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Antimicrobial Agents and Chemotherapy, July 2001, p. 2075-2081, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2075-2081.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

All Detectable High-Molecular-Mass Penicillin-Binding Proteins Are Modified in a High-Level beta -Lactam-Resistant Clinical Isolate of Streptococcus mitis

Ana Amoroso,1 Diego Demares,1 Marta Mollerach,1 Gabriel Gutkind,1,* and Jacques Coyette2

Laboratorio de resistencia microbiana, Cátedra de Microbiología. Departamento de Microbiología, Inmunología y Biotecnología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina,1 and Centre d'ingenierie des Protéines, Institut de Chimie, Université de Liège, Sart Tilman, Liege, Belgium2

Received 9 October 2000/Returned for modification 29 January 2001/Accepted 6 April 2001

All detectable high-molecular-mass penicillin-binding proteins (HMM PBPs) are altered in a clinical isolate of Streptococcus mitis for which the beta -lactam MICs are increased from those previously reported in our region (cefotaxime MIC, 64 µg/ml). These proteins were hardly detected at concentrations that saturate all PBPs in clinical isolates and showed, after densitometric analysis, 50-fold-lower radiotracer binding. Resistance was related to mosaic structure in all HMM PBP-coding genes, where critical region replacement was complemented not only by substitutions already reported for the closely related Streptococcus pneumoniae but also by other specific replacements that are presumably close to the active-site serine. Mosaic structure was also presumed in a pbp1a-sensitive strain used for comparison, confirming that these structures do not unambiguously imply, by themselves, detectable critical changes in the kinetic properties of these proteins.


* Corresponding author. Mailing address: Laboratorio de resistencia microbiana, Cátedra de Microbiología. Departamento de Microbiología, Inmunología y Biotecnología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956 (1113) Buenos Aires, Argentina. Phone: 54 11 4964 8285. Fax: 54 11 4962. 5341. E-mail: ggutkind{at}huemul.ffyb.uba.ar.


Antimicrobial Agents and Chemotherapy, July 2001, p. 2075-2081, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2075-2081.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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