Open AccessIncreased Cell Wall Teichoic Acid Production and D-alanylation Are Common Phenotypes among Daptomycin-Resistant Methicillin-Resistant Staphylococcus aureus (MRSA) Clinical Isolates
Author(s) -
Ute Bertsche,
Soo-Jin Yang,
Daniel Kuehner,
Stefanie Wanner,
Nagendra N. Mishra,
Tobias Roth,
Mulugeta Nega,
Alexander Schneider,
Christoph Mayer,
Timo Grau,
Arnold S. Bayer,
Christopher Weidenmaier
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0067398
Subject(s) - teichoic acid , daptomycin , staphylococcus aureus , microbiology and biotechnology , phenotype , biology , staphylococcal infections , methicillin resistant staphylococcus aureus , gene , bacteria , vancomycin , genetics
Multiple mechanisms have been correlated with daptomycin-resistance ( DAP-R ) in Staphylococcus aureus . However, one common phenotype observed in many DAP-R S . Aureus strains is a thickened cell wall (CW). The first evidence for an impact of CW-linked glycopolymers on this phenotype was recently demonstrated in a single, well-characterized DAP-R methicillin-susceptible S. aureus ( MSSA ) strain. In this isolate the thickened CW phenotype was linked to an increased production and D-alanylation of wall teichoic acids (WTA). In the current report, we extended these observations to methicillin-resistant daptomycin-sensitive/daptomyin-resistant ( DAP-S/DAP-R ) strain-pairs. These pairs included methicillin-resistant S. aureus ( MRSA ) isolates with and without single nucleotide polymorphisms (SNPs) in mprF (a genetic locus linked to DAP-R phenotype). We found increased CW dry mass in all DAP-R vs DAP-S isolates. This correlated with an increased expression of the WTA biosynthesis gene tagA , as well as an increased amount of WTA in the DAP-R vs DAP-S isolates. In addition, all DAP-R isolates showed a higher proportion of WTA D-alanylation vs their corresponding DAP-S isolate. We also detected an increased positive surface charge amongst the DAP-R strains (presumably related to the enhanced D-alanylation). In comparing the detailed CW composition of all isolate pairs, substantive differences were only detected in one DAP-S/DAP-R pair. The thickened CW phenotype, together with an increased surface charge most likely contributes to either: i) a charge-dependent repulsion of calcium complexed-DAP; and/or ii) steric-limited access of DAP to the bacterial cell envelope target. Taken together well-defined perturbations of CW structural and functional metrics contribute to the DAP-R phenotype and are common phenotypes in DAP-R S . Aureus isolates, both MSSA and MRSA. Note: Although “daptomycin-nonsusceptibility” is the generally accepted terminology, we have utilized the term “daptomycin resistance” for ease of presentation in this manuscript