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Frontiers in cellular and infection microbiology
2024;14 1453233.

Phenotypic and genetic characterization of daptomycin non-susceptible strains selected by adaptive laboratory evolution.

Yanlei Xu, Yanghua Xiao, Huilin Zhao, Bingjie Wang, Jingyi Yu, Yongpeng Shang, Ying Zhou, Xiaocui Wu, Yinjuan Guo, Fangyou Yu
Author Information
  1. Yanlei Xu: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  2. Yanghua Xiao: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  3. Huilin Zhao: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  4. Bingjie Wang: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  5. Jingyi Yu: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  6. Yongpeng Shang: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  7. Ying Zhou: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  8. Xiaocui Wu: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  9. Yinjuan Guo: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  10. Fangyou Yu: Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
PMID: 39512591 DOI: 10.3389/fcimb.2024.1453233

Abstract

Background: Daptomycin non-susceptible (DNS) strains pose a serious clinical threat, yet their characteristics remain poorly understood.
Methods: DNS derivatives were generated by exposing strains to subinhibitory concentrations of daptomycin. Competition experiment and growth kinetics experiment were used to observe the growth of bacteria. larvae and mouse skin abscess models were used to observe the virulence of bacteria. Transmission electron microscopy (TEM), cytochrome C experiment and biofilm formation experiment were used to observe the drug resistance phenotype. And homologous recombination was used to study the role of mutations.
Results: Phenotypic profiling of DNS strains revealed impaired growth, increased cell wall thickness, enhanced biofilm formation, reduced negative surface charge, and attenuated virulence compared to their wild-type strains. Whole genome sequencing identified mutations in , , and in DNS strains. Allelic replacement experiments validated the roles of MprF L341F and Cls2 F60S substitutions in augmenting daptomycin non-susceptibility in Newman. Deletion of in the Newman strain and complementation of in the Newman-DNS strain did not directly alter daptomycin susceptibility. However, the deletion of was found to enhance competitive fitness under daptomycin pressure.
Conclusion: This work validates adaptive laboratory evolution (ALE) for modeling clinical DNS strains and uncovers contributions of , , and mutations to the adaptation and resistance mechanisms of against daptomycin. These findings enrich our understanding of how acquired resistance to daptomycin, thus paving the way for the development of more effective treatment strategies and offering potential molecular markers for resistance surveillance.

Keywords

Staphylococcus aureus daptomycin mprF non-susceptible saeR

References

Microb Drug Resist. 2018 Oct;24(8):1075-1081 [PMID: 29381428]
J Bacteriol. 1972 Feb;109(2):820-6 [PMID: 5058454]
PLoS One. 2014 Sep 16;9(9):e107426 [PMID: 25226591]
Bioinformatics. 2018 Sep 1;34(17):i884-i890 [PMID: 30423086]
Antimicrob Agents Chemother. 2011 Jan;55(1):364-7 [PMID: 20974866]
PLoS Comput Biol. 2017 Jun 8;13(6):e1005595 [PMID: 28594827]
Front Microbiol. 2019 Feb 28;10:345 [PMID: 30891010]
Gene. 1991 Jul 15;103(1):101-5 [PMID: 1652539]
Sci Rep. 2018 Jul 11;8(1):10446 [PMID: 29993029]
Int J Microbiol. 2012;2012:683450 [PMID: 22956961]
J Antimicrob Chemother. 2009 Jul;64(1):151-8 [PMID: 19389714]
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3722-3727 [PMID: 30808758]
J Biol Chem. 1999 Mar 26;274(13):8405-10 [PMID: 10085071]
Appl Environ Microbiol. 2021 Oct 14;87(21):e0103521 [PMID: 34406823]
Ann N Y Acad Sci. 2013 Jan;1277:139-58 [PMID: 23215859]
PLoS Pathog. 2011 Nov;7(11):e1002359 [PMID: 22102812]
Antibiotics (Basel). 2023 May 18;12(5): [PMID: 37237831]
Front Microbiol. 2017 Dec 05;8:2303 [PMID: 29259579]
Infect Immun. 2006 Aug;74(8):4655-65 [PMID: 16861653]
Antimicrob Agents Chemother. 2014 Dec;58(12):7462-7 [PMID: 25288091]
J Antibiot (Tokyo). 2015 Oct;68(10):646-8 [PMID: 25899124]
Antimicrob Agents Chemother. 2011 Aug;55(8):3922-8 [PMID: 21606222]
mBio. 2018 Dec 18;9(6): [PMID: 30563904]
Biotechnol Adv. 2022 Jan-Feb;54:107795 [PMID: 34246744]
Antimicrob Agents Chemother. 2010 Aug;54(8):3079-85 [PMID: 20498310]
Antimicrob Agents Chemother. 2013 Nov;57(11):5658-64 [PMID: 24002096]
Antimicrob Agents Chemother. 2011 Sep;55(9):4012-8 [PMID: 21709105]
PLoS One. 2012;7(1):e28316 [PMID: 22238576]
Nat Med. 2007 Dec;13(12):1405-6 [PMID: 18064027]
PLoS One. 2021 Oct 20;16(10):e0258592 [PMID: 34669727]
Appl Environ Microbiol. 2010 May;76(10):3405-8 [PMID: 20363802]
Mol Microbiol. 2011 Apr;80(2):290-9 [PMID: 21306448]
Antimicrob Agents Chemother. 2003 Apr;47(4):1318-23 [PMID: 12654665]
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6808-14 [PMID: 8041701]
Front Microbiol. 2017 Nov 09;8:2199 [PMID: 29170657]
Antimicrob Agents Chemother. 2009 Jun;53(6):2636-7 [PMID: 19289517]
Virulence. 2015;6(2):127-31 [PMID: 25830650]
Microbiology (Reading). 2004 Sep;150(Pt 9):3025-3033 [PMID: 15347760]
Nat Rev Microbiol. 2011 Jan;9(1):62-75 [PMID: 21164535]
J Infect Dis. 2009 Dec 15;200(12):1916-20 [PMID: 19919306]
J Antimicrob Chemother. 2023 Feb 1;78(2):531-539 [PMID: 36537200]
Eur J Clin Microbiol Infect Dis. 2008 Jun;27(6):433-7 [PMID: 18214559]
J Antimicrob Chemother. 2012 Apr;67(4):928-32 [PMID: 22232512]
J Med Microbiol. 2015 Apr;64(Pt 4):323-334 [PMID: 25670813]
Antimicrob Agents Chemother. 2010 Oct;54(10):4329-34 [PMID: 20696880]
J Bacteriol. 2008 Jan;190(1):300-10 [PMID: 17951380]
PLoS One. 2018 Jun 7;13(6):e0198366 [PMID: 29879195]
Microorganisms. 2021 May 11;9(5): [PMID: 34064631]
J Clin Microbiol. 2006 Feb;44(2):655-6 [PMID: 16455939]
Antimicrob Agents Chemother. 2006 Jun;50(6):2137-45 [PMID: 16723576]
Plasmid. 2006 Jan;55(1):58-63 [PMID: 16051359]

MeSH Term

Daptomycin
Staphylococcus aureus
Animals
Anti-Bacterial Agents
Biofilms
Mice
Phenotype
Staphylococcal Infections
Drug Resistance, Bacterial
Microbial Sensitivity Tests
Mutation
Virulence
Bacterial Proteins
Whole Genome Sequencing
Disease Models, Animal
Larva
Moths
Directed Molecular Evolution
Aminoacyltransferases

Chemicals

Daptomycin
Anti-Bacterial Agents
Bacterial Proteins
mprF protein, Staphylococcus aureus
Aminoacyltransferases
Journal Article

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