Author
Jonathan E. Schmitz
Other affiliations: University of Cambridge, Vanderbilt University, Rockefeller University ...read more
Bio: Jonathan E. Schmitz is an academic researcher from Vanderbilt University Medical Center. The author has contributed to research in topics: Medicine & Lysin. The author has an hindex of 17, co-authored 53 publications receiving 1536 citations. Previous affiliations of Jonathan E. Schmitz include University of Cambridge & Vanderbilt University.
Papers published on a yearly basis
Papers
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TL;DR: In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19, and real-time reverse transcription-PCR assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools.
Abstract: The COVID-19 outbreak has had a major impact on clinical microbiology laboratories in the past several months. This commentary covers current issues and challenges for the laboratory diagnosis of infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19. Appropriate measures are required to keep laboratory staff safe while producing reliable test results. In the analytic stage, real-time reverse transcription-PCR (RT-PCR) assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools. In the postanalytical stage, testing results should be carefully interpreted using both molecular and serological findings. Finally, random-access, integrated devices available at the point of care with scalable capacities will facilitate the rapid and accurate diagnosis and monitoring of SARS-CoV-2 infections and greatly assist in the control of this outbreak.
955 citations
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TL;DR: A novel bacteriophage lysin (PlySs2), derived from a Streptococcus suis phage, with broad lytic activity against MRSA, vancomycin-intermediate S. aureus, and other Gram-positive pathogens is identified.
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A streptococcus [GrAS]) cause serious and sometimes fatal human diseases. They are among the many Gram-positive pathogens for which resistance to leading antibiotics has emerged. As a result, alternative therapies need to be developed to combat these pathogens. We have identified a novel bacteriophage lysin (PlySs2), derived from a Streptococcus suis phage, with broad lytic activity against MRSA, vancomycin-intermediate S. aureus (VISA), Streptococcus suis, Listeria, Staphylococcus simulans, Staphylococcus epidermidis, Streptococcus equi, Streptococcus agalactiae (group B streptococcus [GBS]), S. pyogenes, Streptococcus sanguinis, group G streptococci (GGS), group E streptococci (GES), and Streptococcus pneumoniae. PlySs2 has an N-terminal cysteine-histidine aminopeptidase (CHAP) catalytic domain and a C-terminal SH3b binding domain. It is stable at 50°C for 30 min, 37°C for >24 h, 4°C for 15 days, and −80°C for >7 months; it maintained full activity after 10 freeze-thaw cycles. PlySs2 at 128 μg/ml in vitro reduced MRSA and S. pyogenes growth by 5 logs and 3 logs within 1 h, respectively, and exhibited a MIC of 16 μg/ml for MRSA. A single, 2-mg dose of PlySs2 protected 92% (22/24) of the mice in a bacteremia model of mixed MRSA and S. pyogenes infection. Serially increasing exposure of MRSA and S. pyogenes to PlySs2 or mupirocin resulted in no observed resistance to PlySs2 and resistance to mupirocin. To date, no other lysin has shown such notable broad lytic activity, stability, and efficacy against multiple, leading, human bacterial pathogens; as such, PlySs2 has all the characteristics to be an effective therapeutic.
175 citations
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TL;DR: A case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease is described.
Abstract: Persistent neutrophilic meningitis presents a diagnostic challenge, because the differential diagnosis is broad and includes atypical infectious causes. We describe a case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease. An epidural glucocorticoid injection was identified as a potential route of entry for this organism into the central nervous system, and the case was reported to the state health department.
86 citations
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Central European Institute of Technology1, Rockefeller University2, Masaryk University3, Vanderbilt University4, Montana State University5, Stanford University6, Cedars-Sinai Medical Center7, University of California, Irvine8, University of California, San Francisco9, Scripps Health10, University of California, San Diego11, Kaiser Permanente12, Brown University13, Kaiser Permanente Oakland Medical Center14, Celgene15, University of California, Los Angeles16, Johns Hopkins University17, University of Southern California18, Ludwig Maximilian University of Munich19
TL;DR: This study confirms that Propionibacterium acnes is prevalent in herniated disc tissue, and provides the first visual evidence of P. acnes biofilm in the intervertebral discs.
Abstract: Background In previous studies, Propionibacterium acnes was
cultured from intervertebral disc tissue of similar to 25% of
patients undergoing microdiscectomy, suggesting a possible link
between chronic bacterial infection and disc degeneration.
However, given the prominence of P. acnes as a skin commensal,
such analyses often struggled to exclude the alternate
possibility that these organisms represent perioperative
microbiologic contamination. This investigation seeks to
validate P. acnes prevalence in resected disc cultures, while
providing microscopic evidence of P. acnes biofilm in the
intervertebral discs. Methods Specimens from 368 patients
undergoing microdiscectomy for disc herniation were divided
into several fragments, one being homogenized, subjected to
quantitative anaerobic culture, and assessed for bacterial
growth, and a second fragment frozen for additional analyses.
Colonies were identified by MALDI-TOF mass spectrometry and P.
acnes phylotyping was conducted by multiplex PCR. For a sub-set
of specimens, bacteria localization within the disc was
assessed by microscopy using confocal laser scanning and FISH.
Results Bacteria were cultured from 162 discs (44%), including
119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was
cultured exclusively; in 30 cases, it was isolated in
combination with other bacteria (primarily coagulase-negative
Staphylococcus spp.) Among positive specimens, the median P.
acnes bacterial burden was 350 CFU/g (12 - similar to 20,000
CFU/g). Thirtyeight P. acnes isolates were subjected to
molecular sub-typing, identifying 4 of 6 defined phylogroups:
IA1, IB, IC, and II. Eight culture-positive specimens were
evaluated by fluorescence microscopy and revealed P. acnes in
situ. Notably, these bacteria demonstrated a biofilm
distribution within the disc matrix. P. acnes bacteria were
more prevalent in males than females (39% vs. 23%, p = 0.0013).
Conclusions This study confirms that P. acnes is prevalent in
herniated disc tissue. Moreover, it provides the first visual
evidence of P. acnes biofilms within such specimens, consistent
with infection rather than microbiologic contamination.
75 citations
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TL;DR: This study confirms that MRS‐detectable lipids accumulate in tumor cells undergoing apoptosis, and therefore may be usable as a marker for the noninvasive detection of tumor cell apoptosis in the clinic.
Abstract: Proton MRS detection of cellular lipid accumulation has been suggested as a noninvasive method for detecting apoptosis or programmed cell death (PCD) in vivo. The spectral changes that have been observed in apoptotic cells include a general increase in lipid signals and a specific increase in the ratio of the lipid methylene-to-methyl peak intensities. These changes were investigated here following drug-induced apoptosis, both in vitro with a murine lymphoma cell line (EL-4) and in vivo following implantation of these cells to form subcutaneous tumors. Fluorescence microscopy and flow cytometric measurements with a lipophilic dye revealed an accumulation of cytoplasmic lipid droplets in isolated EL-4 cells undergoing etoposide-induced apoptosis. 1H MR spectra (both diffusion-weighted (DW) and unweighted) showed an increase in lipid signals. However, the methylene/methyl peak ratio showed only minimal changes. Localized in vivo spectroscopy of EL-4 tumors also showed an increase in lipid signals, including a signal from polyunsaturated lipid at 2.8 ppm, after 16–24 h of drug treatment. Again there was no significant change in the methylene/methyl peak ratio. This study confirms that MRS-detectable lipids accumulate in tumor cells undergoing apoptosis, and therefore may be usable as a marker for the noninvasive detection of tumor cell apoptosis in the clinic. Magn Reson Med 54:43–50, 2005. © 2005 Wiley-Liss, Inc.
62 citations
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TL;DR: It is suggested that SARS-CoV2-specific IgG or IgM seroconversion occurs within 20 days post symptom onset and may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections.
Abstract: We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
2,473 citations
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TL;DR: A blocking assay based on the recombinant receptor-binding domain of SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 receptor provides an alternative to conventional antibody neutralization assays requiring live virus.
Abstract: A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.
947 citations
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TL;DR: In lymphoma-bearing mice injected intravenously with hyperpolarized [1-13C]pyruvate, it is shown that the lactate dehydrogenase–catalyzed flux of 13C label between the carboxyl groups of pyruvates and lactate in the tumor can be measured using 13C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy.
Abstract: Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-(13)C]pyruvate that the lactate dehydrogenase-catalyzed flux of (13)C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using (13)C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors. The technique could provide a new way to assess tumor responses to treatment in the clinic.
840 citations
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TL;DR: The major principles underlying effects of dietary constituents on the gut microbiota are reviewed, resolving aspects of the diet–microbiota–host crosstalk, and the promises and challenges of incorporating microbiome data into dietary planning are presented.
Abstract: Since the renaissance of microbiome research in the past decade, much insight has accumulated in comprehending forces shaping the architecture and functionality of resident microorganisms in the human gut. Of the multiple host-endogenous and host-exogenous factors involved, diet emerges as a pivotal determinant of gut microbiota community structure and function. By introducing dietary signals into the nexus between the host and its microbiota, nutrition sustains homeostasis or contributes to disease susceptibility. Herein, we summarize major concepts related to the effect of dietary constituents on the gut microbiota, highlighting chief principles in the diet-microbiota crosstalk. We then discuss the health benefits and detrimental consequences that the interactions between dietary and microbial factors elicit in the host. Finally, we present the promises and challenges that arise when seeking to incorporate microbiome data in dietary planning and portray the anticipated revolution that the field of nutrition is facing upon adopting these novel concepts.
806 citations