Yu-Tzu Lin1, Jui-Chang Tsai2, Tatsuo Yamamoto3, Hsiao-Jan Chen1, Wei-Chun Hung4, Po-Ren Hsueh5, Lee-Jene Teng6. 1. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan. 2. Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. 3. Department of Epidemiology, Genomics and Evolution, International Medical Education and Research Center, Niigata, Japan. 4. Department of Microbiology and Immunology, Kaohsiung Medical University, Kaohsiung, Taiwan. 5. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 6. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan ljteng@ntu.edu.tw.
Abstract
OBJECTIVES: Small colony variants (SCVs) of Staphylococcus aureus are associated with persistent and drug-resistant infections. We demonstrated for the first time the emergence of SCVs in a patient with vancomycin-intermediate S. aureus (VISA) infection during long-term treatment with daptomycin. METHODS: A 73-year-old man with septic arthritis was infected with VISA. The patient was treated with daptomycin; however, the patient remained infected with VISA, with continuous isolation of VISA from his blood during long-term treatment. Five VISA isolates were characterized by: PFGE; genotyping including staphylococcal cassette chromosome mec (SCCmec), spa and MLST; antimicrobial susceptibility testing; and scanning and transmission electron microscopy. WGS and fatty acid analysis were also performed. RESULTS: The five VISA isolates were from a single clone of ST239/spa3(t037) and, of these, the first three were SCCmecIII positive and daptomycin susceptible, whereas the last two were SCCmecIII negative and daptomycin resistant and exhibited the characteristics of SCVs. The first and last isolates showed 13 remarkable genetic differences in SCCmec and the mprF, cls2, clpX and fabF genes. Of these, mutation of fabF (encoding the fatty acid synthase) seemed to be partially responsible for the slow growth and ultrastructural features, including an abnormal intercellular substance, and for the daptomycin resistance of SCVs. CONCLUSIONS: For the first time, we identified SCVs of VISA in a patient with septic arthritis during long-term treatment with daptomycin. Daptomycin-resistant SCVs of VISA were evolved in a stepwise manner and the mutation of fabF is likely responsible for the physical and ultrastructural characteristics and daptomycin resistance.
OBJECTIVES: Small colony variants (SCVs) of Staphylococcus aureus are associated with persistent and drug-resistant infections. We demonstrated for the first time the emergence of SCVs in a patient with vancomycin-intermediate S. aureus (VISA) infection during long-term treatment with daptomycin. METHODS: A 73-year-old man with septic arthritis was infected with VISA. The patient was treated with daptomycin; however, the patient remained infected with VISA, with continuous isolation of VISA from his blood during long-term treatment. Five VISA isolates were characterized by: PFGE; genotyping including staphylococcal cassette chromosome mec (SCCmec), spa and MLST; antimicrobial susceptibility testing; and scanning and transmission electron microscopy. WGS and fatty acid analysis were also performed. RESULTS: The five VISA isolates were from a single clone of ST239/spa3(t037) and, of these, the first three were SCCmecIII positive and daptomycin susceptible, whereas the last two were SCCmecIII negative and daptomycin resistant and exhibited the characteristics of SCVs. The first and last isolates showed 13 remarkable genetic differences in SCCmec and the mprF, cls2, clpX and fabF genes. Of these, mutation of fabF (encoding the fatty acid synthase) seemed to be partially responsible for the slow growth and ultrastructural features, including an abnormal intercellular substance, and for the daptomycin resistance of SCVs. CONCLUSIONS: For the first time, we identified SCVs of VISA in a patient with septic arthritis during long-term treatment with daptomycin. Daptomycin-resistant SCVs of VISA were evolved in a stepwise manner and the mutation of fabF is likely responsible for the physical and ultrastructural characteristics and daptomycin resistance.
Authors: Irina N Protasova; Tsai-Wen Wan; Natalya V Bakhareva; Wei-Chun Hung; Wataru Higuchi; Yasuhisa Iwao; Tatyana A Yelistratova; Natalya A Ilyenkova; Yelena S Sokolovskaya; Galina P Martynova; Ivan V Reva; Galina V Reva; Sergey V Sidorenko; Lee-Jene Teng; Olga V Peryanova; Alla B Salmina; Tatsuo Yamamoto Journal: Microbiol Immunol Date: 2017-09 Impact factor: 1.955
Authors: Nina Schleimer; Ursula Kaspar; Mike Drescher; Jochen Seggewiß; Christof von Eiff; Richard A Proctor; Georg Peters; André Kriegeskorte; Karsten Becker Journal: Front Microbiol Date: 2018-08-14 Impact factor: 5.640