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@ARTICLE{Arad:613873,
author = {Arad, Elad and Pedersen, Kasper B. and Malka, Orit and
Mambram Kunnath, Sisira and Golan, Nimrod and Aibinder,
Polina and Schiøtt, Birgit and Rapaport, Hanna and Landau,
Meytal and Jelinek, Raz},
title = {{S}taphylococcus aureus functional amyloids catalyze
degradation of β-lactam antibiotics},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {PUBDB-2024-05652},
pages = {8198},
year = {2023},
abstract = {Antibiotic resistance of bacteria is considered one of the
most alarming developments in modern medicine. While varied
pathways for bacteria acquiring antibiotic resistance have
been identified, there still are open questions concerning
the mechanisms underlying resistance. Here, we show that
alpha phenol-soluble modulins (PSMαs), functional bacterial
amyloids secreted by Staphylococcus aureus, catalyze
hydrolysis of β-lactams, a prominent class of antibiotic
compounds. Specifically, we show that PSMα2 and,
particularly, PSMα3 catalyze hydrolysis of the amide-like
bond of the four membered β-lactam ring of nitrocefin, an
antibiotic β-lactam surrogate. Examination of the catalytic
activities of several PSMα3 variants allowed mapping of the
active sites on the amyloid fibrils’ surface, specifically
underscoring the key roles of the cross-α fibril
organization, and the combined electrostatic and
nucleophilic functions of the lysine arrays. Molecular
dynamics simulations further illuminate the structural
features of β-lactam association upon the fibril surface.
Complementary experimental data underscore the generality of
the functional amyloid-mediated catalytic phenomenon,
demonstrating hydrolysis of clinically employed β-lactams
by PSMα3 fibrils, and illustrating antibiotic degradation
in actual S. aureus biofilms and live bacteria environments.
Overall, this study unveils functional amyloids as catalytic
agents inducing degradation of β-lactam antibiotics,
underlying possible antibiotic resistance mechanisms
associated with bacterial biofilms.},
cin = {CSSB-F / EMBL},
ddc = {500},
cid = {I:(DE-H253)CSSB-F-20230420 / I:(DE-H253)EMBL-20120731},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38081813},
UT = {WOS:001142897900014},
doi = {10.1038/s41467-023-43624-1},
url = {https://bib-pubdb1.desy.de/record/613873},
}