Johanna L. M. Tjeerdsma-van Bokhoven

Utrecht University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Henk P. Haagsman

Utrecht University

Edwin J.A. Veldhuizen

Utrecht University

Albert van Dijk

Utrecht University

Viktoria A. F. Schneider

Utrecht University

Floris J. Bikker

Academic Center for Dentistry Amsterdam

Maaike R. Scheenstra

Leiden University Medical Center

Maarten Coorens

Karolinska University Hospital

George Posthuma

Utrecht University

A.J.M. Jansman

Wageningen University & Research

Monique H.G. Tersteeg‐Zijderveld

Utrecht University

Cooperative Institutions

Utrecht University

University Medical Center Utrecht

Wageningen University & Research

University Medical Center

Heidelberg University

University of Amsterdam

University Hospital Heidelberg

University of Groningen

Academic Medical Center

Vrije Universiteit Amsterdam

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Imaging the Antistaphylococcal Activity of CATH-2: Mechanism of Attack and Regulation of Inflammatory Response

mSphere (2017)

Viktoria A. F. Schneider Maarten Coorens Johanna L. M. Tjeerdsma-van Bokhoven George Posthuma Albert van Dijk

Due to the high use of antibiotics in both human and veterinary settings, many bacteria have become resistant to those antibiotics that we so heavily rely on. Methicillin-resistant S. aureus (MRSA) is one of these difficult-to-treat resistant pathogens for which novel antimicrobial therapies will be required in the near future. One novel approach could be the utilization of naturally occurring antimicrobial peptides, such as chicken CATH-2, which have been show to act against a wide variety of bacteria. However, before these peptides can be used clinically, more knowledge of their functions and mechanisms of action is required. In this study, we used live imaging and electron microscopy to visualize in detail how CATH-2 kills S. aureus , and we investigated how CATH-2 affects immune activation by S. aureus . Together, these results give a better understanding of how CATH-2 kills S. aureus and what the potential immunological consequences of this killing can be.

Cathelicidin

10.1128/msphere.00370-17

Cite

Citations (33)

Sub-lethal levels of carvacrol reduce Salmonella Typhimurium motility and invasion of porcine epithelial cells

Veterinary Microbiology (2011)

Jeanine Inamuco Andreas K. J. Veenendaal Sara A. Burt Jan A. Post Johanna L. M. Tjeerdsma-van Bokhoven

Carvacrol

10.1016/j.vetmic.2011.12.021

Cite

Citations (53)

Chicken heterophils are recruited to the site of Salmonella infection and release antibacterial mature Cathelicidin-2 upon stimulation with LPS

Molecular Immunology (2009)

Albert van Dijk Monique H.G. Tersteeg‐Zijderveld Johanna L. M. Tjeerdsma-van Bokhoven A.J.M. Jansman Edwin J.A. Veldhuizen

Cathelicidin

10.1016/j.molimm.2008.12.015

Cite

Citations (84)

d-enantiomers of CATH-2 enhance the response of macrophages against Streptococcus suis serotype 2

Journal of Advanced Research (2021)

Roel M. van Harten Johanna L. M. Tjeerdsma-van Bokhoven Astrid de Greeff Melanie D. Balhuizen Albert van Dijk

Due to the increase of antibiotic resistant bacterial strains, there is an urgent need for development of alternatives to antibiotics. Cathelicidins can be such an alternative to antibiotics having both a direct antimicrobial capacity as well as an immunomodulatory function. Previously, the full d-enantiomer of chicken cathelicidin-2 (d-CATH-2) has shown to prophylactically protect chickens against infection 7 days post hatch when administered in ovo three days before hatch.To further evaluate d-CATH-2 in mammals as a candidate for an alternative to antibiotics.In this study, the prophylactic capacity of d-CATH-2 and two truncated derivatives, d-C(1-21) and d-C(4-21), was determined in mammalian cells.Antibacterial assays; immune cell differentiation and modulation; cytotoxicity, isothermal titration calorimetry; in vivo prophylactic capacity of peptides in an S. suis infection model.d-CATH-2 and its derivatives were shown to have a strong direct antibacterial capacity against four different S. suis serotype 2 strains (P1/7, S735, D282, and OV625) in bacterial medium and even stronger in cell culture medium. In addition, d-CATH-2 and its derivatives ameliorated the efficiency of mouse bone marrow-derived macrophages (BMDM) and skewed mouse bone marrow-derived dendritic cells (BMDC) towards cells with a more macrophage-like phenotype. The peptides directly bind lipoteichoic acid (LTA) and inhibit LTA-induced activation of macrophages. In addition, S. suis killed by the peptide was unable to further activate mouse macrophages, which indicates that S. suis was eliminated by the previously reported silent killing mechanism. Administration of d-C(1-21) at 24 h or 7 days before infection resulted in a small prophylactic protection with reduced disease severity and reduced mortality of the treated mice.d-enantiomers of CATH-2 show promise as anti-infectives against pathogenic S. suis for application in mammals.

Cathelicidin

Streptococcus suis

10.1016/j.jare.2021.05.009

Cite

Citations (9)

Growth inhibition of heat-injured Enterococcus faecium by oligophosphates in a cured meat model

International Journal of Food Microbiology (2004)

J.H. Houben Johanna L. M. Tjeerdsma-van Bokhoven

Enterococcus faecium

10.1016/j.ijfoodmicro.2004.04.024

Cite

Citations (6)

Cathelicidins PMAP-36, LL-37 and CATH-2 are similar peptides with different modes of action

Scientific Reports (2019)

Maaike R. Scheenstra M. Belt Johanna L. M. Tjeerdsma-van Bokhoven Viktoria A. F. Schneider Soledad R. Ordoñez

Abstract Host defense peptides (HDPs) play a pivotal role in innate immunity and have, in addition to antimicrobial activity, also important immunomodulatory functions. Bacteria are less likely to develop resistance against HDPs because these peptides target and kill bacteria in multiple ways, as well as modulate the immune system. Therefore, HDPs, and derivatives thereof, are promising alternatives to traditional antibiotics. Hardly anything is known about the immunomodulatory functions of porcine cathelicidin PMAP-36. In this study, we aimed to determine both antibacterial and immunomodulatory activities of PMAP-36 comparing the properties of PMAP-36 analogs with two well-studied peptides, human LL-37 and chicken CATH-2. Transmission electron microscopy revealed different killing mechanisms of E . coli for PMAP-36, CATH-2 and LL-37. LL-37 binds LPS very weakly in contrast to PMAP-36, but it inhibits LPS activation of macrophages the strongest. The first 11 amino acids of the N-terminal side of PMAP-36 are dispensable for E . coli killing, LPS-neutralization and binding. Deletion of four additional amino acids resulted in a strong decrease in activity. The activity of full length PMAP-36 was not affected by monomerization, whereas the shorter analogs require dimerization for proper immunomodulatory activity but not for their antibacterial activity.

Cathelicidin

Antibacterial peptide

10.1038/s41598-019-41246-6

Cite

Citations (87)

Antimicrobial and Immunomodulatory Activity of PMAP-23 Derived Peptides

Protein and Peptide Letters (2017)

Edwin J.A. Veldhuizen Maaike R. Scheenstra Johanna L. M. Tjeerdsma-van Bokhoven Maarten Coorens Viktoria A. F. Schneider

The Porcine Myeloid Antibacterial Peptide (PMAP)-23 is a porcine host defence peptide with strong antibacterial activity against Gram-positive and Gram-negative bacteria, and fungi.PMAP-23 and truncated/mutated derivatives were tested for antibacterial and immunomodulatory activities to determine core elements of the peptide required for functionality.PMAP-23 and truncated and/or mutated derivatives were synthesized. Antibacterial activity against Gram positive and negative bacteria was determined using colony counting assays. Cytotoxicity was measured against red blood cells and epithelial cells. Peptide induced cytokine production of epithelial cells was determined by ELISA. LPS neutralization was measured using isothermal titration calorimetry and inhibition of LPS induced cytokine production by macrophages. The effect of peptides on phagocytosis was performed by measuring uptake of fluorescently labelled beads by porcine macrophages.Truncation of the peptide did not lead to a strong reduction in antibacterial activity, but interestingly, all C-terminal truncated forms were strongly inhibited by salt addition, unlike the full length peptide or the two N-terminally truncated peptides. None of the peptides were hemolytic or toxic in concentrations up to 40 μM. Full length PMAP-23 induced IL-8 production in porcine epithelial cells, however, this activity was lost in all truncated peptides. None of the peptides bound LPS and subsequently did not inhibit LPS-induced cytokine production of monocytes. Finally, all PMAP-23 derived peptides reduced the uptake of beads by freshly isolated monocytes.PMAP-23 is mainly antibacterial with only limited immunomodulating capacity; the full length peptide is required for the full spectrum of activities.

Antibacterial peptide

10.2174/0929866524666170428150925

Cite

Citations (27)

Antimicrobial and Immunomodulatory Activities of PR-39 Derived Peptides

PLoS ONE (2014)

Edwin J.A. Veldhuizen Viktoria A. F. Schneider Herfita Agustiandari Albert van Dijk Johanna L. M. Tjeerdsma-van Bokhoven

The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal) amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics.

Cathelicidin

Beta defensin

Enterococcus faecalis

10.1371/journal.pone.0095939

Cite

Citations (112)

The β-Defensin Gallinacin-6 Is Expressed in the Chicken Digestive Tract and Has Antimicrobial Activity against Food-Borne Pathogens

Antimicrobial Agents and Chemotherapy (2006)

Albert van Dijk Edwin J.A. Veldhuizen Stefanie I. C. Kalkhove Johanna L. M. Tjeerdsma-van Bokhoven Roland A. Romijn

Food-borne pathogens are responsible for most cases of food poisoning in developed countries and are often associated with poultry products, including chicken. Little is known about the role of beta-defensins in the chicken digestive tract and their efficacy. In this study, the expression of chicken beta-defensin gallinacin-6 (Gal-6) and its antimicrobial activity against food-borne pathogens were investigated. Reverse transcription-PCR analysis showed high expression of Gal-6 mRNA in the esophagus and crop, moderate expression in the glandular stomach, and low expression throughout the intestinal tract. Putative transcription factor binding sites for nuclear factor kappa beta, activator protein 1, and nuclear factor interleukin-6 were found in the Gal-6 gene upstream region, which suggests a possible inducible nature of the Gal-6 gene. In colony-counting assays, strong bactericidal and fungicidal activity was observed, including bactericidal activity against food-borne pathogens Campylobacter jejuni, Salmonella enterica serovar Typhimurium, Clostridium perfringens, and Escherichia coli. Treatment with 16 mug/ml synthetic Gal-6 resulted in a 3 log unit reduction in Clostridium perfringens survival within 60 min, indicating fast killing kinetics. Transmission electron microscopy examination of synthetic-Gal-6-treated Clostridium perfringens cells showed dose-dependent changes in morphology after 30 min, including intracellular granulation, cytoplasm retraction, irregular septum formation in dividing cells, and cell lysis. The high expression in the proximal digestive tract and broad antimicrobial activity suggest that chicken beta-defensin gallinacin-6 plays an important role in chicken innate host defense.

Clostridium perfringens

Salmonella enterica

10.1128/aac.00568-06

Cite

Citations (134)

Campylobacter jejuni is highly susceptible to killing by chicken host defense peptide cathelicidin-2 and suppresses intestinal cathelicidin-2 expression in young broilers

Veterinary Microbiology (2012)

Albert van Dijk Maaike Herrebout Monique H.G. Tersteeg‐Zijderveld Johanna L. M. Tjeerdsma-van Bokhoven Nancy M. C. Bleumink‐Pluym

Salmonella enteritidis

Cathelicidin

10.1016/j.vetmic.2012.05.034

Cite

Citations (31)