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Antimicrobial Agents and Chemotherapy, June 1998, p. 1392-1396, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A New Ketolide, HMR 3004, Active against Streptococci Inducibly Resistant to Erythromycin

Adriana Rosato,1 Hubert Vicarini,1 Alain Bonnefoy,2 Jean-François Chantot,2 and Roland Leclercq1,*

Service de Bactériologie-Virologie, Hôpital Henri Mondor-Université Paris XII, Créteil,1 and Hoechst-Marion-Roussel, Romainville,2 France

Received 8 December 1997/Returned for modification 13 February 1998/Accepted 24 March 1998

HMR 3004 is a new hydrazono ketolide characterized by a 3-keto function instead of the cladinose moiety. The effect of this antimicrobial agent on inducible and constitutive macrolide-lincosamide-streptogramin B (MLSB) resistance was tested in a lacZ reporter system under control of several ermAM-like attenuator variants. For one constitutively resistant Streptococcus agalactiae strain, three inducibly resistant Streptococcus pneumoniae strains, and one inducibly resistant Enterococcus faecalis strain, the attenuators fused with lacZ were cloned into the shuttle plasmid pJIM2246 and the plasmid was introduced into Staphylococcus aureus RN4220. For the wild-type attenuators, HMR 3004 was a very weak inducer, unlike its cladinose counterpart RU 6652 and erythromycin. As expected, for the fusion originating from the constitutively resistant S. agalactiae strain, the level of uninduced beta -galactosidase synthesis was high. For one S. pneumoniae attenuator, mutations in the 3' end of the attenuator that weakened the stem-loop structure that sequesters the ribosome-binding site and start codon for ermAM methylase could explain the high level of uninduced beta -galactosidase produced. For streptococci, the activity of HMR 3004 correlated with the basal level of beta -galactosidase synthesized. The weak inducer activity of HMR 3004 explained its activity against inducibly MLSB-resistant S. pneumoniae but did not correlate with the moderate activity of the antibiotic against inducibly resistant E. faecalis.

* Corresponding author. Present mailing address: CHU de Caen, Service de Microbiologie, Avenue Côte de Nacre, 14033 Caen cedex, France. Phone: (33) 2 31 06 45 72. Fax: (33) 2 31 06 45 73. E-mail: leclercq-r{at}chu-caen.fr.

Antimicrobial Agents and Chemotherapy, June 1998, p. 1392-1396, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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