Heteroresistance to Fosfomycin Is Predominant in Streptococcus pneumoniae and Depends on the murA1 Gene

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

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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)


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 and Hathaway, Lucy Jane


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




American Society for Microbiology




Factscience Import

Date Deposited:

04 Oct 2013 14:40

Last Modified:

10 Mar 2014 11:22

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Web of Science ID:



https://boris.unibe.ch/id/eprint/16229 (FactScience: 223824)

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