Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Structural basis for HflXr-mediated antibiotic resistance in Listeria monocytogenes

TO. Koller, KJ. Turnbull, K. Vaitkevicius, C. Crowe-McAuliffe, M. Roghanian, O. Bulvas, JA. Nakamoto, T. Kurata, C. Julius, GC. Atkinson, J. Johansson, V. Hauryliuk, DN. Wilson

. 2022 ; 50 (19) : 11285-11300. [pub] 2022Oct28

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22032964

HflX is a ubiquitous bacterial GTPase that splits and recycles stressed ribosomes. In addition to HflX, Listeria monocytogenes contains a second HflX homolog, HflXr. Unlike HflX, HflXr confers resistance to macrolide and lincosamide antibiotics by an experimentally unexplored mechanism. Here, we have determined cryo-EM structures of L. monocytogenes HflXr-50S and HflX-50S complexes as well as L. monocytogenes 70S ribosomes in the presence and absence of the lincosamide lincomycin. While the overall geometry of HflXr on the 50S subunit is similar to that of HflX, a loop within the N-terminal domain of HflXr, which is two amino acids longer than in HflX, reaches deeper into the peptidyltransferase center. Moreover, unlike HflX, the binding of HflXr induces conformational changes within adjacent rRNA nucleotides that would be incompatible with drug binding. These findings suggest that HflXr confers resistance using an allosteric ribosome protection mechanism, rather than by simply splitting and recycling antibiotic-stalled ribosomes.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22032964
003      
CZ-PrNML
005      
20241008084004.0
007      
ta
008      
230120s2022 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/nar/gkac934 $2 doi
035    __
$a (PubMed)36300626
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Koller, Timm O $u Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
245    10
$a Structural basis for HflXr-mediated antibiotic resistance in Listeria monocytogenes / $c TO. Koller, KJ. Turnbull, K. Vaitkevicius, C. Crowe-McAuliffe, M. Roghanian, O. Bulvas, JA. Nakamoto, T. Kurata, C. Julius, GC. Atkinson, J. Johansson, V. Hauryliuk, DN. Wilson
520    9_
$a HflX is a ubiquitous bacterial GTPase that splits and recycles stressed ribosomes. In addition to HflX, Listeria monocytogenes contains a second HflX homolog, HflXr. Unlike HflX, HflXr confers resistance to macrolide and lincosamide antibiotics by an experimentally unexplored mechanism. Here, we have determined cryo-EM structures of L. monocytogenes HflXr-50S and HflX-50S complexes as well as L. monocytogenes 70S ribosomes in the presence and absence of the lincosamide lincomycin. While the overall geometry of HflXr on the 50S subunit is similar to that of HflX, a loop within the N-terminal domain of HflXr, which is two amino acids longer than in HflX, reaches deeper into the peptidyltransferase center. Moreover, unlike HflX, the binding of HflXr induces conformational changes within adjacent rRNA nucleotides that would be incompatible with drug binding. These findings suggest that HflXr confers resistance using an allosteric ribosome protection mechanism, rather than by simply splitting and recycling antibiotic-stalled ribosomes.
650    12
$a Listeria monocytogenes $x genetika $7 D008089
650    _2
$a proteiny vázající GTP $x genetika $7 D019204
650    _2
$a antibiotická rezistence $7 D004352
650    _2
$a ribozomy $x genetika $x metabolismus $7 D012270
650    _2
$a linkosamidy $x farmakologie $7 D055231
650    _2
$a antibakteriální látky $x farmakologie $x metabolismus $7 D000900
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Turnbull, Kathryn J $u Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden $u Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen, Denmark
700    1_
$a Vaitkevicius, Karolis $u Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden
700    1_
$a Crowe-McAuliffe, Caillan $u Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
700    1_
$a Roghanian, Mohammad $u Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden $u Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen, Denmark $u Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden
700    1_
$a Bulvas, Ondřej $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nam. 2, 166 10 Prague 6, Czech Republic $u Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague 6, Czech Republic $7 xx0323147
700    1_
$a Nakamoto, Jose A $u Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden
700    1_
$a Kurata, Tatsuaki $u Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden $u Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden
700    1_
$a Julius, Christina $u Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden
700    1_
$a Atkinson, Gemma C $u Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden
700    1_
$a Johansson, Jörgen $u Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden
700    1_
$a Hauryliuk, Vasili $u Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden $u Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden $u University of Tartu, Institute of Technology, 50411 Tartu, Estonia $1 https://orcid.org/0000000323895057
700    1_
$a Wilson, Daniel N $u Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany $1 https://orcid.org/0000000338163828
773    0_
$w MED00003554 $t Nucleic acids research $x 1362-4962 $g Roč. 50, č. 19 (2022), s. 11285-11300
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36300626 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230120 $b ABA008
991    __
$a 20241008084000 $b ABA008
999    __
$a ok $b bmc $g 1891622 $s 1184299
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2022 $b 50 $c 19 $d 11285-11300 $e 2022Oct28 $i 1362-4962 $m Nucleic acids research $n Nucleic Acids Res $x MED00003554
LZP    __
$a Pubmed-20230120

Find record

Citation metrics

Archiving options