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Published on: May 2, 2018
Role of parC Mutations at Position 84 on High-Level Delafloxacin Resistance in Methicillin-Resistant Staphylococcus
Silvia Bolaños1, Cesar Acebes1, Óscar Martínez-Expósito1
1Servicio de Microbiología, Hospital Universitario Central de Asturias (HUCA), Avenida de Roma s/n, 33011 Oviedo, Spain.
Abstract:
High-level delafloxacin-resistant (H-L DLX-R) Staphylococcus aureus isolates (minimum inhibitory concentration ≥1 mg/L) associated with mutations affecting position 84 of ParC have emerged. We aimed to elucidate the role of these mutations as a mechanism of H-L DLX resistance in methicillin-resistant S. aureus (MRSA) isolates recovered from blood cultures. Susceptibility to DLX was determined in 75 MRSA isolates by E-test, and an rt-PCR was developed to detect mutations affecting position 84 of ParC to screen a further 185 MRSA isolates. The genomes of 48 isolates, including all DLX-R isolates or with alterations at position 84, and also a subset of DLX-susceptible isolates were analyzed. Among the 75 isolates studied, 77.34% were DLX-susceptible and only 4 H-L DLX-R isolates were found. Seven (3.8%) isolates with alterations at position 84 of ParC were detected by rt-PCR. Genomic analysis showed that 89.9% (8/9) of isolates with the substitution E84K/G in ParC, together with other mutations in gyrA and parC, were H-L DLX-R. However, the E84K substitution in ParC alone or with other alterations was found in two isolates without H-L DLX-R. Alterations at position 84 of ParC are rare but play a key role in H-L DLX resistance in MRSA but only when other alterations in GyrA are present.
Insights
High-level delafloxacin resistance in MRSA is rare but linked to ParC mutations. These mutations are key for resistance only when combined with GyrA alterations.
Area of Science:
- Microbiology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Emergence of high-level delafloxacin resistance (H-L DLX-R) in *Staphylococcus aureus* is a growing concern.
- Mutations in the ParC protein at position 84 have been associated with delafloxacin resistance.
Purpose of the Study:
- To investigate the role of mutations at position 84 of ParC in conferring H-L DLX resistance in methicillin-resistant *S. aureus* (MRSA).
Main Methods:
- Susceptibility testing (E-test) on 75 MRSA isolates.
- Real-time PCR (rt-PCR) to detect ParC position 84 mutations in 185 MRSA isolates.
- Whole-genome sequencing of 48 selected MRSA isolates.
Main Results:
- Only 4 H-L DLX-R isolates were identified among 75 tested.
- rt-PCR detected ParC alterations at position 84 in 3.8% of isolates.
- Genomic analysis revealed that 89.9% of isolates with ParC E84K/G substitutions and additional *gyrA*/*parC* mutations exhibited H-L DLX-R.
- ParC E84K substitution alone or with other alterations did not consistently confer H-L DLX-R.
Conclusions:
- Alterations at position 84 of ParC are infrequent in MRSA.
- These mutations are critical for H-L DLX resistance in MRSA, but their contribution is dependent on the presence of co-occurring mutations in *gyrA*.
