Alterations in the GyrA and GyrB subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa

Lee, Jeom Kyu; Lee, Yeong Seon; Park, Yong Keun; Kim, Bong Su

doi:10.1016/j.ijantimicag.2004.11.012

Cited by 101 publications

(126 citation statements)

References 29 publications

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“…With respect to target site mutations in fluoroquinoloneresistant P. aeruginosa, we observed mutations consistent with those previously published in all isolates (Higgins et al, 2003;Lee et al, 2005;Mouneimné et al, 1999). Substitution of threonine by isoleucine at position 83 in gyrA was the most frequent mutation in our fluoroquinoloneresistant isolates.…”

Section: Discussionsupporting

confidence: 91%

“…However, we also noted a high frequency of gentamicin resistance among isolates harbouring the exoS, exoT, exoY and exoU genes. This resistance appears to be drug specific rather than class specific, as our strains presented a lower frequency of resistance to amikacin.With respect to target site mutations in fluoroquinoloneresistant P. aeruginosa, we observed mutations consistent with those previously published in all isolates (Higgins et al, 2003;Lee et al, 2005;Mouneimné et al, 1999). Substitution of threonine by isoleucine at position 83 in gyrA was the most frequent mutation in our fluoroquinoloneresistant isolates.…”

supporting

confidence: 91%

“…The target regions were amplified by PCR using the primers and conditions described in Table S1 ( Lee et al, 2005). Purified PCR-amplified DNA was sequenced directly using an automatic sequencer ABI-PRISM 3100 Genetic Analyzer armed with 50 cm capillaries and POP6 polymer (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

“…Resistance to fluoroquinolone has become an increasing problem and now has the highest resistance rates in Latin American countries (Andrade et al, 2006;Sader et al, 2001), and is associated with mutations in the quinolone resistance-determining regions (QRDRs), especially the genes encoding DNA gyrase (gyrA) and topoisomerase IV (parC) (Higgins et al, 2003;Lee et al, 2005;Mouneimné et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…In Brazil this problem is hih5ghly significant and some studies show a very high density of antibiotic use, especially of carbapenems and fluoroquinolones (Moreira et al, 2013;Porto et al, 2013). The resistance of P. aeruginosa to carbapenems is higher than 60 % in some Brazilian hospitals (Baumgart et al, 2010;Sader et al, 2005) and the production of metallo-b-lactamase (MBL) encoded by several genes, including bla SPM-1 , bla VIM and bla IMP , is considered the main mechanism of resistance to these antibiotics (Sader et al, 2005).Resistance to fluoroquinolone has become an increasing problem and now has the highest resistance rates in Latin American countries (Andrade et al, 2006;Sader et al, 2001), and is associated with mutations in the quinolone resistance-determining regions (QRDRs), especially the genes encoding DNA gyrase (gyrA) and topoisomerase IV (parC) (Higgins et al, 2003;Lee et al, 2005;Mouneimné et al, 1999).Recent studies have shown that a large number of genes expressed by P. aeruginosa clinical strains are implicated directly in the pathogenesis of severe infections caused by this micro-organism (Aldred et al, 2014;Bleves et al, 2010; Golovkine et al, 2014). Among these is the type III secretion system (TTSS), which delivers effector toxins (ExoS, ExoT, ExoY and ExoU) directly into host cells (Galán & Collmer, 1999;Hauser, 2009).…”

mentioning

confidence: 99%

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Molecular epidemiological survey of the quinolone- and carbapenem-resistant genotype and its association with the type III secretion system in Pseudomonas aeruginosa

Ferreira

Dantas

Faria

et al. 2015

Journal of Medical Microbiology

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This study evaluated the predictors of mortality and the impact of inappropriate therapy on the outcomes of patients with bacteraemia and ventilator-associated pneumonia (VAP). Additionally, we evaluated the correlation of the type III secretion system (TTSS) effector genotype with resistance to carbapenems and fluoroquinolones, mutations in the quinolone resistancedetermining regions (QRDRs), metallo-b-lactamase and virulence factors. A retrospective cohort was conducted at a tertiary hospital in patients with multidrug-resistant (MDR) P. aeruginosa bacteraemia (157 patients) and VAP (60 patients). The genes for bla IMP , bla VIM , bla SIM , bla GIM and bla SPM and virulence genes (exoT, exoS, exoY, exoU, lasB, algD and toxA) were detected; sequencing was conducted for QRDR genes on fluoroquinolone-resistant strains. The multivariate analyses showed that the predictors independently associated with death in patients with bacteraemia were cancer and inappropriate therapy. Carbapenem resistance was more frequent among strains causing VAP (53.3 %), and in blood we observed the bla SPM genotype (66.6 %) and bla VIM genotype (33.3 %). The exoS gene was found in all isolates, whilst the frequency was low for exoU (9.4 %). Substitution of threonine to isoleucine at position 83 in gyrA was the most frequent mutation among fluoroquinolone-resistant strains. Our study showed a mutation at position 91 in the parC gene (Glu91Lys) associated with a mutation in gyrA (Thre83Ile) in a strain of extensively drug-resistant P. aeruginosa, with the exoT + exoS + exoU + genotype, that has not yet been described in Brazil to the best of our knowledge. This comprehensive analysis of resistance mechanisms to carbapenem and fluoroquinolones and their association with TTSS virulence genes, covering MDR P. aeruginosa in Brazil, is the largest reported to date. INTRODUCTIONSevere infections such as bloodstream infection and ventilator-associated pneumonia (VAP) due to multidrugresistant (MDR) Pseudomonas aeruginosa result in greater morbidity and mortality, longer hospitalization and higher cost than infections caused by susceptible bacteria (Morales et al., 2012; Suárez et al., 2010;Voor In't Holt et al., 2014), and aspects related to epidemiology and the outcome of patients with these infections may change, resulting in high rates of resistance and as consequence difficulties in treatment (Kang et al., 2005; Lodise et al., 2007).Today, the emergence of MDR P. aeruginosa is a global problem (Sader et al., 2001; Van der Bij et al., 2011, resulting in the ability of this pathogen to develop resistance to almost all available antibiotics, either by selection of mutations in chromosomal genes or from horizontal gene transfer (Breidenstein et al., 2011). In Brazil this problem is hih5ghly significant and some studies show a very high density of antibiotic use, especially of carbapenems and fluoroquinolones (Moreira et al., 2013;Porto et al., 2013). The resistance of P. aeruginosa to carbapenems is higher than 60 % in some Brazilian hospitals ...

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Section: Discussionsupporting

confidence: 91%

supporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular epidemiological survey of the quinolone- and carbapenem-resistant genotype and its association with the type III secretion system in Pseudomonas aeruginosa

Ferreira

Dantas

Faria

et al. 2015

Journal of Medical Microbiology

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Unlocking the Antibacterial Potential of Xanthone from Calophyllum Species: Inhibition of Nucleic Acid Synthesis

Heilman,

Hui,

Mian

et al. 2023

ChemistrySelect

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Plants are valuable resources for the development of novel pharmaceutical products. The increasing threat to global health caused by antibiotic resistance remains a serious concern, driven a need to discover and evaluate novel anti‐bacterial agents. Calophyllum species are known for having excellent biological activity due to its secondary metabolites, such as xanthone. Numerous xanthones have been found to possess anti‐bacterial properties that are effective against plant pathogens, hence can be applied to fight human pathogens. Topoisomerase enzymes (DNA gyrase and topoisomerase IV) are DNA metabolism enzymes that possess distinct roles as unlinking enzymes during DNA replication. Nucleic acid synthesis inhibition reduces bacteria proliferation through the inhibition of topoisomerase enzymes that are essential for bacterial growth. The xanthone isolated from Calophyllum and its anti‐bacterial were discussed in this review. Besides, molecular docking simulations were applied to explore the potential binding mode of xanthones to DNA metabolism enzymes. The docking study displayed that biscaloxanthone is a good topoisomerase enzymes inhibitor compared to their co‐cystalize ligand, novobiocin and BDBM50198240. The complied information and molecular docking simulations suggested that xanthone isolated possesses potential anti‐bacterial agents inhibiting nucleic acid synthesis. Besides, it suggested that the anti‐microbial activity of xanthone contributes from the topoisomerase enzyme‘s inhibition.

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Fluoroquinolone Resistance: Mechanisms, Restrictive Dosing, and Anti-Mutant Screening Strategies for New Compounds

Drlica¹,

Zhao²,

Malik³

et al. 2011

Antibiotic Discovery and Development

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Alterations in the GyrA and GyrB subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa

Cited by 101 publications

References 29 publications

Molecular epidemiological survey of the quinolone- and carbapenem-resistant genotype and its association with the type III secretion system in Pseudomonas aeruginosa

Molecular epidemiological survey of the quinolone- and carbapenem-resistant genotype and its association with the type III secretion system in Pseudomonas aeruginosa

Unlocking the Antibacterial Potential of Xanthone from Calophyllum Species: Inhibition of Nucleic Acid Synthesis

Fluoroquinolone Resistance: Mechanisms, Restrictive Dosing, and Anti-Mutant Screening Strategies for New Compounds

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