Engel, Hansjürg; Gutiérrez-Fernández, Javier; Flückiger, Christine; Martínez-Ripoll, Martín; Mühlemann, Kathrin; Hermoso, Juan A; Hilty, Markus; Hathaway, Lucy Jane (2013). Heteroresistance to Fosfomycin Is Predominant in Streptococcus pneumoniae and Depends on the murA1 Gene. Antimicrobial agents and chemotherapy, 57(6), pp. 2801-8. Washington, D.C.: American Society for Microbiology 10.1128/AAC.00223-13
Full text not available from this repository.Fosfomycin targets the first step of peptidoglycan biosynthesis in Streptococcus pneumoniae catalyzed by UDP-N-acetylglucosamine enolpyruvyltransferase (MurA1). We investigated whether heteroresistance to fosfomycin occurs in S. pneumoniae. We found that of 11 strains tested, all but 1 (Hungary(19A)) displayed heteroresistance and that deletion of murA1 abolished heteroresistance. Hungary(19A) differs from the other strains by a single amino acid substitution in MurA1 (Ala364Thr). To test whether this substitution is responsible for the lack of heteroresistance, it was introduced into strain D39. The heteroresistance phenotype of strain D39 was not changed. Furthermore, no relevant structural differences between the MurA1 crystal structures of heteroresistant strain D39 and nonheteroresistant strain Hungary(19A) were found. Our results reveal that heteroresistance to fosfomycin is the predominant phenotype of S. pneumoniae and that MurA1 is required for heteroresistance to fosfomycin but is not the only factor involved. The findings provide a caveat for any future use of fosfomycin in the treatment of pneumococcal infections.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases 04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology |
UniBE Contributor: |
Mühlemann, Kathrin, Hilty, Markus, Hathaway, Lucy Jane |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
0066-4804 |
Publisher: |
American Society for Microbiology |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:40 |
Last Modified: |
05 Dec 2022 14:12 |
Publisher DOI: |
10.1128/AAC.00223-13 |
PubMed ID: |
23571543 |
Web of Science ID: |
000319272100046 |
URI: |
https://boris.unibe.ch/id/eprint/16229 (FactScience: 223824) |
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