Jan-Peter van Pijkeren

Jan-Peter van Pijkeren
University of Wisconsin–Madison | UW · Department of Food Science

PhD

About

78
Publications
9,526
Reads
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2,594
Citations
Citations since 2016
16 Research Items
1880 Citations
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
Additional affiliations
September 2008 - May 2013
Michigan State University
Position
  • PostDoc Position

Publications

Publications (78)
Article
Full-text available
Innovative new genome engineering technologies for manipulating chromosomes have appeared in the last decade. One of these technologies, recombination mediated genetic engineering (recombineering) allows for precision DNA engineering of chromosomes and plasmids in Escherichia coli. Single-stranded DNA recombineering (SSDR) allows for the generation...
Article
Full-text available
Clustered regularly interspaced palindromic repeats (CRISPRs) and the CRISPR-associated (Cas) nuclease protect bacteria and archeae from foreign DNA by site-specific cleavage of incoming DNA. Type-II CRISPR–Cas systems, such as the Streptococcus pyogenes CRISPR–Cas9 system, can be adapted such that Cas9 can be guided to a user-defined site in the c...
Article
Full-text available
The ability to efficiently generate targeted point mutations in the chromosome without the need for antibiotics, or other means of selection, is a powerful strategy for genome engineering. Although oligonucleotide-mediated recombineering (ssDNA recombineering) has been utilized in Escherichia coli for over a decade, the successful adaptation of ssD...
Article
Bacteria-mediated transfer of plasmid DNA to mammalian cells (bactofection) has been shown to have significant potential as an approach to express heterologous proteins in various cell types. This is achieved through entry of the entire bacterium into cells, followed by release of plasmid DNA. In a murine model, we show that Listeria monocytogenes...
Article
Full-text available
Lactobacillus reuteri R2lc and 2010 are pigmented rat intestinal isolates. L. reuteri R2lc has been studied in different animal disease models, including colitis and acute liver injury. We sequenced both isolates and identified novel secondary metabolite gene clusters, which may be linked to the probiotic potential of these strains.
Article
The mammalian intestinal tract contains a complex microbial ecosystem with many lysogens, which are bacteria containing dormant phages (prophages) inserted within their genomes. Approximately half of intestinal viruses are derived from lysogens, suggesting that these bacteria encounter triggers that promote phage production. We show that prophages...
Article
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Lactobacillus reuteri has the potential to be developed as a microbial therapeutic delivery platform because of an established safety profile, health-promoting properties, and available genome editing tools. Here, we showed that L. reuteri VPL1014 exhibits a low mutation rate compared to other gram-positive bacteria, which we expect will contribute...
Article
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Background: Lactic acid bacteria (LAB) are one of the microorganisms of choice for the development of protein delivery systems for therapeutic purposes. Although there are numerous tools to facilitate genome engineering of lactobacilli; transformation efficiency still limits the ability to engineer their genomes. While genetically manipulating Lac...
Article
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Objective Antimicrobial C-type lectin regenerating islet-derived 3 gamma (REG3G) is suppressed in the small intestine during chronic ethanol feeding. Our aim was to determine the mechanism that underlies REG3G suppression during experimental alcoholic liver disease. Design Interleukin 22 (IL-22) regulates expression of REG3G. Therefore, we investi...
Article
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A mechanistic understanding of microbe-host interactions is critical to developing therapeutic strategies for targeted modulation of the host immune system. Different members of the gut symbiont species Lactobacillus reuteri modulate host health by, for example, reduction of intestinal inflammation. Previously, it was shown that L. reuteri activate...
Article
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The peptidoglycan composition in lactic acid bacteria dictates vancomycin resistance. Vancomycin binds relatively poorly to peptidoglycan ending in D-alanyl-Dlactate and binds with high affinity to peptidoglycan ending in D-alanyl-D-alanine (D-Ala- D-Ala), which results in vancomycin resistance and sensitivity, respectively. The enzyme responsible...
Article
Comprehension of underlying mechanisms of probiotic action will support rationale selection of probiotic strains and targeted clinical study design with a higher likelihood of success. This will consequently contribute to better substantiation of health claims. Here, we aim to provide a perspective from a microbiology point of view that such compre...
Article
Genome Editing of Food-Grade Lactobacilli To Develop Therapeutic Probiotics, Page 1 of 2 Abstract Lactic acid bacteria have been used historically for food manufacturing mainly to ensure preservation via fermentation. More recently, lactic acid bacteria have been exploited to promote human health, and many strains serve as industrial workhorses....
Article
Full-text available
Background & aims: Alcoholic liver disease is a leading cause of mortality. Chronic alcohol consumption is accompanied by intestinal dysbiosis, and development of alcoholic liver disease requires gut-derived bacterial products. However, little is known about how alterations to the microbiome contribute to pathogenesis of alcoholic liver disease....
Article
Certain bacteria have emerged as biological gene vectors with natural tumor specificity, capable of specifically delivering genes or gene products to the tumor environment when intravenously (i.v.) administered to rodent models. Here, we describe procedures for studying this phenomenon in vitro and in vivo for both invasive and noninvasive bacteria...
Article
Full-text available
Lactobacillus reuteri, a symbiotic inhabitant of the gastrointestinal tract in humans and animals, is marketed as a probiotic. The ability to adhere to intestinal epithelial cells and mucus are interesting properties with regards to probiotic features such as colonization of the gastrointestinal tract, competitive exclusion of pathogens and interac...
Article
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Lactococcal phages Tuc2009 and TP901-1 possess a conserved tail fibre, called a Tail-Associated Lysin (referred to as Tal2009 for Tuc2009, and Tal901-1 for TP901-1), suspended from their tail tips that projects a Peptidoglycan-Hydrolase (PGH) domain towards a potential host bacterium. Tal2009 and Tal901-1 can undergo proteolytic processing mid-prot...
Article
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In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Tempor...
Article
Full-text available
Single-stranded DNA (ssDNA) recombineering is a technology which is used to make subtle changes in the chromosome of several bacterial genera. Cells which express a single-stranded DNA binding protein (RecT or Bet) are transformed with an oligonucleotide which is incorporated via an annealing and replication-dependent mechanism. By in silico analys...
Article
The marketplace for probiotic foods is burgeoning, measured in billions of euro per annum. It is imperative, however, that all bacterial strains are fully assessed for human safety. The ability to bind fibrinogen is considered a potential pathogenicity trait that can lead to platelet aggregation, serious medical complications, and in some instances...
Article
Full-text available
The probiotic effects of Lactobacillus reuteri have been speculated to partly depend on its capacity to produce the antimicrobial substance reuterin during the reduction of glycerol in the gut. In this study, the potential of this process to protect human intestinal epithelial cells against infection with Salmonella enterica serovar Typhimurium was...
Article
Full-text available
Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced b...
Data
Triple quadrupole mass spectrometry standard curve. Standard curve generated from deuterated histamine and used for the triple quadrupole MS quantification of histamine in HILIC-HPLC fractions and bacterial culture supernatant. Each sample was spiked with deuterated histamine as an internal standard. (TIF)
Data
THP-1 cells express the H1 and H2 receptors. Unstimulated THP-1 cells were examined for cell surface expression of the histamine H1 and H2 receptors. Cells were labeled with rabbit anti-human H1R or H2R pAb and FITC-conjugated goat anti-rabbit IgG pAb or FITC-conjugated goat anti-rabbit IgG pAb alone (IgG Control) and analyzed with FACS. Shown is o...
Data
Elevated cAMP inhibited TNF production from activated human monocytoid cells. Treatment of TLR2-stimulated THP-1 cells with a synthetic analog of cAMP, dcAMP, was sufficient to inhibit TNF production. Results represent the mean ± SD (n = 3), *p value<0.05 compared to medium control. (TIF)
Data
TNF-inhibitory phenotype was modified by the carbon source in the growth medium. Supplementing the growth medium with various simple sugars, such as glucose, glucose+fructose, and sucrose, altered the ability of TFA-treated cell pellets (CP) from L. reuteri 6475 to inhibit TNF production. Results represent the mean ± SD (n = 3), *p value<0.05 compa...
Data
A complete histidine decarboxylase gene cluster was found only in lactobacilli. Analysis of the HMP reference genomes (GI bacteria) for histidine decarboxylase gene homologs revealed that out of 349 reference genomes, only four bacterial strains contained the complete histidine decarboxylase gene cluster. The strains were L. reuteri JCM 112, L. reu...
Data
Genes in the histidine decarboxylase gene cluster were necessary for production of histamine. A. Quantitative real-time PCR demonstrated increased expression of all three hdc genes, hdcA, hdcB, and hdcP, when L. reuteri 6475 was grown in LDMIIIG medium supplemented with 4 mg/mL L-histidine compared to unsupplemented LDMIIIG. Gene expression data we...
Data
Inhibition of ERK1/2 activation suppressed TNF production from activated human monocytoid cells. Inhibition of the MEK/ERK signaling pathway with a MEK-specific inhibitor, U0126, was sufficient to block TNF production. Results represent the mean ± SD (n = 3), *p value<0.05 compared to RPMI medium control, #p value<0.05 compared to LDMIIIG medium co...
Data
TNF-inhibitory compounds were isolated in three distinct HILIC-HPLC fractions. Compounds from TFA-treated L. reuteri cell pellets were separated based on relative hydrophobicity. A. TNF-inhibitory compounds from L. reuteri 6475 grown in a glucose-containing medium were isolated in 3 fractions (B3, B5, and B6). Results represent the mean ± SD (n = 3...
Data
Pixel density analysis of MEK1/2 and ERK1/2 immunoblots. Immunoblots of MEK1/2 and ERK1/2 were quantified by pixel density analysis. A. MEK1/2. Results represent the mean ± SEM (n = 3), *p value<0.05 compared to medium control. B. ERK1/2. Results represent the mean ± SEM (n = 3), *p value<0.05 compared to medium control, #p value<0.05 compared to L...
Article
Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression. We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse mod...
Article
Full-text available
Listeria monocytogenes is an intracellular pathogen that lyses the phagosomal vacuole of infected cells, proliferates in the host cell cytoplasm and can actively enter adjacent cells. The pathogen is therefore well suited to exploitation as a vector for the delivery of DNA to target cells as the lifecycle favors cellular targeting with vector ampli...
Article
Full-text available
Human infection by the gastric pathogen Helicobacter pylori is characterized by a robust immune response which rarely prevents persistent H. pylori colonization. Emerging evidence suggests that lactobacilli may reduce H. pylori infection rates and associated inflammation. In this study, we measured the ability of two model strains of Lactobacillus...
Article
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The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with...
Article
Full-text available
The genome of Lactobacillus salivarius UCC118 comprises a 1.83-Mb chromosome, a 242-kb megaplasmid (pMP118), and two smaller plasmids of 20 kb (pSF118-20) and 44 kb (pSF118-44). Annotation and bioinformatic analyses suggest that both of the smaller plasmids replicate by a theta replication mechanism. Furthermore, it appears that they are transmissi...
Article
Full-text available
The genome of Lactobacillus salivarius UCC118 includes a 242-kb megaplasmid, pMP118. We now show that 33 strains of L. salivarius isolated from humans and animals all harbor a megaplasmid, which hybridized with the repA and repE replication origin probes of pMP118. Linear megaplasmids that did not hybridize with the pMP118 repA probe were also foun...