Peptide Biomarker Discovery for Identification of Methicillin

*Phone:+886-4-22052121-2761. ... Vancomycin-intermediate S. aureus (VISA) strains are defined as having an MIC of 4–8 ... MS profiling spectra were ...
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Peptide Biomarker Discovery for Identification of Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus Strains by MALDI-TOF Jang-Jih Lu,†,‡ Fuu-Jen Tsai,⊥,§ Cheng-Mao Ho,‡,# Yu-Ching Liu,∇ and Chao-Jung Chen*,∇,∥ †

Department of Laboratory Medicine, Chang-Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan Graduate Institute of Clinical Medical Science, §College of Chinese Medicine, and ∥Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan ⊥ Department of Medical Genetics, Pediatrics and Medical Research, #Department of Laboratory Medicine, and ∇Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan ‡

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ABSTRACT: Rapid identification of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA), hospital-associated (HA) MRSA, and vancomycin-intermediate S. aureus (VISA) is essential for proper therapy and timely intervention of outbreaks. In this study, peptide biomarkers for rapid identification of methicillin-resistant and vancomycinintermediate S. aureus strains were discovered by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results showed that the 1774.1 and 1792.1 m/z peaks corresponding to the phenol-soluble modulin α1 and phenolsoluble modulin α2 peptides, respectively, were present in the majority (95%, 121 of 127) of SCCmec types IV and V isolates, but only in 8% (15 of 185) of SCCmec types I−III isolates. Since SCCmec types I−III isolates are recognized as HA-MRSA and most CA-MRSA isolates belong to SCCmec types IV and V, these two peptides may serve as markers for discrimination between HA-MRSA and CA-MRSA isolates. The 1835.0 and 1863.0 m/z peaks were present in 50% (4 of 8) of heterogeneous VISA and 88% (14 of 16) of VISA isolates. The peptides of these two peaks were identified as proteolytic products of the acyl carrier protein. The results of this study provide the possibility to develop methods for identification of CA-MRSA, HA-MRSA, and vancomycin-resistant S. aureus isolates based on the presence of these peptides.

Staphylococcus aureus, a Gram-positive opportunistic human pathogen, can cause severe infections in cardiovascular, osteoarticular, and respiratory systems as well as in the skin and soft tissues. S. aureus is one of the most common and important pathogens in both community-associated and hospital-associated infections.1 Several evolutions of S. aureus have occurred since the introduction of antibiotics in the 1940s, including the development of resistance to penicillin, methicillin, and vancomycin and the appearance of community-acquired methicillin-resistant S. aureus (MRSA).2 Since the first discovery in the 1960s, the incidence of MRSA nosocomial infection has been increasing,3 and community-associated MRSA (CAMRSA) is considered as an emerging pathogen.2,4 Because the frequent use of glycopeptide antibiotics for treatment of MRSA infections, S. aureus strains with different levels of resistance to vancomycin, such as heterogeneous vancomycin-intermediate S. aureus (hVISA) and vancomycin-resistant S. aureus (VRSA), have emerged within the past 10 years. According to the current criteria of the Clinical and Laboratory Standards Institute (CLSI), S. aureus strains exhibiting a minimum inhibitory concentration (MIC) >2 but