Molecular Analysis of Isoleucyl-tRNA Synthetase Mutations in Clinical Isolates of Methicillin-Resistant Staphylococcus aureus with Low-Level Mupirocin Resistance

نویسندگان

  • Jin Ah Yang
  • Dae Won Park
  • Jang Wook Sohn
  • In Seok Yang
  • Kyung Hyun Kim
  • Min Ja Kim
چکیده

Emergence and spread of low-level mupirocin resistance in staphylococci have been increasingly reported in recent years. The aim of this study was to characterize missense mutations within the chromosomal isoleucyl-tRNA synthetase gene (ileS) among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) with low-level mupirocin resistance. A total of 20 isolates of MRSA with low-level mupirocin resistance (minimal inhibitory concentration, 16-64 microg/mL) were collected from 79 patients in intensive care units for six months. The isolates were analyzed for isoleucyl-tRNA synthetase (IleS) mutations that might affect the binding of mupirocin to the three-dimensional structure of the S. aureus IleS enzyme. All isolates with low-level mupirocin resistance contained the known V588F mutation affecting the Rossman fold, and some of them additionally had previously unidentified mutations such as P187F, K226T, F227L, Q612H, or V767D. Interestingly, Q612H was a novel mutation that was involved in stabilizing the conformation of the catalytic loop containing the KMSKS motif. In conclusion, this study confirms that molecular heterogeneity in ileS gene is common among clinical MRSA isolates with low-level mupirocin resistance, and further study on clinical mutants is needed to understand the structural basis of low-level mupirocin resistance.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

شناسایی مقاومت به موپیروسین در سویه‌های استافیلوکوکوس اورئوس جدا شده از بیماران 4 بیمارستان دانشگاهی تهران با روش PCR

  Introduction: Mupirocin, an inhibitor of bacterial isoleucyl-tRNA synthetase, has used to treat staphylococcal skin infections as well as to eliminate nasal carriage of Staphylococcus aureus. Mupirocin resistant Staphylococcus aureus strains are seen worldwide but there is no report from Iran. In the present study, by using phenotyping methods (disk diffusion and E-test) in combination with P...

متن کامل

The isoleucyl-tRNA synthetase mutation V588F conferring mupirocin resistance in glycopeptide-intermediate Staphylococcus aureus is not associated with a significant fitness burden.

OBJECTIVES AND METHODS Failure to eradicate nasal carriage of a glycopeptide-intermediate Staphylococcus aureus (strain GISA-2) with mupirocin was recently attributed to a mutation that confers low-level mupirocin resistance. To identify this mutation the ileS genes of GISA-2 and its mupirocin-susceptible progenitor GISA-1 were sequenced. For comparison, the ileS genes of 10 laboratory-derived ...

متن کامل

MupB, a new high-level mupirocin resistance mechanism in Staphylococcus aureus.

Mupirocin is a topical antibiotic used for the treatment of skin infections and the eradication of methicillin-resistant Staphylococcus aureus carriage. It inhibits bacterial protein synthesis by interfering with isoleucyl-tRNA synthetase activity. High-level mupirocin resistance (MIC of ≥ 512 μg/ml) is mediated by the expression of mupA (ileS2), which encodes an alternate isoleucyl-tRNA synthe...

متن کامل

Prevalence and mechanisms of low- and high-level mupirocin resistance in staphylococci isolated from a Korean hospital.

Mupirocin has been used against Gram-positive pathogenic bacteria, and is a specific inhibitor of bacterial isoleucyl-tRNA synthetase. In this work, we have determined the prevalence of mupirocin resistance among staphylococci isolated from a Korean hospital, and have investigated the characteristics of the resistance. In Staphylococcus aureus, the prevalence of high-level mupirocin resistance ...

متن کامل

Mutations affecting the Rossman fold of isoleucyl-tRNA synthetase are correlated with low-level mupirocin resistance in Staphylococcus aureus.

The isoleucyl-tRNA synthetase (ileS) gene was sequenced in toto from 9 and in part from 31 Staphylococcus aureus strains with various degrees of susceptibility to mupirocin. All strains for which the mupirocin MIC was greater than 8 microg/ml contained point mutations affecting the Rossman fold via Val-to-Phe changes at either residue 588 (V588F) or residue 631 (V631F). The importance of the V5...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 21  شماره 

صفحات  -

تاریخ انتشار 2006