Diversity among clinical isolates of penicillin-resistant Streptococcus mitis: indication for a PBP1-dependent way to reach high levels of penicillin resistance

• Manuel Sánchez ^[2] ; María Francisca Vicente ^[2] ; Emilia Cercenado ^[1] ; Miguel A. de Pedro ^[3] ; Pilar Gómez; Centro de Investigación Básica, NPDD–Merck ResearchLaboratories, Merck Sharp & Dohme de España S.A., Madrid, Spain; and Departamento de Biología Molecular, CBM-UAM, Madrid, Spain ; Renata Moreno ^[3] ; Raquel Morón ^[2] ; José Berenguer ^[3]
  1. [1] Hospital General Universitario Gregorio Marañón

     Hospital General Universitario Gregorio Marañón

     Madrid, España

     
  2. [2] Centro de Investigación Básica, NPDD–Merck ResearchLaboratories, Merck Sharp & Dohme de España S.A., Madrid, Spain
  3. [3] Departamento de Biología Molecular, CBM-UAM, Madrid, Spain

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• Localización: International microbiology: official journal of the Spanish Society for Microbiology, ISSN 1139-6709, Vol. 4, Nº. 4, 2001, págs. 217-222
• Idioma: inglés
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  • A total of 12 non-epidemiologically related clinical isolates of Streptococcus mitis that showed different levels of resistance to penicillin were studied. Membrane-protein profiles and penicillin-binding protein (PBP) patterns showed a great polymorphism; and patterns of 4—7 PBPs, withsizes that ranged from ~101 kDa to ~40 kDa, were detected in eachstrai n. No association could be found between PBP pattern and resistance level to penicillin among these isolates. Arbitrarily primed PCR confirmed the genetic diversity among this group of streptococci. One of the isolates of intermediate level of resistance to penicillin, which showed a PBP pattern similar to that of the high-resistance strains, was used as a laboratory model to analyse the mechanism underlying high-resistance acquisition by these strains. A 14-fold increase in penicillin resistance was obtained after a single selection step, which resulted in a decrease in penicillin affinity for PBP1. The size of this PBP (92 kDa) and the differences in PBP profiles of the penicillin-resistant clinical isolates suggest the existence in S. mitis of PBP-mediated mechanisms to acquire high-level resistance to penicillin, among which alterations in PBP1 seem to play a main role, in contrast to the PBP2X mediated mechanism described for other streptococci.