Inability of L22 ribosomal protein alteration to increase macrolide MICs in the absence of efflux mechanism in Haemophilus influenzae HMC-S

The Journal of Antimicrobial Chemotherapy
Mihaela PericPeter C Appelbaum

Abstract

Haemophilus influenzae HMC-C with high-level macrolide resistance after multi-step selection by clarithromycin reverted spontaneously and became hypersusceptible to macrolides. Determination of macrolide resistance mechanism(s) in hypersusceptible and hyperresistant strains. The presence of macrolide efflux in the strains was studied by radioactive erythromycin accumulation. Ribosomal mutations were investigated by sequencing. The possible role of acrAB clusters in macrolide resistance was studied by sequencing and expression analysis. The parent strain had no ribosomal alteration, but both high-level resistant and hypersusceptible strains had R88P mutations in ribosomal protein L22. Radioactive macrolide accumulation studies pointed to the presence of macrolide efflux in the high-level resistant and parent strains, but not in the hypersusceptible derivative. Transformation of hypersusceptible strains using total DNA from the parent strain restored the macrolide efflux system in the hypersusceptible strain, which was confirmed by MIC levels and radioactive erythromycin accumulation similar to that of the mutant resistant strain. Analysis of sequence and transcription of acrAB gene clusters showed no significant differences betw...Continue Reading

Citations

Nov 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sean D Moore, Robert T Sauer
May 26, 2006·Antimicrobial Agents and Chemotherapy·Tatiana BogdanovichPeter C Appelbaum
Feb 24, 2006·Antimicrobial Agents and Chemotherapy·Tatiana BogdanovichPeter C Appelbaum
Apr 13, 2007·Clinical Microbiology Reviews·Stephen TristramPeter C Appelbaum
Aug 11, 2012·American Journal of Respiratory and Critical Care Medicine·Go-Eun ChoiWon-Jung Koh
Aug 15, 2009·Drugs·Xian-Zhi Li, Hiroshi Nikaido
Mar 11, 2005·Expert Opinion on Investigational Drugs·Michael N Alekshun
Nov 26, 2005·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·G A PankuchP C Appelbaum
May 26, 2005·The Journal of Antimicrobial Chemotherapy·Keith Poole
Nov 24, 2007·Journal of Medical Microbiology·Toshinobu HoriiHideji Yanagisawa
Feb 1, 2017·The Journal of Antimicrobial Chemotherapy·Clémence MassipChristophe Gilbert
Mar 25, 2021·The Journal of Antimicrobial Chemotherapy·J G E LaumenC Kenyon

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