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

Authors

  • Manuel Sánchez Centro de Investigación Básica, NPDD–Merck ResearchLaboratories, Merck Sharp & Dohme de España S.A., Madrid, Spain
  • María Francisca Vicente Centro de Investigación Básica, NPDD–Merck Research Laboratories, Merck Sharp & Dohme de España S.A., Madrid, Spain
  • Emilia Cercenado Servicio de Microbiología, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
  • Miguel A. de Pedro Departamento de Biología Molecular, CBM-UAM, Madrid, Spain
  • 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 Departamento de Biología Molecular, CBM-UAM, Madrid, Spain
  • Raquel Morón Centro de Investigación Básica, NPDD–Merck ResearchLaboratories, Merck Sharp & Dohme de España S.A., Madrid, Spain
  • José Berenguer Departamento de Biología Molecular, CBM-UAM, Madrid, Spain

Keywords:

Streptococcus mitis, penicillin-binding proteins, [3H]-benzylpenicillin, intrinsic resistance to antibiotics, PBP1

Abstract

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.

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Published

2010-03-12

Issue

Vol. 4 No. 4 (2001)

Section

Review Articles

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