Novel Determinants of Antibiotic Resistance: Identification of Mutated Loci in Highly Methicillin-Resistant Subpopulations of Methicillin-Resistant Staphylococcus aureus

Dordel, Janina; Kim, Choon; Chung, Marilyn; Gándara, María Pardos de la; Holden, Matthew T. G.; Parkhill, Julian; Lencastre, Herminia Garcez; Bentley, Stephen D.; Tomasz, Alexander

doi:10.1128/mbio.01000-13

Cited by 76 publications

(114 citation statements)

References 46 publications

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“…Heterogeneously resistant MRSA strains were converted to H*R mutants, which showed homogeneous and high-level antibiotic resistance associated with a variety of different mutations (11,12). A major result of this study was identification of the relA gene and the stringent stress response as critical contributors to the resistance phenotypes of MRSA strains (11)(12)(13)(14).…”

mentioning

confidence: 90%

“…Titration of PBP 2A on the plasma membrane. Membrane fractions were prepared from S. aureus COL and its auxiliary mutant derivatives, according to the method described previously (12). The strains were grown in 200 ml of TSB with and without 0.03 g/ml mupirocin at 37°C.…”

Section: Susceptibility Of Auxiliary Mutants To Oxacillinmentioning

confidence: 99%

“…Based on the comparison of 27 mutated genes in H*R mutants with those identified in strain COL, it was possible to show that COL carried mutations in four genes relevant for the resistance phenotype: in prsA (ribose-phosphate pyrophosphokinase), in gltX (glutamyl-tRNA synthetase), in rplK (ribosomal protein L11), and in rpoB (the ␤-subunit of DNA-directed RNA polymerase) (12). Strain COL also exhibits slow growth, which is a typical phenotype of bacteria under stress.…”

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confidence: 99%

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Antibiotic Resistance as a Stress Response: Recovery of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus “Auxiliary” ( fem ) Mutants by Induction of the Stringent Stress Response

Kim

Milheiriço

Lencastre

et al. 2017

Antimicrob Agents Chemother

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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).

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mentioning

confidence: 90%

Section: Susceptibility Of Auxiliary Mutants To Oxacillinmentioning

confidence: 99%

mentioning

confidence: 99%

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Antibiotic Resistance as a Stress Response: Recovery of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus “Auxiliary” ( fem ) Mutants by Induction of the Stringent Stress Response

Kim

Milheiriço

Lencastre

et al. 2017

Antimicrob Agents Chemother

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“…Invasive and colonizing isolates from three patients that were characterized by whole-genome sequencing were also characterized for their oxacillin resistance phenotypes by population analysis profiles (PAPs) (27,28).…”

Section: Methodsmentioning

confidence: 99%

Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization, Identified in Community Health Centers in New York City

et al. 2015

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Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquired Staphylococcus aureus strains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious for S. aureus were collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected by S. aureus: methicillinresistant S. aureus (MRSA) was recovered from 39 wounds and methicillin-sensitive S. aureus (MSSA) was recovered from 24. Most-46 of the 63-wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL ؉ ) group of S. aureus clone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients with S. aureus infections, 30 were also colonized by S. aureus in the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing. Staphylococcus aureus is the most common cause of bacterial infections in humans worldwide (1), and methicillin-resistant Staphylococcus aureus (MRSA) is the main cause of skin and soft tissue infections (SSTIs) in North America, with a single clone, USA300, accounting for 98% of these infections (2, 3).The first human case of MRSA infection in the United States was reported in Boston, MA, in 1968 (4). MRSA was first detected in hospitals, and over the following decades, it became the main nosocomial pathogen around the world (5). In 1998, the prevalence of MRSA in 12 hospitals throughout the city of New York was assessed (6), and a single MRSA clone was found to be responsible for an overwhelming majority of MRSA infections. The same MRSA clone was subsequently identified as dominant in MRSA infections in 29 hospitals in the tristate area (7), and it was also identified in MRSA infections in Japan (8). This MRSA clone (multilocus sequence typing [MLST] clonal complex CC5, sequence type ST5, SCCmecII, and unique pulsed-field gel electrophoresis [PFGE] profile)-also known as the "New York/Japan clone" or "MRSA clone USA100"-became the most prevalent MRSA clone involved in MRSA infections in hospitals in the United States in the 1990s (9).In 1993, a new MRSA clone emerged in Kimberley, Western Australia (10), in a community of patients without previous health care contact (community-acquired MRSA [CA-MRSA]). In the late 1990s, CA-MRSA also appeared in the United States and was responsible for the death of four otherwise healthy pediatric patients in Minnesota and North Dakota (11). These new CA-MRSA strains belonged to a clone (USA400/CC1/SCCmecIV)

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“…Estos elementos están formados por el gen mecA, elementos reguladores y la recombinasa cromosomal del cassette (ccr), la que se relaciona la integración/escisión sitio-específica de este elemento 60,61 . En este estudio, 3/11 cepas positivas al gen mecA fueron susceptibles a meticilina, lo que se puede explicar por la existencia de cuatro clases de expresión fenotípica de resistencia a este antimicrobiano en S. aureus 62,63 .…”

Section: Artículo Originalunclassified

Detección del gen mecA en cepas de Staphylococcus coagulasa positiva aisladas desde gatos

Galarce

Muñoz

Jara

et al. 2016

Rev. chil. infectol.

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Novel Determinants of Antibiotic Resistance: Identification of Mutated Loci in Highly Methicillin-Resistant Subpopulations of Methicillin-Resistant Staphylococcus aureus

Cited by 76 publications

References 46 publications

Antibiotic Resistance as a Stress Response: Recovery of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus “Auxiliary” ( fem ) Mutants by Induction of the Stringent Stress Response

Antibiotic Resistance as a Stress Response: Recovery of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus “Auxiliary” ( fem ) Mutants by Induction of the Stringent Stress Response

Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization, Identified in Community Health Centers in New York City

Detección del gen mecA en cepas de Staphylococcus coagulasa positiva aisladas desde gatos

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