The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Staphylococcus aureus Resistance to Human Defensins and Evasion of Neutrophil Killing via the Novel Virulence Factor Mprf Is Based on Modification of Membrane Lipids with l-Lysine
Open accessAbstract
Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
Cited by
Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?
Brogden, K. A. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1098 · Cited by 5,829
Defensins: antimicrobial peptides of innate immunity
Ganz, T. (2003) · Nature Reviews Immunology · doi:10.1038/nri1180 · Cited by 3,066
The role of nasal carriage in Staphylococcus aureus infections
Wertheim, H. F., Melles, D. C., Vos, M. C., van Leeuwen, W., van Belkum, A., Verbrugh, H. A., & Nouwen, J. L. (2005) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(05)70295-4 · Cited by 2,685
Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis
Ong, P. Y., Ohtake, T., Brandt, C., Strickland, I., Boguniewicz, M., Ganz, T., Gallo, R. L., & Leung, D. Y. M. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa021481 · Cited by 1,960
Kong, H. H., Oh, J., Deming, C., Conlan, S., Grice, E. A., Beatson, M. A., Nomicos, E., Polley, E. C., Komarow, H. D., Program, N. C. S., et al. (2012) · Genome Research · doi:10.1101/gr.131029.111 · Cited by 1,808
Membrane lipid homeostasis in bacteria
Zhang, Y.-M., & Rock, C. O. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1839 · Cited by 1,393
Antimicrobial mechanisms of phagocytes and bacterial evasion strategies
Flannagan, R. S., Cosío, G., & Grinstein, S. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2128 · Cited by 947
Lai, Y., Cogen, A. L., Radek, K. A., Park, H. J., MacLeod, D. T., Leichtle, A., Ryan, A. F., Di Nardo, A., & Gallo, R. L. (2010) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.123 · Cited by 446
Neutrophils in innate host defense against Staphylococcus aureus infections
Rigby, K. M., & DeLeo, F. R. (2012) · Seminars in Immunopathology · doi:10.1007/s00281-011-0295-3 · Cited by 400
Cosgrove, K., Coutts, G., Jonsson, I.-M., Tarkowski, A., Kokai-Kun, J. F., Mond, J. J., & Foster, S. J. (2007) · Journal of Bacteriology · doi:10.1128/jb.01524-06 · Cited by 334
Self-citationYeast viral killer toxins: lethality and self-protection
Schmitt, M. J., & Breinig, F. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1347 · Cited by 314
Natural roles of antimicrobial peptides in microbes, plants and animals
Maróti, G., Kereszt, A., Kondorosi, É., & Mergaert, P. (2011) · Research in Microbiology · doi:10.1016/j.resmic.2011.02.005 · Cited by 298
Host defense and pathogenesis in Staphylococcus aureus infections
DeLeo, F. R., Diep, B. A., & Otto, M. (2009) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2008.10.003 · Cited by 269
“ing binding of cationic AMPs, and they are encoded by the dlt operon and the mprF locus, respectively.(71,72) Furthermore, expression of the VraFG transporter is increased upon AMP exposure.”
BackgroundSelf-citationThe Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin
Clarke, S. R., Mohamed, R., Bian, L., Routh, A. F., Kokai-Kun, J. F., Mond, J. J., Tarkowski, A., & Foster, S. J. (2007) · Cell Host & Microbe · doi:10.1016/j.chom.2007.04.005 · Cited by 225
Self-citationMetal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity
Cassat, J. E., & Skaar, E. P. (2012) · Seminars in Immunopathology · doi:10.1007/s00281-011-0294-4 · Cited by 155
Palazzolo-Ballance, A. M., Reniere, M. L., Braughton, K. R., Sturdevant, D. E., Otto, M., Kreiswirth, B. N., Skaar, E. P., & DeLeo, F. R. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.1.500 · Cited by 142
Self-citationWerth, B. J., Sakoulas, G., Rose, W. E., Pogliano, J., Tewhey, R., & Rybak, M. J. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01586-12 · Cited by 134
In or out: Phagosomal escape of Staphylococcus aureus
Moldovan, A., & Fraunholz, M. J. (2019) · Cellular Microbiology · doi:10.1111/cmi.12997 · Cited by 106
Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria
Casaburi, G., Duar, R. M., Vance, D. P., Mitchell, R., Contreras, L., Frese, S. A., Smilowitz, J. T., & Underwood, M. A. (2019) · Antimicrobial Resistance & Infection Control · doi:10.1186/s13756-019-0583-6 · Cited by 101
Bactericidal activity of mouse α-defensin cryptdin-4 predominantly affects noncommensal bacteria
Masuda, K., Sakai, N., Nakamura, K., Yoshioka, S., & Ayabe, T. (2011) · Journal of Innate Immunity · doi:10.1159/000322037 · Cited by 94
Ernst, C. M., Kuhn, S., Slavetinsky, C. J., Krismer, B., Heilbronner, S., Gekeler, C., Kraus, D., Wagner, S., & Peschel, A. (2015) · mBio · doi:10.1128/mbio.02340-14 · Cited by 71
Self-citationCryo‐EM structures of multiple‐peptide resistance factor ( MprF ) from Pseudomonas aeruginosa
Jha, S., & Vinothkumar, K. R. (2026) · The FEBS Journal · doi:10.1111/febs.70519 · Cited by 1
Metadata
- Authors
- Peschel, A., Jack, R. W., Otto, M., Collins, L. V., Staubitz, P., Nicholson, G., Kalbacher, H., Nieuwenhuizen, W. F., Jung, G., Tarkowski, A., van Kessel, K. P. M., & van Strijp, J. A. G.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2001-05-07
- Volume
- 193
- Issue
- 9
- Pages
- 1067-1076
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2166791780
- Cited by
- 786
- References
- 1
- FWCI
- 18.38
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
