalities.


Subject(s)
Protein S Deficiency , Venous Thrombosis , Blood Coagulation , Clinical Laboratory Techniques , Communication , Humans , Protein S , Protein S Deficiency/diagnosis , Protein S Deficiency/genetics , Venous Thrombosis/diagnosis
16.
J Health Serv Psychol ; 46(4): 145-154, 2020.
Article in English | MEDLINE | ID: mdl-33225314

ABSTRACT

We conducted a survey of licensed psychologists at two weeks and again at six months after the declaration of a national emergency related to the COVID-19 pandemic. This article describes the results of the second survey conducted approximately six months after the crisis began. The rapid shift to telepsychological services seen in the first survey in the pandemic has solidified in the second survey. More providers reported delivering a larger percentage of services via telepsychology than early in the pandemic. The majority of respondents do not anticipate resuming in-person services until after a vaccine is made available, although a consistent minority reports ongoing in-person service provision. A majority reported their patients had appropriate access to internet and telepsychological service platforms, although one-fifth of respondents reported their patients had difficulty accessing such services. Early concerns about technological or regulatory problems involved in telepsychology are no longer evident. Most respondents indicated they will continue to use telepsychological services for the delivery of some of their psychological services after the pandemic ends. Forty-five percent knew of individuals who contracted the disease, 13% knew someone who died of the disease, and 2% reported contracted the disease themselves.

17.
mBio ; 11(6)2020 11 10.
Article in English | MEDLINE | ID: mdl-33173000

ABSTRACT

Nutritional immunity is an elegant host mechanism used to starve invading pathogens of necessary nutrient metals. Calprotectin, a metal-binding protein, is produced abundantly by neutrophils and is found in high concentrations within inflammatory sites during infection. Group B Streptococcus (GBS) colonizes the gastrointestinal and female reproductive tracts and is commonly associated with severe invasive infections in newborns such as pneumonia, sepsis, and meningitis. Although GBS infections induce robust neutrophil recruitment and inflammation, the dynamics of GBS and calprotectin interactions remain unknown. Here, we demonstrate that disease and colonizing isolate strains exhibit susceptibility to metal starvation by calprotectin. We constructed a mariner transposon (Krmit) mutant library in GBS and identified 258 genes that contribute to surviving calprotectin stress. Nearly 20% of all underrepresented mutants following treatment with calprotectin are predicted metal transporters, including known zinc systems. As calprotectin binds zinc with picomolar affinity, we investigated the contribution of GBS zinc uptake to overcoming calprotectin-imposed starvation. Quantitative reverse transcriptase PCR (qRT-PCR) revealed a significant upregulation of genes encoding zinc-binding proteins, adcA, adcAII, and lmb, following calprotectin exposure, while growth in calprotectin revealed a significant defect for a global zinc acquisition mutant (ΔadcAΔadcAIIΔlmb) compared to growth of the GBS wild-type (WT) strain. Furthermore, mice challenged with the ΔadcAΔadcAIIΔlmb mutant exhibited decreased mortality and significantly reduced bacterial burden in the brain compared to mice infected with WT GBS; this difference was abrogated in calprotectin knockout mice. Collectively, these data suggest that GBS zinc transport machinery is important for combatting zinc chelation by calprotectin and establishing invasive disease.IMPORTANCE Group B Streptococcus (GBS) asymptomatically colonizes the female reproductive tract but is a common causative agent of meningitis. GBS meningitis is characterized by extensive infiltration of neutrophils carrying high concentrations of calprotectin, a metal chelator. To persist within inflammatory sites and cause invasive disease, GBS must circumvent host starvation attempts. Here, we identified global requirements for GBS survival during calprotectin challenge, including known and putative systems involved in metal ion transport. We characterized the role of zinc import in tolerating calprotectin stress in vitro and in a mouse model of infection. We observed that a global zinc uptake mutant was less virulent than the parental GBS strain and found calprotectin knockout mice to be equally susceptible to infection by wild-type (WT) and mutant strains. These findings suggest that calprotectin production at the site of infection results in a zinc-limited environment and reveals the importance of GBS metal homeostasis to invasive disease.


Subject(s)
Leukocyte L1 Antigen Complex/metabolism , Streptococcal Infections/metabolism , Streptococcus agalactiae/metabolism , Zinc/metabolism , Animals , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Female , Humans , Leukocyte L1 Antigen Complex/genetics , Meningitis, Bacterial/genetics , Meningitis, Bacterial/metabolism , Meningitis, Bacterial/microbiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neutrophils/metabolism , Streptococcal Infections/genetics , Streptococcal Infections/microbiology , Streptococcus agalactiae/genetics , Streptococcus agalactiae/growth & development , Streptococcus agalactiae/pathogenicity , Virulence
18.
J Bacteriol ; 202(22)2020 10 22.
Article in English | MEDLINE | ID: mdl-32868400

ABSTRACT

Phosphate is an essential nutrient that Staphylococcus aureus and other pathogens must acquire from the host during infection. While inorganic monophosphate (Pi) is the preferred source of this nutrient, bacteria can also obtain it from phosphate-containing organic molecules. The Pi-responsive regulator PhoPR is necessary for S. aureus to cause infection, suggesting that Pi is not freely available during infection and that this nutrient must be obtained from other sources. However, the organophosphates from which S. aureus can obtain phosphate are unknown. We evaluated the ability of 58 phosphorus-containing molecules to serve as phosphate sources for S. aureus Forty-six of these compounds, including phosphorylated amino acids, sugars, and nucleotides, supported growth. Among the organophosphate sources was glycerol-3-phosphate (G3P), which is commonly found in the mammalian host. Differing from the model organism Escherichia coli, S. aureus does not import G3P intact to obtain Pi Instead, S. aureus relies on the phosphatase PhoB to release Pi from G3P, which is subsequently imported by Pi transporters. To determine if this strategy is used by S. aureus to extract phosphate from other phosphate sources, we assessed the ability of PhoB- and Pi transporter-deficient strains to grow on the same library of phosphorus-containing molecules. Sixty percent of the substrates (28/46) relied on the PhoB/Pi transporter pathway, and an additional 10/46 (22%) were PhoB independent but still required Pi transport through the Pi transporters. Cumulatively, these results suggest that in Pi-limited environments, S. aureus preferentially generates Pi from organophosphates and then relies on Pi transporters to import this nutrient.IMPORTANCE For bacteria, the preferred form of the essential nutrient phosphate is inorganic monophosphate (Pi), but phosphate can also be extracted from a variety of phosphocompounds. Pathogens, including Staphylococcus aureus, experience Pi limitation within the host, suggesting that the use of alternative phosphate sources is important during infection. However, the alternative phosphate sources that can be used by S. aureus and others remain largely unexplored. We screened a library of phosphorus-containing compounds for the ability to support growth as a phosphate source. S. aureus could use a variety of phosphocompounds, including nucleotides, phosphosugars, and phosphoamino acids. Subsequent genetic analysis determined that a majority of these alternative phosphate sources are first processed extracellularly to liberate Pi, which is then imported through Pi transporters.


Subject(s)
Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial , Organophosphates/metabolism , Phosphates/metabolism , Staphylococcus aureus/metabolism , Bacterial Proteins/genetics , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Nutrients , Staphylococcus aureus/genetics , Staphylococcus aureus/growth & development
19.
Phys Rev Lett ; 125(5): 052001, 2020 Jul 31.
Article in English | MEDLINE | ID: mdl-32794881

ABSTRACT

We provide the most accurate results for the QCD transition line so far. We optimize the definition of the crossover temperature T_{c}, allowing for its very precise determination, and extrapolate from imaginary chemical potential up to real µ_{B}≈300 MeV. The definition of T_{c} adopted in this work is based on the observation that the chiral susceptibility as a function of the condensate is an almost universal curve at zero and imaginary µ_{B}. We obtain the parameters κ_{2}=0.0153(18) and κ_{4}=0.00032(67) as a continuum extrapolation based on N_{t}=10, 12, 16 lattices with physical quark masses. We also extrapolate the peak value of the chiral susceptibility and the width of the chiral transition along the crossover line. In fact, both of these are consistent with a constant function of µ_{B}. We see no sign of criticality in the explored range.

20.
J Health Serv Psychol ; 46(2): 51-57, 2020.
Article in English | MEDLINE | ID: mdl-32395720

ABSTRACT

Psychological practice has changed dramatically over the past 125 years. The two world wars both served to stimulate and change the scope of practice for psychologists. We surveyed over 3,000 doctoral psychologists about the impact of the COVID-19 health crisis on their clinical practices. Practice changed from primarily in-office to mostly telepsychology practice over the course of 2 weeks in March of 2020. The long-term effect on professional practice in psychology is not known.

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