scholarly journals Evolution and Single-Nucleotide Polymorphisms in Methicillin-Resistant Staphylococcus aureus Strains with Reduced Susceptibility to Vancomycin and Daptomycin, Based on Determination of the Complete Genome

2015 ◽  
Vol 59 (6) ◽  
pp. 3585-3587 ◽  
Author(s):  
Tetsuo Yamaguchi ◽  
Shingo Suzuki ◽  
Sakiko Okamura ◽  
Yuri Miura ◽  
Ayaka Tsukimori ◽  
...  

ABSTRACTWe obtained a series of methicillin-resistantStaphylococcus aureusisolates, including both daptomycin-susceptible strain TD1 and daptomycin-resistant strain TD4, from a patient. We determined the complete genome sequences of TD1 and TD4 using next-generation sequencing, and only four single-nucleotide polymorphisms (SNPs) were identified, one each incapB(E58K),rpoB(H481Y),lytN(I16V), andmprF(V351E). We determined that these four SNPs were sufficient to cause the strains to develop daptomycin, vancomycin, and rifampin resistance.

2015 ◽  
Vol 59 (8) ◽  
pp. 4930-4937 ◽  
Author(s):  
Arnold S. Bayer ◽  
Nagendra N. Mishra ◽  
Liang Chen ◽  
Barry N. Kreiswirth ◽  
Aileen Rubio ◽  
...  

ABSTRACTMprF is responsible for the lysinylation of phosphatidylglycerol (PG) to synthesize the positively charged phospholipid (PL) species, lysyl-PG (L-PG). It has been proposed that the single-nucleotide polymorphisms (SNPs) within themprFopen reading frame (ORF) are associated with a gain-in-function phenotype in terms of daptomycin resistance inStaphylococcus aureus. (Note that although the official term is daptomycin nonsusceptibility, we use the term daptomycin resistance in this paper for ease of presentation.) Using 22 daptomycin-susceptible (DAPs)/daptomycin-resistant (DAPr) clinical methicillin-resistantS. aureus(MRSA) strain pairs, we assessed (i) the frequencies and distribution of putativemprFgain-in-function SNPs, (ii) the relationships of the SNPs to both daptomycin resistance and cross-resistance to the prototypical endovascular host defense peptide (HDP) thrombin-induced platelet microbicidal protein (tPMP), and (iii) the impact ofmprFSNPs on positive surface charge phenotype and modifications of membrane PL profiles. Most of themprFSNPs identified in our DAPrstrains were clustered within the two MprF loci, (i) the central bifunctional domain and (ii) the C-terminal synthase domain. Moreover, we were able to correlate the presence and location ofmprFSNPs in DAPrstrains with HDP cross-resistance, positive surface charge, and L-PG profiles. Although DAPrstrains withmprFSNPs in the bifunctional domain showed higher resistance to tPMPs than DAPrstrains with SNPs in the synthase domain, this relationship was not observed in positive surface charge assays. These results demonstrated that both charge-mediated and -unrelated mechanisms are involved in DAP resistance and HDP cross-resistance inS. aureus.


2013 ◽  
Vol 57 (11) ◽  
pp. 5658-5664 ◽  
Author(s):  
Soo-Jin Yang ◽  
Nagendra N. Mishra ◽  
Aileen Rubio ◽  
Arnold S. Bayer

ABSTRACTSingle nucleotide polymorphisms (SNPs) within themprFopen reading frame (ORF) have been commonly observed in daptomycin-resistant (DAPr)Staphylococcus aureusstrains. Such SNPs are usually associated with a gain-in-function phenotype, in terms of either increased synthesis or enhanced translocation (flipping) of lysyl-phosphatidylglycerol (L-PG). However, it is unclear if suchmprFSNPs are causal in DAPrstrains or are merely a biomarker for this phenotype. In this study, we used an isogenic set ofS. aureusstrains: (i) Newman, (ii) its isogenic ΔmprFmutant, and (iii) several intransplasmid complementation constructs, expressing either a wild-type or point-mutated form of themprFORF cloned from two isogenic DAP-susceptible (DAPs)-DAPrstrain pairs (616-701 and MRSA11/11-REF2145). Complementation of the ΔmprFstrain with singly point-mutatedmprFgenes (mprFS295LormprFT345A) revealed that (i) individual and distinct point mutations within themprFORF can recapitulate phenotypes observed in donor strains (i.e., changes in DAP MICs, positive surface charge, and cell membrane phospholipid profiles) and (ii) these gain-in-function SNPs (i.e., enhanced L-PG synthesis) likely promote reduced DAP binding toS. aureusby a charge repulsion mechanism. Thus, for these two DAPrstrains, the definedmprFSNPs appear to be causally related to this phenotype.


2016 ◽  
Vol 60 (11) ◽  
pp. 6928-6932 ◽  
Author(s):  
Sun Hee Lee ◽  
Wan Beom Park ◽  
Shinwon Lee ◽  
Sohee Park ◽  
Shin Woo Kim ◽  
...  

ABSTRACTSome proportion of type AblaZgene-positive methicillin-susceptibleStaphylococcus aureusstrains exhibit the cefazolin inoculum effect (CIE). The type AblaZgene was divided into two groups by single nucleotide polymorphisms (SNPs) at Ser226Pro and Cys229Tyr. The median cefazolin MICs at a high inoculum concentration were 5.69 μg/ml for the Ser-Cys group and 40.32 μg/ml for the Pro-Tyr group (P= 0.01). The SNPs at codons 226 and 229 in the amino acid sequence encoded by theblaZgene were closely associated with the CIE.


2010 ◽  
Vol 34 (8) ◽  
pp. S75-S75
Author(s):  
Weifeng Zhu ◽  
Zhuoqi Liu ◽  
Daya Luo ◽  
Xinyao Wu ◽  
Fusheng Wan

2013 ◽  
Vol 57 (11) ◽  
pp. 5717-5720 ◽  
Author(s):  
Hung-Jen Tang ◽  
Chi-Chung Chen ◽  
Kuo-Chen Cheng ◽  
Kuan-Ying Wu ◽  
Yi-Chung Lin ◽  
...  

ABSTRACTTo compare thein vitroantibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistantStaphylococcus aureus(MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.


2020 ◽  
Vol 9 (41) ◽  
Author(s):  
Raphael N. Sieber ◽  
Søren Overballe-Petersen ◽  
Hülya Kaya ◽  
Anders R. Larsen ◽  
Andreas Petersen

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) sequence type 630 (ST630) and spa type t4549 is an emerging lineage in Nordic countries, and some representatives carry the CRISPR-Cas system. Here, the complete genome sequences of two isolates from this lineage are presented, comprising chromosomes of 2,918,239 and 2,877,083 nucleotides, respectively, and a 2,473-nucleotide plasmid carrying erm(C).


2017 ◽  
Vol 5 (35) ◽  
Author(s):  
Junzo Hisatsune ◽  
Hideharu Hagiya ◽  
Sumiko Shiota ◽  
Motoyuki Sugai

ABSTRACT Staphylococcus aureus JH4899, a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate collected from a patient with systematically disseminated infection, is classified as sequence type 8 and carries the staphylococcal cassette chromosome mec type IVl (SCCmecIVl). It produces TSST-1, SEC, a newly discovered enterotoxin (SE1), and epidermal cell differentiation inhibitor A (EDIN-A). Here, we present the complete genome sequence of the chromosome and a plasmid harboring the se1 and ednA genes.


2021 ◽  
Vol 10 (37) ◽  
Author(s):  
Nicola M. Karakatsanis ◽  
Shakeel Mowlaboccus ◽  
Elena Colombi ◽  
Julie C. Pearson ◽  
Joshua P. Ramsay ◽  
...  

Sequence type 1 (ST1) methicillin-resistant Staphylococcus aureus (MRSA) type IV[2B] has become one of the most common community-associated MRSA clones in Australia. We report the complete genome sequence of one of the earliest isolated Australian S. aureus ST1-MRSA-IV strains, WBG8287, isolated from an Indigenous Australian patient living in the remote Kimberley Region of Western Australia.


PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18428 ◽  
Author(s):  
Xudong Liang ◽  
Jeffrey W. Hall ◽  
Junshu Yang ◽  
Meiying Yan ◽  
Katherine Doll ◽  
...  

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