scholarly journals Emergence of Oxacillin Resistance in Stealth Methicillin-Resistant Staphylococcus aureus Due to mecA Sequence Instability

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Richard V. Goering ◽  
Erin A. Swartzendruber ◽  
Anne E. Obradovich ◽  
Isabella A. Tickler ◽  
Fred C. Tenover

ABSTRACT Staphylococcus aureus strains that possess a mecA gene but are phenotypically susceptible to oxacillin and cefoxitin (OS-MRSA) have been recognized for over a decade and are a challenge for diagnostic laboratories. The mechanisms underlying the discrepancy vary from isolate to isolate. We characterized seven OS-MRSA clinical isolates of six different spa types from six different states by whole-genome sequencing to identify the nucleotide sequence changes leading to the OS-MRSA phenotype. The results demonstrated that oxacillin susceptibility was associated with mutations in regions of nucleotide repeats within mecA. Subinhibitory antibiotic exposure selected for secondary mecA mutations that restored oxacillin resistance. Thus, strains of S. aureus that contain mecA but are phenotypically susceptible can become resistant after antibiotic exposure, which may result in treatment failure. OS-MRSA warrant follow-up susceptibility testing to ensure detection of resistant revertants.

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Choon Keun Kim ◽  
Catarina Milheiriço ◽  
Hermínia de Lencastre ◽  
Alexander Tomasz

ABSTRACT Studies with methicillin-resistant Staphylococcus aureus (MRSA) strain COL have shown that the optimal resistance phenotype requires not only mecA but also a large number of “auxiliary genes” identified by Tn551 mutagenesis. The majority of auxiliary mutants showed greatly increased levels of oxacillin resistance when grown in the presence of sub-MICs of mupirocin, suggesting that the mechanism of reduced resistance in the auxiliary mutants involved the interruption of a stringent stress response, causing reduced production of penicillin-binding protein 2A (PBP 2A).


2013 ◽  
Vol 57 (11) ◽  
pp. 5774-5777 ◽  
Author(s):  
Artur J. Sabat ◽  
Robin Köck ◽  
Viktoria Akkerboom ◽  
Ron Hendrix ◽  
Robert L. Skov ◽  
...  

ABSTRACTIn this study, 425 methicillin-resistantStaphylococcus aureus(MRSA) isolates recovered in the Dutch-German Euregio were investigated for the presence of the arginine catabolic mobile element (ACME). Sequence analysis by whole-genome sequencing revealed an entirely new organization of the ACME-staphylococcal cassette chromosomemeccomposite island (SCCmec-CI), with truncated ACME type II located downstream of SCCmec. An identical nucleotide sequence of ACME-SCCmec-CI was found in two distinct MRSA lineages (t064-ST8 and t002-ST5), which has not been reported previously inS. aureus.


2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Xuting Zheng ◽  
Andrew D. Berti ◽  
Sue McCrone ◽  
Melanie Roch ◽  
Adriana E. Rosato ◽  
...  

ABSTRACTInvasive methicillin-resistantStaphylococcus aureus(MRSA) treated with vancomycin (VAN) is associated with reduced VAN susceptibility and treatment failure. VAN combination therapy is one strategy to improve response, but comprehensive assessments of combinations to prevent resistance are limited. This study identifies optimal combinations to prevent the emergence of VAN-intermediateStaphylococcus aureus(VISA). Two standard MRSA and two heterogeneous VISA (hVISA) strains were exposed for 28 daysin vitroto VAN alone, VAN with cefazolin (CFZ), fosfomycin, gentamicin, meropenem, rifampin, piperacillin-tazobactam (TZP), or trimethoprim-sulfamethoxazole. In addition to VAN susceptibility testing, cell wall thickness (CWT), carotenoid content, and membrane fluidity were determined for Mu3. VAN plus any β-lactam limited the VAN MIC increase to 1 to 4 mg/liter throughout the 28-day exposure, with CFZ and TZP being the most effective agents (VAN MIC = 1 to 2 mg/liter). Similar MIC trends occurred with the lipo-/glycopeptide agents daptomycin and telavancin, where β-lactam combinations with VAN prevented MIC increases to these agents as well. Combinations with non-β-lactams were ineffective in preventing VAN MIC increases with VAN MICs of 4 to 16 mg/liter emerging during weeks 2 to 4 of treatment. VAN plus β-lactam decreased CWT significantly, whereas VAN plus other antibiotics significantly increased the CWT. No correlation was observed between carotenoid content or membrane fluidity and antibiotic exposure. Only the combination exposures of VAN plus β-lactam suppress the development of VISA. Rational selection of VAN plus β-lactam should be further explored as a long-term combination treatment of MRSA infections due to their ability to suppress VAN resistance.


2020 ◽  
Vol 58 (4) ◽  
Author(s):  
Ellen N. Kersh ◽  
Cau D. Pham ◽  
John R. Papp ◽  
Robert Myers ◽  
Richard Steece ◽  
...  

ABSTRACT U.S. gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for N. gonorrhoeae identification, the capacity for culturing N. gonorrhoeae in the United States has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet AST is critical for detecting and monitoring AR-Ng. In 2016, the CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up the national capacity for detecting several resistance threats including N. gonorrhoeae. AR-Ng testing, a subactivity of the CDC’s AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in Maryland, Tennessee, Texas, and Washington), and the CDC’s national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and the program Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole-genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 N. gonorrhoeae isolates, respectively, and the CDC received 531 and 646 concerning isolates and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported the laboratory capacity for N. gonorrhoeae AST and associated genetic marker detection, expanding preexisting notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.


2011 ◽  
Vol 55 (5) ◽  
pp. 2466-2468 ◽  
Author(s):  
Yurika Ikeda-Dantsuji ◽  
Hideaki Hanaki ◽  
Taiji Nakae ◽  
Yoshio Takesue ◽  
Kazunori Tomono ◽  
...  

ABSTRACTMethicillin-resistantStaphylococcus aureuswith a MIC of linezolid of 4 μg/ml, isolated from a patient who had undergone unsuccessful linezolid therapy, yielded linezolid-resistant mutants in blood agar at 48 h of incubation. The resistant clones showed a MIC of linezolid ranging from 8 to 64 μg/ml and accumulated the T2500A mutation(s) of the rRNA genes. Emergence of these resistant clones appears to be facilitated by a cryptic mutation or mutations associated with chloramphenicol resistance.


2015 ◽  
Vol 3 (2) ◽  
Author(s):  
Luke T. Daum ◽  
Violet V. Bumah ◽  
Daniela S. Masson-Meyers ◽  
Manjeet Khubbar ◽  
John D. Rodriguez ◽  
...  

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.


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