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MRSA Isolates from Patients with Persistent Bacteremia Generate Nonstable Small Colony Variants In Vitro within Macrophages and Endothelial Cells during Prolonged Vancomycin Exposure.

Publication ,  Journal Article
Fauerharmel-Nunes, T; Flannagan, RS; Goncheva, MI; Bayer, AS; Fowler, VG; Chan, LC; Yeaman, MR; Xiong, YQ; Heinrichs, DE
Published in: Infect Immun
January 24, 2023

Staphylococcus aureus (especially methicillin-resistant S. aureus [MRSA]) is frequently associated with persistent bacteremia (PB) during vancomycin therapy despite consistent susceptibility in vitro. Strategic comparisons of PB strains versus those from vancomycin-resolving bacteremia (RB) would yield important mechanistic insights into PB outcomes. Clinical PB versus RB isolates were assessed in vitro for intracellular replication and small colony variant (SCV) formation within macrophages and endothelial cells (ECs) in the presence or absence of exogenous vancomycin. In both macrophages and ECs, PB and RB isolates replicated within lysosome-associated membrane protein-1 (LAMP-1)-positive compartments. PB isolates formed nonstable small colony variants (nsSCVs) in vancomycin-exposed host cells at a significantly higher frequency than matched RB isolates (in granulocyte-macrophage colony-stimulating factor [GM-CSF], human macrophages PB versus RB, P < 0.0001 at 48 h; in ECs, PB versus RB, P < 0.0001 at 24 h). This phenotype could represent one potential basis for the unique ability of PB isolates to adaptively resist vancomycin therapy and cause PB in humans. Elucidating the molecular mechanism(s) by which PB strains form nsSCVs could facilitate the discovery of novel treatment strategies to mitigate PB due to MRSA.

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Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

January 24, 2023

Volume

91

Issue

1

Start / End Page

e0042322

Location

United States

Related Subject Headings

  • Vancomycin
  • Staphylococcal Infections
  • Microbiology
  • Microbial Sensitivity Tests
  • Methicillin-Resistant Staphylococcus aureus
  • Methicillin Resistance
  • Macrophages
  • Humans
  • Endothelial Cells
  • Bacteremia
 

Citation

APA
Chicago
ICMJE
MLA
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Fauerharmel-Nunes, T., Flannagan, R. S., Goncheva, M. I., Bayer, A. S., Fowler, V. G., Chan, L. C., … Heinrichs, D. E. (2023). MRSA Isolates from Patients with Persistent Bacteremia Generate Nonstable Small Colony Variants In Vitro within Macrophages and Endothelial Cells during Prolonged Vancomycin Exposure. Infect Immun, 91(1), e0042322. https://doi.org/10.1128/iai.00423-22
Fauerharmel-Nunes, Thiago, Ronald S. Flannagan, Mariya I. Goncheva, Arnold S. Bayer, Vance G. Fowler, Liana C. Chan, Michael R. Yeaman, Yan Q. Xiong, and David E. Heinrichs. “MRSA Isolates from Patients with Persistent Bacteremia Generate Nonstable Small Colony Variants In Vitro within Macrophages and Endothelial Cells during Prolonged Vancomycin Exposure.Infect Immun 91, no. 1 (January 24, 2023): e0042322. https://doi.org/10.1128/iai.00423-22.
Fauerharmel-Nunes T, Flannagan RS, Goncheva MI, Bayer AS, Fowler VG, Chan LC, et al. MRSA Isolates from Patients with Persistent Bacteremia Generate Nonstable Small Colony Variants In Vitro within Macrophages and Endothelial Cells during Prolonged Vancomycin Exposure. Infect Immun. 2023 Jan 24;91(1):e0042322.
Fauerharmel-Nunes, Thiago, et al. “MRSA Isolates from Patients with Persistent Bacteremia Generate Nonstable Small Colony Variants In Vitro within Macrophages and Endothelial Cells during Prolonged Vancomycin Exposure.Infect Immun, vol. 91, no. 1, Jan. 2023, p. e0042322. Pubmed, doi:10.1128/iai.00423-22.
Fauerharmel-Nunes T, Flannagan RS, Goncheva MI, Bayer AS, Fowler VG, Chan LC, Yeaman MR, Xiong YQ, Heinrichs DE. MRSA Isolates from Patients with Persistent Bacteremia Generate Nonstable Small Colony Variants In Vitro within Macrophages and Endothelial Cells during Prolonged Vancomycin Exposure. Infect Immun. 2023 Jan 24;91(1):e0042322.

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

January 24, 2023

Volume

91

Issue

1

Start / End Page

e0042322

Location

United States

Related Subject Headings

  • Vancomycin
  • Staphylococcal Infections
  • Microbiology
  • Microbial Sensitivity Tests
  • Methicillin-Resistant Staphylococcus aureus
  • Methicillin Resistance
  • Macrophages
  • Humans
  • Endothelial Cells
  • Bacteremia