Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Domenech, Arnau; Tirado-Vélez, Jose Manuel; Fenoll, Asunción; Ardanuy, Carmen; Yuste, José; Liñares, Josefina; Campa, Adela G. de la

doi:10.1128/aac.02669-13

Cited by 22 publications

(17 citation statements)

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“…Of note, increasing antibiotic resistance has been recently detected both in serotype 35B [ 42 , 43 ] and serotype 11A S . pneumoniae isolates [ 44 ]. However, since pneumococcal vaccines have been dessigned for the active prevention of IPD and pneumococci of serotypes 11A and 35B only seldom cause IPD [ 45 – 47 ], it is questionable whether these serotypes should be included in future higher-valency PCVs.…”

Section: Discussionmentioning

confidence: 99%

Emerging, Non-PCV13 Serotypes 11A and 35B of Streptococcus pneumoniae Show High Potential for Biofilm Formation In Vitro

et al. 2015

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BackgroundSince the use of pneumococcal conjugate vaccines PCV7 and PCV13 in children became widespread, invasive pneumococcal disease (IPD) has dramatically decreased. Nevertheless, there has been a rise in incidence of Streptococcus pneumoniae non-vaccine serotypes (NVT) colonising the human nasopharynx. Nasopharyngeal colonisation, an essential step in the development of S. pneumoniae-induced IPD, is associated with biofilm formation. Although the capsule is the main pneumococcal virulence factor, the formation of pneumococcal biofilms might, in fact, be limited by the presence of capsular polysaccharide (CPS).Methodology/Principal FindingsWe used clinical isolates of 16 emerging, non-PCV13 serotypes as well as isogenic transformants of the same serotypes. The biofilm formation capacity of isogenic transformants expressing CPSs from NVT was evaluated in vitro to ascertain whether this trait can be used to predict the emergence of NVT. Fourteen out of 16 NVT analysed were not good biofilm formers, presumably because of the presence of CPS. In contrast, serotypes 11A and 35B formed ≥45% of the biofilm produced by the non-encapsulated M11 strain.Conclusions/SignificanceThis study suggest that emerging, NVT serotypes 11A and 35B deserve a close surveillance.

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Section: Discussionmentioning

confidence: 99%

Emerging, Non-PCV13 Serotypes 11A and 35B of Streptococcus pneumoniae Show High Potential for Biofilm Formation In Vitro

et al. 2015

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“…Nowadays, the fluoroquinolones (FQs) levofloxacin (LVX) and moxifloxacin (MXF) are indicated for the treatment of adult patients with pneumonia (Mandell et al, 2007 ). Although FQ-resistance in S. pneumoniae is low (<3%) in Europe (Riedel et al, 2007 ; Domenech et al, 2014 ), it is higher in Asia (10.5%, Ip et al, 2007 ), and in Canada (7.3%, Adam et al, 2009 ). However, an increase in resistance may occur if the use of these drugs increases (Chen et al, 1999 ).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of the PatAB Transporter Confers Fluoroquinolone Resistance to Streptococcus pseudopneumoniae

et al. 2017

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We characterized the mechanism of fluoroquinolone-resistance in two isolates of Streptococcus pseudopneumoniae having fluoroquinolone-efflux as unique mechanism of resistance. Whole genome sequencing and genetic transformation experiments were performed together with phenotypic determinations of the efflux mechanism. The PatAB pump was identified as responsible for efflux of ciprofloxacin (MIC of 4 μg/ml), ethidium bromide (MICs of 8–16 μg/ml) and acriflavine (MICs of 4–8 μg/ml) in both isolates. These MICs were at least 8-fold lower in the presence of the efflux inhibitor reserpine. Complete genome sequencing indicated that the sequence located between the promoter of the patAB operon and the initiation codon of patA, which putatively forms an RNA stem-loop structure, may be responsible for the efflux phenotype. RT-qPCR determinations performed on RNAs of cultures treated or not treated with subinhibitory ciprofloxacin concentrations were performed. While no significant changes were observed in wild-type Streptococcus pneumoniae R6 strain, increases in transcription were detected in the ciprofloxacin-efflux transformants obtained with DNA from efflux-positive isolates, in the ranges of 1.4 to 3.4-fold (patA) and 2.1 to 2.9-fold (patB). Ciprofloxacin-induction was related with a lower predicted free energy for the stem-loop structure in the RNA of S. pseudopneumoniae isolates (−13.81 and −8.58) than for R6 (−15.32 kcal/mol), which may ease transcription. The presence of these regulatory variations in commensal S. pseudopneumoniae isolates, and the possibility of its transfer to Streptococcus pneumoniae by genetic transformation, could increase fluoroquinolone resistance in this important pathogen.

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“…The fluoroquinolones (FQs) levofloxacin (LVX) and moxifloxacin (MOX) are currently used for the treatment of adult patients with pneumonia. FQ resistance in S. pneumoniae is minimally prevalent (Ͻ3%) in Europe (3,4), although higher rates have been detected in Asia (10.5%) (5) and in Canada (7.3%) (6). This low prevalence allows successful treatment of pneumococcal pneumonia with FQs.…”

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Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae

Ferrándiz

Martín-Galiano

Arnanz

et al. 2016

Antimicrob Agents Chemother

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bWe studied the transcriptomic response of Streptococcus pneumoniae to the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10؋ the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H 2 O 2 ), an increase in pyruvate would augment intracellular H 2 O 2 . Here, we confirm a 21-fold increase in the production of H 2 O 2 and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response of S. pneumoniae to moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction.

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Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Cited by 22 publications

References 41 publications

Emerging, Non-PCV13 Serotypes 11A and 35B of Streptococcus pneumoniae Show High Potential for Biofilm Formation In Vitro

Emerging, Non-PCV13 Serotypes 11A and 35B of Streptococcus pneumoniae Show High Potential for Biofilm Formation In Vitro

Upregulation of the PatAB Transporter Confers Fluoroquinolone Resistance to Streptococcus pseudopneumoniae

Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae

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