Phenotypic and genotypic correlates of daptomycin-resistant methicillin-susceptible Staphylococcus aureus clinical isolates

Kyoung-Mi Kang; Nagendra N. Mishra; Kun Taek Park; Gi-Yong Lee; Yong Ho Park; Arnold S. Bayer; Soo-Jin Yang

doi:10.1007/s12275-017-6509-1

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Phenotypic and genotypic correlates of daptomycin-resistant methicillin-susceptible Staphylococcus aureus clinical isolates: Kyoung-Mi Kang ¹, Nagendra N. Mishra ^2,3, Kun Taek Park ⁴, Gi-Yong Lee ¹, Yong Ho Park ⁴, Arnold S. Bayer ^2,3, Soo-Jin Yang ¹; Journal of Microbiology 2017;55(2):153-159.
DOI: https://doi.org/10.1007/s12275-017-6509-1
Published online: January 26, 2017

¹School of Bioresources and Bioscience, Chung-Ang University, Gyeonggi-do 17546, Republic of Korea, ²Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA, ³The David Geffen School of Medicine at UCLA, Los Angeles, California, USA, ⁴Department of Veterinary Microbiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Republic of Korea¹School of Bioresources and Bioscience, Chung-Ang University, Gyeonggi-do 17546, Republic of Korea, ²Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA, ³The David Geffen School of Medicine at UCLA, Los Angeles, California, USA, ⁴Department of Veterinary Microbiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Republic of Korea

Corresponding author: Soo-Jin Yang , Tel: +82-31-670-3256,

Received: 5 October 2016 • Revised: 23 November 2016 • Accepted: 24 November 2016

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Abstract

Daptomycin (DAP) has potent activity in vitro and in vivo against both methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains. DAP-resistance (DAP-R) in S. aureus has been mainly observed in MRSA strains, and has been linked to single nucleotide polymorphisms (SNPs) within the mprF gene leading to altered cell membrane (CM) phospholipid (PL) profiles, enhanced positive surface charge, and changes in CM fluidity. The current study was designed to delineate whether these same genotypic and phenotypic perturbations are demonstrated in clinically-derived DAP-R MSSA strains. We used three isogenic DAP-susceptible (DAP-S)/DAP-R strainpairs and compared: (i) presence of mprF SNPs, (ii) temporal expression profiles of the two key determinants (mprF and dltABCD) of net positive surface charge, (iii) increased production of mprF-dependent lysinylated-phosphatidylglycerol (L-PG), (iv) positive surface charge assays, and (v) susceptibility to cationic host defense peptides (HDPs) of neutrophil and platelet origins. Similar to prior data in MRSA, DAP-R (vs DAP-S) MSSA strains exhibited hallmark hot-spot SNPs in mprF, enhanced and dysregulated expression of both mprF and dltA, L-PG overproduction, HDP resistance and enhanced positive surface charge profiles. However, in contrast to most DAP-R MRSA strains, there were no changes in CM fluidity seen. Thus, charge repulsion via mprF- and dlt-mediated enhancement of positive surface charge may be the main mechanism to explain DAP-R in MSSA strains.

Keywords: Staphylococcus aureus;daptomycin resistance;mprF;single nucleotide polymorphism (SNP);host defense antimicrobial peptide

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Phenotypic and genotypic correlates of daptomycin-resistant methicillin-susceptible Staphylococcus aureus clinical isolates

J. Microbiol. 2017;55(2):153-159. Published online January 26, 2017

DOI: https://doi.org/10.1007/s12275-017-6509-1

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