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Heterogeneity of mprF sequences in methicillin-resistant Staphylococcus aureus clinical isolates: role in cross-resistance between daptomycin and host defense antimicrobial peptides

Bayer, Arnold S ; Mishra, Nagendra N ; Sakoulas, George ; Nonejuie, Poochit ; Nast, Cynthia C ; Pogliano, Joseph ; Chen, Kuan-Tsen ; Ellison, Steven N ; Yeaman, Michael R ; Yang, Soo-Jin

Antimicrobial agents and chemotherapy, 2014-12, Vol.58 (12), p.7462-7467 [Periódico revisado por pares]

United States: American Society for Microbiology

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Título:
Heterogeneity of mprF sequences in methicillin-resistant Staphylococcus aureus clinical isolates: role in cross-resistance between daptomycin and host defense antimicrobial peptides
Autor: Bayer, Arnold S ; Mishra, Nagendra N ; Sakoulas, George ; Nonejuie, Poochit ; Nast, Cynthia C ; Pogliano, Joseph ; Chen, Kuan-Tsen ; Ellison, Steven N ; Yeaman, Michael R ; Yang, Soo-Jin
Assuntos: Aminoacyltransferases ; Aminoacyltransferases - genetics ; Aminoacyltransferases - metabolism ; Anti-Bacterial Agents ; Anti-Bacterial Agents - pharmacology ; Antimicrobial Cationic Peptides - pharmacology ; Bacterial Proteins ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Cell Wall - chemistry ; Cell Wall - drug effects ; Cell Wall - metabolism ; Clone Cells ; Daptomycin - pharmacology ; Drug Resistance, Multiple, Bacterial - genetics ; Gene Expression Regulation, Bacterial ; Humans ; Mechanisms of Resistance ; Methicillin-Resistant Staphylococcus aureus ; Methicillin-Resistant Staphylococcus aureus - drug effects ; Methicillin-Resistant Staphylococcus aureus - genetics ; Methicillin-Resistant Staphylococcus aureus - isolation & purification ; Methicillin-Resistant Staphylococcus aureus - metabolism ; Microbial Sensitivity Tests ; Phospholipids - chemistry ; Phospholipids - metabolism ; Polymorphism, Single Nucleotide ; Staphylococcal Infections - microbiology ; Staphylococcus aureus
É parte de: Antimicrobial agents and chemotherapy, 2014-12, Vol.58 (12), p.7462-7467
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Over the past several years, single-nucleotide polymorphisms (SNPs) within the mprF open reading frame (ORF) have been proposed to be associated with a gain-of-function phenotype in terms of daptomycin (DAP) nonsusceptibility (referred to as daptomycin resistance [DAP-R] herein for ease of presentation) in Staphylococcus aureus. We investigated the frequencies of SNPs within the mprF ORF and the relationships of such SNPs to cross-resistance between DAP and cationic host defense peptides (HDPs). Thirty-five well-characterized, unique DAP-susceptible (DAP-S) and DAP-R methicillin-resistant S. aureus (MRSA) isolates of the clonal complex 5 genotype were used. In addition to mprF SNPs and DAP-HDP cross-resistance, several other key genotypic and phenotypic metrics often associated with DAP-R were delineated, as follows: (i) mprF expression, (ii) membrane phospholipid content, (iii) positive surface charge, (iv) DAP binding, and (v) cell wall thickness profiles. A number of DAP-S strains (MICs of ≤ 1 μg/ml) exhibited mprF SNPs, occasionally with high-level mprF sequence variation from the genotype reference strain. However, none of these SNPs were localized to well-chronicled mprF hot spot locations associated with DAP-R in S. aureus. In contrast, all 8 DAP-R isolates demonstrated SNPs within such known mprF hot spots. Moreover, only the DAP-R strains showed MprF gain-of-function phenotypes, enhanced mprF expression, higher survival against two prototypical HDPs, and reduced DAP binding. Although a heterogenous array of mprF SNPs were often found in DAP-S strains, only selected hot spot SNPs, combined with concurrent mprF dysregulation, were associated with the DAP-R phenotype.
Editor: United States: American Society for Microbiology
Idioma: Inglês

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Heterogeneity of mprF sequences in methicillin-resistant Staphylococcus aureus clinical isolates: role in cross-resistance between daptomycin and host defense antimicrobial peptides

Bayer, Arnold S ; Mishra, Nagendra N ; Sakoulas, George ; Nonejuie, Poochit ; Nast, Cynthia C ; Pogliano, Joseph ; Chen, Kuan-Tsen ; Ellison, Steven N ; Yeaman, Michael R ; Yang, Soo-Jin

United States: American Society for Microbiology

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