Selection of quinolone resistance in Streptococcus pneumoniae exposed in vitro to subinhibitory drug concentrations

Abstract

Exposure of Streptococcus pneumoniae to subinhibitory MICs of ciprofloxacin, a substrate for efflux pumps, results in patA/B-mediated efflux whatever the initial level of expression of pmrA of the strain. Quinolones that are poorly (levofloxacin) or not affected (moxifloxacin, garenoxacin) in their activity by efflux transporters preferentially select for target site mutants.

Overexpression of patA and patB , Which Encode ABC Transporters, Is Associated with Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae

“…This result is consistent with those of previous reports suggesting that levofloxacin, as a hydrophobic fluoroquinolone, is poorly transported by the PatA and PatB transporters compared to their transport of the hydrophilic fluoroquinolones ciprofloxacin and norfloxacin (4).…”

Overexpression of an ABC transporter and mutations of GyrA, GyrB, and ParC in contributing to high-level ciprofloxacin resistance in Streptococcus suis type 2

“…Only one strain had a single mutation in GyrB without mutations in GyrA, ParC, or ParE. The resistance mutations in GyrA and ParC in our strains occurred at the expected hot spots (GyrA-S81Y; ParC-S79Y), which are generally similar to those reported by Escudero et al (13) and those in other Gram-positive bacteria, such as S. aureus, S. pneumoniae, S. pyogenes, and E. faecium (18,(24)(25)(26)(27). It has already been demonstrated that QRDR alterations in GyrB and ParE are associated with fl uoroquinolone resistance in Gram-positive bacteria such as S. aureus, S. pneumoniae, and E. faecium (25,27,28), but this has not been reported in S. suis.…”

“…The mRNA expression of the related efflux genes satAB and smrA as well as the identified ABC transporter gene selected by the proteome, were detected by real-time RT-PCR, as previously described (18). 16S rRNA was used as a housekeeping gene to standardize the levels of the transcripts.…”

Fluoroquinolone Efflux in Streptococcus suis Is Mediated by SatAB and Not by SmrA

“…Since its first description (12), PmrA has generally failed to be further related to FQ resistance in either wild-type strains or laboratory mutants (1,5,28,35). Its role in fluoroquinolone resistance therefore remains unclear and is now questioned.…”