scholarly journals Examination of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Mutants with Low-Level Fluoroquinolone Resistance

1998 ◽  
Vol 42 (12) ◽  
pp. 3317-3319 ◽  
Author(s):  
Mark C. Sulavik ◽  
Neil L. Barg
Keyword(s):  
Staphylococcus Aureus ◽  
Ethidium Bromide ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Methicillin Resistant ◽  
Low Level ◽  
High Level

ABSTRACT For Staphylococcus aureus, stepwise mutations result in high-level quinolone resistance. Methicillin-resistant and -susceptible quinolone-resistant, first-step mutants generated in vitro were obtained and found to be no different than those recovered from murine abscesses. Approximately 10% of all first-step mutants were resistant to ethidium bromide, and selected strains had mutations that mapped toflqB. NorA-mediated resistance among first-step mutants may be more prevalent than previously reported.

scholarly journals Heterogeneity of Genetic Pathways toward Daptomycin Nonsusceptibility in Staphylococcus aureus Determined by Adjunctive Antibiotics

2015 ◽  
Vol 59 (5) ◽  
pp. 2799-2806 ◽  
Author(s):  
Andrew D. Berti ◽  
Sarah L. Baines ◽  
Benjamin P. Howden ◽  
George Sakoulas ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Efficacy ◽  
Combined Exposure ◽  
Genetic Pathways ◽  
Methicillin Resistant ◽  
Content Type ◽  
Low Level ◽  
Whole Genomes ◽  
High Level

ABSTRACTDaptomycin is increasingly used in combination with other antibiotics to enhance antimicrobial efficacy and/or to mitigate the emergence of daptomycin nonsusceptibility (DNS). This study used a clinical methicillin-resistantStaphylococcus aureus(MRSA) strain in which DNS emerged upon therapy to examine the influence of antibiotic combinations on the development of mutations in specific genes (mprF,rpoBC,dltA,cls2, andyycFG) previously associated with DNS. Whole genomes of bacteria obtained following 28 days ofin vitroexposure to daptomycin with or without adjunctive clarithromycin, linezolid, oxacillin, or trimethoprim-sulfamethoxazole were sequenced, and the sequences were compared to that of the progenitor isolate. The addition of oxacillin to medium containing daptomycin prevented the emergence ofmprFmutation but did not preventrpoBCmutation (P< 0.01). These isolates maintained susceptibility to daptomycin during the combined exposure (median MIC, 1 mg/liter). Daptomycin plus clarithromycin or linezolid resulted in low-level (1.5 to 8 mg/liter) and high-level (12 to 96 mg/liter) DNS, respectively, and did not preventmprFmutation. However, these same combinations preventedrpoBCmutation. Daptomycin alone or combined with linezolid or trimethoprim-sulfamethoxazole resulted in high-level DNS and mutations inmprFplusrpoBC,cls2, andyycFG. Combining daptomycin with different antimicrobials alters the mutational space available for DNS development, thereby favoring the development of predictable collateral susceptibilities.

scholarly journals High-level fluoroquinolone resistance in Streptococcus pneumoniae requires mutations in parC and gyrA.

1996 ◽  
Vol 40 (12) ◽  
pp. 2760-2764 ◽  
Author(s):  
C Janoir ◽  
V Zeller ◽  
M D Kitzis ◽  
N J Moreau ◽  
L Gutmann
Keyword(s):  
Streptococcus Pneumoniae ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Clinical Samples ◽  
Low Frequencies ◽  
Low Level ◽  
Resistant Strains ◽  
High Level ◽  
Level Resistance

The mechanism of high-level fluoroquinolone resistance was studied in strains of Streptococcus pneumoniae, either selected in vitro or isolated from clinical samples. By using DNA from these high-level-resistant strains, low-level-resistant transformants (MIC of pefloxacin, > or = 32 micrograms/ml; MIC of ciprofloxacin, 4 micrograms/ml; MIC of sparfloxacin, 0.50 micrograms/ml) were obtained at high frequencies (ca.10(-2)), while high-level-resistant transformants (MIC of pefloxacin, > or = 64 micrograms/ml; MIC of ciprofloxacin, 16 to 64 micrograms/ml; MIC of sparfloxacin, > or = 8 micrograms/ml) were obtained only at low frequencies (ca.10(-4)). This suggested that mutations in at least two unlinked genes were necessary to obtain high-level resistance. Low-level resistance was associated with ParC mutations (change from Ser to Tyr at position 79 [Ser79Tyr], Ser79Phe, or Asp83Gly). ParC mutations were associated, in high-level-resistant strains and transformants, with alterations in the quinolone resistance-determining region of GyrA (Ser84Tyr, Ser84Phe, and/or Glu88Lys). Low-level resistance was shown to be necessary for expression of the gyrA mutations. No mutation in the region corresponding to the quinolone resistance-determining region of GyrB and no alteration of drug accumulation were found.

scholarly journals Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro.

1996 ◽  
Vol 40 (11) ◽  
pp. 2505-2510 ◽  
Author(s):  
J Tankovic ◽  
B Perichon ◽  
J Duval ◽  
P Courvalin
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gene Amplification ◽  
Low Frequency ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Primary Target ◽  
Total Dna

We have analyzed by gene amplification and sequencing mutations in the quinolone resistance-determining regions of the gyrA, gyrB, and parC genes of fluoroquinolone-resistant Streptococcus pneumoniae mutants obtained during therapy or in vitro. Mutations leading to substitutions in ParC were detected in the two mutants obtained in vivo, BM4203-R (substitution of a histidine for an aspartate at position 84 [Asp-84-->His]; Staphylococcus aureus coordinates) and BM4204-R (Ser-80-->Phe), and in two mutants obtained in vitro (Ser-80-->Tyr). An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84-->Phe change. We could not detect any mutation in the three remaining mutants obtained in vitro. Total DNA from BM4203-R, BM4204-R, and BM4205-R3 was used to transform S. pneumoniae CP1000 by selection on fluoroquinolones. For the parC mutants, transformants with phenotypes indistinguishable from those of the donors were obtained at frequencies (5 x 10(-3) to 8 x 10(-3)) compatible with monogenic transformation. By contrast, transformants were obtained at a low frequency (4 x 10(-5)), compatible with the transformation of two independent genes, for the gyrA mutant. Resistant transformants of CP1000 were also obtained with an amplified fragment of parC from BM4203-R and BM4204-R but not with a gyrA fragment from BM4205-R3. All transformants had mutations identical to those in the donors. These data strongly suggest that ParC is the primary target for fluoroquinolones in S. pneumoniae and that BM4205-R3 is resistant to higher levels of the drugs following the acquisition of two mutations, including one in gyrA.

scholarly journals Prevalence and molecular characterization of methicillin-resistant Staphylococcus aureus with mupirocin, fusidic acid and/or retapamulin resistance

2020 ◽  
Author(s):  
Wenjing Chen ◽  
Chunyan He ◽  
Han Yang ◽  
Wen Shu ◽  
Zelin Cui ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Resistance Mechanisms ◽  
Antibiotics Resistance ◽  
Genetic Characteristics ◽  
Methicillin Resistant ◽  
Low Level ◽  
High Level ◽  
Level Resistance

Abstract Data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. In this study we examined these three antibiotics resistance pheno and geno-typically in 1206 MRSA clinical isolates. Phenotypic MUP, FA and RET resistance was determined by MICs, and genotypically by PCR and DNA sequencing examining genes mupA / B , fusB - D , cfr and vgaA / Av , and mutations in ileS , fusA / E , rplC , and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by PFGE and MLST. Overall MRSA MUP, FA and RET resistance was low (5.1%, 1.0% and 0.3%, respectively). The mupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS, and 2 of them additionally had the reported V588F mutation impacting the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I, were the primary FA resistance mechanisms among high-level resistance isolates, most of which contained fusC ; however, all low-level resistance strains carried fusB . No resistance mechanisms detected were found among RET resistance isolates. Genetic analysis demonstrated clone spread for MUP resistance isolates. In conclusion, MUP, FA and RET exhibited highly activity against MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance, and further investigation is needed to uncover the RET resistance mechanisms. Moreover, the surveillance to MUP in MRSA should be strengthened to prevent resistance increase due to the expansion of clones.

scholarly journals Fluoroquinolone Resistance Mutations in the parC,parE, and gyrA Genes of Clinical Isolates of Viridans Group Streptococci

1998 ◽  
Vol 42 (11) ◽  
pp. 2792-2798 ◽  
Author(s):  
Irene González ◽  
Marios Georgiou ◽  
Fernando Alcaide ◽  
Delia Balas ◽  
Josefina Liñares ◽  
...  
Keyword(s):  
Nucleotide Sequences ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Resistance Mutations ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
Low Level ◽  
Equivalent Residue ◽  
High Level ◽  
Viridans Group Streptococci

ABSTRACT The nucleotide sequences of the quinolone resistance-determining regions (QRDRs) of the parC and gyrA genes from seven ciprofloxacin-resistant (Cpr) isolates of viridans group streptococci (two high-level Cpr Streptococcus oralis and five low-level Cpr Streptococcus mitis isolates) were determined and compared with those obtained from susceptible isolates. The nucleotide sequences of the QRDRs of the parE and gyrBgenes from the five low-level Cpr S. mitisisolates and from the NCTC 12261 type strain were also analyzed. Four of these low-level Cpr isolates had changes affecting the subunits of DNA topoisomerase IV: three in Ser-79 (to Phe or Ile) of ParC and one in ParE at a position not previously described to be involved in quinolone resistance (Pro-424). One isolate did not show any mutation. The two high-level Cpr S. oralisisolates showed mutations affecting equivalent residue positions of ParC and GyrA, namely, Ser-79 to Phe and Ser-81 to Phe or Tyr, respectively. The parC mutations were able to transformStreptococcus pneumoniae to ciprofloxacin resistance, while the gyrA mutations transformed S. pneumoniaeonly when mutations in parC were present. These results suggest that DNA topoisomerase IV is a primary target of ciprofloxacin in viridans group streptococci, DNA gyrase being a secondary target.

scholarly journals Ceftobiprole- and Ceftaroline-Resistant Methicillin-Resistant Staphylococcus aureus

2015 ◽  
Vol 59 (5) ◽  
pp. 2960-2963 ◽  
Author(s):  
Liana C. Chan ◽  
Li Basuino ◽  
Binh Diep ◽  
Stephanie Hamilton ◽  
Som S. Chatterjee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Low Level ◽  
Mrsa Strains ◽  
High Level ◽  
Level Resistance

ABSTRACTThe role ofmecAmutations in conferring resistance to ceftobiprole and ceftaroline, cephalosporins with anti-methicillin-resistantStaphylococcus aureus(MRSA) activity, was determined with MRSA strains COL and SF8300. The SF8300 ceftaroline-passaged mutant carried a singlemecAmutation, E447K (E-to-K change at position 447), and expressed low-level resistance. This mutation in COL conferred high-level resistance to ceftobiprole but only low-level resistance to ceftaroline. The COL ceftaroline-passaged mutant, which expressed high-level resistance to ceftobiprole and ceftaroline, had mutations inpbp2,pbp4, andgdpPbut notmecA.

scholarly journals Alterations in the Quinolone Resistance-Determining Regions and Fluoroquinolone Resistance in Clinical Isolates and Laboratory-Derived Mutants of Mycoplasma bovis: Not All Genotypes May Be Equal

2015 ◽  
Vol 82 (4) ◽  
pp. 1060-1068 ◽  
Author(s):  
Dima Khalil ◽  
Claire A. M. Becker ◽  
Florence Tardy
Keyword(s):  
Point Mutations ◽  
Slight Modification ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Mycoplasma Bovis ◽  
Content Type ◽  
High Level ◽  
Sequence Types

ABSTRACTMycoplasma bovisis considered a major contributor to respiratory diseases in young cattle. ResistantM. bovisisolates have increasingly been reported worldwide due to extensive use of antimicrobials to treat bovine pneumonia. The frequency of isolates resistant to fluoroquinolones varies considerably from one country to another. The MICs of isolates collected in France have only increased from “very low” to “low.” The present study was conducted to investigate whether alterations in the quinolone resistance-determining regions (QRDRs) could account for this slight modification in susceptibility. No correlation between QRDR alterations and increased MICs was evidenced in clinical isolates. In addition, all clinical isolates were subtyped, and the tendencies of the different sequence types to develop resistance through mutations in QRDRs under selective pressurein vitrowere examined.In vitro, 3 hot spots for mutations in QRDRs (position 83 in GyrA and positions 80 and 84 in ParC) were associated with a high level of resistance when cumulated. We showed that the point mutations in the QRDRs observedin vitrowere different (in location and selection rapidity) between the different subtypes. Ourin vitroobservations were corroborated by the recent detection of a clinical isolate highly resistant to fluoroquinolones (MIC ≥ 16 μg/ml) and belonging to the subtype which easily accumulates QRDR alterationsin vitro. The current increased prevalence of this subtype in clinical isolates highlights the urgent need to control fluoroquinolone usage in veterinary medicine.

scholarly journals Evolution of Ciprofloxacin-Resistant Staphylococcus aureus in In Vitro Pharmacokinetic Environments

2004 ◽  
Vol 48 (12) ◽  
pp. 4733-4744 ◽  
Author(s):  
Jeffrey J. Campion ◽  
Patrick J. McNamara ◽  
Martin E. Evans
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Agents ◽  
Fluoroquinolone Resistance ◽  
Resistance Mutations ◽  
Low Level ◽  
Mutant Prevention Concentration ◽  
Evolution Of Resistance ◽  
Ciprofloxacin Resistance ◽  
State Concentration

ABSTRACT The development of novel antibacterial agents is decreasing despite increasing resistance to presently available agents among common pathogens. Insights into relationships between pharmacodynamics and resistance may provide ways to optimize the use of existing agents. The evolution of resistance was examined in two ciprofloxacin-susceptible Staphylococcus aureus strains exposed to in vitro-simulated clinical and experimental ciprofloxacin pharmacokinetic profiles for 96 h. As the average steady-state concentration (C avg ss) increased, the rate of killing approached a maximum, and the rate of regrowth decreased. The enrichment of subpopulations with mutations in grlA and low-level ciprofloxacin resistance also varied depending on the pharmacokinetic environment. A regimen producing values for C avg ss slightly above the MIC selected resistant variants with grlA mutations that did not evolve to higher levels of resistance. Clinical regimens which provided values for C avg ss intermediate to the MIC and mutant prevention concentration (MPC) resulted in the emergence of subpopulations with gyrA mutations and higher levels of resistance. A regimen producing values for C avg ss close to the MPC selected grlA mutants, but the appearance of subpopulations with higher levels of resistance was diminished. A regimen designed to maintain ciprofloxacin concentrations entirely above the MPC appeared to eradicate low-level resistant variants in the inoculum and prevent the emergence of higher levels of resistance. There was no relationship between the time that ciprofloxacin concentrations remained between the MIC and the MPC and the degree of resistance or the presence or type of ciprofloxacin-resistance mutations that appeared in grlA or gyrA. Regimens designed to eradicate low-level resistant variants in S. aureus populations may prevent the emergence of higher levels of fluoroquinolone resistance.

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