Abstract |
Vancomycin is frequently added to standard therapy for pneumococcal meningitis. Although vancomycin-resistant Streptococcus pneumoniae strains have not been isolated, reports on the emergence of vancomycin-tolerant pneumococci are a cause of concern. To date, the molecular basis of vancomycin tolerance in S. pneumoniae is essentially unknown. We examined two vancomycin-tolerant clinical isolates, i.e. a purported autolysin negative (LytA(-)), serotype 23F isolate (strain S3) and the serotype 14 strain 'Tupelo', which is considered a paradigm of vancomycin tolerance. S3 was characterized here as carrying a frameshift mutation in the lytA gene encoding the main pneumococcal autolysin. The vancomycin tolerance of strain S3 was abolished by transformation to the autolysin-proficient phenotype. The original Tupelo strain was discovered to be a mixture: a strain showing a vancomycin-tolerant phenotype (Tupelo_VT) and a vancomycin-nontolerant strain (Tupelo_VNT). The two strains differed only in terms of a single mutation in the ciaH gene present in the VT strain. Most interestingly, although the vancomycin tolerance of Tupelo_VT could be overcome by increasing the LytA dosage upon transformation by a multicopy plasmid or by externally adding the autolysin, we show that vancomycin tolerance in S. pneumoniae requires the simultaneous presence of a mutated CiaH histidine kinase and capsular polysaccharide.
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Authors | Miriam Moscoso, Mirian Domenech, Ernesto García |
Journal | Molecular microbiology
(Mol Microbiol)
Vol. 77
Issue 4
Pg. 1052-64
(Aug 2010)
ISSN: 1365-2958 [Electronic] England |
PMID | 20598082
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2010 Blackwell Publishing Ltd. |
Chemical References |
- Anti-Bacterial Agents
- DNA, Bacterial
- Polysaccharides, Bacterial
- Vancomycin
- Protein Kinases
- Histidine Kinase
- N-Acetylmuramoyl-L-alanine Amidase
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Topics |
- Anti-Bacterial Agents
(pharmacology)
- DNA, Bacterial
(chemistry, genetics)
- Drug Tolerance
- Frameshift Mutation
- Gene Dosage
- Genetic Complementation Test
- Histidine Kinase
- Molecular Sequence Data
- N-Acetylmuramoyl-L-alanine Amidase
(genetics, metabolism)
- Polysaccharides, Bacterial
(metabolism)
- Protein Kinases
(genetics, metabolism)
- Sequence Analysis, DNA
- Streptococcal Infections
(microbiology)
- Streptococcus pneumoniae
(drug effects, enzymology, genetics, isolation & purification)
- Vancomycin
(pharmacology)
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