Title |
Phenotypic and genotypic correlates of daptomycin-resistant methicillin-susceptible Staphylococcus aureus clinical isolates |
Author |
Kyoung-Mi Kang1, Nagendra N. Mishra2,3, Kun Taek Park4, Gi-Yong Lee1, Yong Ho Park4, Arnold S. Bayer2,3, and Soo-Jin Yang1* |
Address |
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 Korea |
Bibliography |
Journal of Microbiology, 55(2),153-159, 2017,
|
DOI |
10.1007/s12275-017-6509-1
|
Key Words |
Staphylococcus aureus, daptomycin resistance,
mprF, single nucleotide polymorphism (SNP), host defense
antimicrobial peptide |
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. |