Association of mprF mutations with cross-resistance to daptomycin and vancomycin in methicillin-resistant Staphylococcus aureus (MRSA)
| Autor: | Feng-Yu Li, Longzhu Cui, Yusuke Sato’o, Teppei Sasahara, Aa Haeruman Azam, Yuancheng Zhang, Kanate Thitiananpakorn, Shinya Watanabe, Tanit Boonsiri, Kotaro Kiga, Yoshifumi Aiba, Yusuke Taki, Xin-Ee Tan |
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| Rok vydání: | 2020 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine Genotype 030106 microbiology Mutant lcsh:Medicine Microbial Sensitivity Tests Biology medicine.disease_cause Microbiology 03 medical and health sciences Bacterial Proteins Daptomycin Cell Wall Vancomycin Gene expression medicine Humans lcsh:Science Cross-resistance Mutation Multidisciplinary Gene Expression Profiling lcsh:R Gene Expression Regulation Bacterial Staphylococcal Infections Aminoacyltransferases Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents Phenotype 030104 developmental biology Staphylococcus aureus lcsh:Q Follow-Up Studies medicine.drug |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) |
| ISSN: | 2045-2322 |
| Popis: | We first reported a phenomenon of cross-resistance to vancomycin (VCM) and daptomycin (DAP) in methicillin-resistant Staphylococcus aureus (MRSA) in 2006, but mechanisms underlying the cross-resistance remain incompletely understood. Here, we present a follow-up study aimed to investigate genetic determinants associated with the cross-resistance. Using 12 sets of paired DAP susceptible (DAPS) and DAP non-susceptible (DAPR) MRSA isolates from 12 patients who had DAP therapy, we (i) assessed susceptibility to DAP and VCM, (ii) compared whole-genome sequences, (iii) identified mutations associated with cross-resistance to DAP and VCM, and (iv) investigated the impact of altered gene expression and metabolic pathway relevant to the cross-resistance. We found that all 12 DAPR strains exhibiting cross-resistance to DAP and VCM carried mutations in mprF, while one DAPR strain with reduced susceptibility to only DAP carried a lacF mutation. On the other hand, among the 32 vancomycin-intermediate S. aureus (VISA) strains isolated from patients treated with VCM, five out of the 18 strains showing cross-resistance to DAP and VCM carried a mprF mutation, while 14 strains resistant to only VCM had no mprF mutation. Moreover, substitution of mprF in a DAPS strain with mutated mprF resulted in cross-resistance and vice versa. The elevated lysyl-phosphatidylglycerol (L-PG) production, increased positive bacterial surface charges and activated cell wall (CW) synthetic pathways were commonly found in both clinical isolates and laboratory-developed mutants that carry mprF mutations. We conclude that mprF mutation is responsible for the cross-resistance of MRSA to DAP and VCM, and treatment with DAP is more likely to select for mprF-mediated cross-resistance than is with VCM. |
| Databáze: | OpenAIRE |
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