Enhanced Production of Phospholipase C and Perfringolysin O (Alpha and Theta Toxins) in a Gatifloxacin-Resistant Strain of
            <i>Clostridium perfringens</i>

Rafii, Fatemeh; Park, Miseon; Bryant, Amy E.; Johnson, Shemedia J.; Wagner, R. Doug

doi:10.1128/aac.01316-07

Cited by 8 publications

(10 citation statements)

References 38 publications

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“…Resistant strains also exhibit physiological changes that are different from wild-type strains. Similarly, we have shown in vitro that one out of five strains of C. perfringens produced a higher amount of toxin in response to gatifloxacin exposure (Rafii et al 2008). The effects of some of the most recently developed fluoroquinolones (garenoxacin, gemifloxacin, and clinafloxacin) on colonic ecology have also been evaluated (Table 4).…”

Section: Fluoroquinolonesmentioning

confidence: 87%

“…Fluoroquinolones have been shown to induce bacteriophages and enhance Shiga toxin production in E. coli O157:H7, which may increase the virulence of this strain (Zhang et al 2000). In our laboratory, one out of five gatifloxacin-resistant Clostridium perfringens strains also had enhanced production of phospholipase C and perfringolysin O (Rafii et al 2008). Subinhibitory concentrations of ampicillin and clindamycin may directly affect adherence of Clostridium difficile by increasing the expression of genes necessary for colonization (Deneve et al 2008).…”

Section: Effects On Bacterial Pathogenicitymentioning

confidence: 98%

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Effects of treatment with antimicrobial agents on the human colonic microflora

Rafii¹

2008

TCRM

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112

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Antimicrobial agents are the most valuable means available for treating bacterial infections. However, the administration of therapeutic doses of antimicrobial agents to patients is a leading cause of disturbance of the normal gastrointestinal microflora. This disturbance results in diminishing the natural defense mechanisms provided by the colonic microbial ecosystem, making the host vulnerable to infection by commensal microorganisms or nosocomial pathogens. In this minireview, the impacts of antimicrobials, individually and in combinations, on the human colonic microflora are discussed.

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Section: Fluoroquinolonesmentioning

confidence: 87%

Section: Effects On Bacterial Pathogenicitymentioning

confidence: 98%

Effects of treatment with antimicrobial agents on the human colonic microflora

Rafii¹

2008

TCRM

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112

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“…Previously we showed that different C. perfringens strains rapidly developed resistance, even to high potency fluoroquinolones, and that resistant strains had various mutations in the fluoroquinolone target genes [29]. In addition, the production of some enzymes was altered in some resistant mutants [30,31]. One gatifloxacin-resistant strain, NCTR, had increased levels of α-toxin (phospholipase C, PLC) and θ-toxin (perfringolysin O, PFO) [30].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the production of some enzymes was altered in some resistant mutants [30,31]. One gatifloxacin-resistant strain, NCTR, had increased levels of α-toxin (phospholipase C, PLC) and θ-toxin (perfringolysin O, PFO) [30]. These results point to global changes in the expression of various genes in gatifloxacin- resistant strains and to the need for further study.…”

Section: Introductionmentioning

confidence: 99%

Comparative transcription analysis and toxin production of two fluoroquinolone-resistant mutants of Clostridium perfringens

Park

Rafii

2013

BMC Microbiol

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BackgroundFluoroquinolone use has been listed as a risk factor for the emergence of virulent clinical strains of some bacteria. The aim of our study was to evaluate the effect of fluoroquinolone (gatifloxacin) resistance selection on differential gene expression, including the toxin genes involved in virulence, in two fluoroquinolone-resistant strains of Clostridium perfringens by comparison with their wild-type isogenic strains.ResultsDNA microarray analyses were used to compare the gene transcription of two wild types, NCTR and ATCC 13124, with their gatifloxacin-resistant mutants, NCTRR and 13124R. Transcription of a variety of genes involved in bacterial metabolism was either higher or lower in the mutants than in the wild types. Some genes, including genes for toxins and regulatory genes, were upregulated in NCTRR and downregulated in 13124R. Transcription analysis by quantitative real-time PCR (qRT-PCR) confirmed the altered expression of many of the genes that were affected differently in the fluoroquinolone-resistant mutants and wild types. The levels of gene expression and enzyme production for the toxins phospholipase C, perfringolysin O, collagenase and clostripain had decreased in 13124R and increased in NCTRR in comparison with the wild types. After centrifugation, the cytotoxicity of the supernatants of NCTRR and 13224R cultures for mouse peritoneal macrophages confirmed the increased cytotoxicity of NCTRR and the decreased cytotoxicity of 13124R in comparison with the respective wild types. Fluoroquinolone resistance selection also affected cell shape and colony morphology in both strains.ConclusionOur results indicate that gatifloxacin resistance selection was associated with altered gene expression in two C. perfringens strains and that the effect was strain-specific. This study clearly demonstrates that bacterial exposure to fluoroquinolones may affect virulence (toxin production) in addition to drug resistance.

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“…25 Resistance to fluoroquinolones also affects the metabolic activities of C. perfringens, including production of toxins. 18,20 Using microarray analysis of gatifloxacinresistant (GR) mutants of C. perfringens strains NCTR and ATCC 13124, we found global changes in the expression of various genes. 15 Transcription of a variety of genes involved in all aspects of bacterial metabolism, including those coding for energy metabolism, transport, and virulence, was affected.…”

Section: Introductionmentioning

confidence: 99%

Effect of Fluoroquinolone Resistance Selection on the Fitness of Three Strains of Clostridium perfringens

Park

Sutherland

Kim

et al. 2013

Microbial Drug Resistance

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Selection of bacterial strains for resistance to antimicrobial agents may affect fitness; and fluoroquinolone resistance has been shown to affect fitness of aerobic and facultative bacteria. The impact on bacterial fitness of resistance selection to three fluoroquinolones was examined in three wild-type strains of Clostridium perfringens: ATCC 13124, ATCC 3626, and NCTR. Selection for resistance to norfloxacin, ciprofloxacin, and gatifloxacin affected the fitness of nine mutant strains differently. In a series of pure cultures grown in the absence of drugs, the growth of each of the mutants was comparable to that of the corresponding wild type. In competition experiments between mutants and isogenic wild types, however, some of the mutants were less fit. The fitness of ciprofloxacin-resistant mutants was comparable for all three strains, but two gatifloxacin-resistant mutants and one norfloxacin-resistant mutant were significantly less fit than the corresponding wild types. We conclude that both the genetic background of the strain and the fluoroquinolone which induced resistance affected the fitness of the resistant mutants. This is the first time that the effect on fitness of resistance to antimicrobial agents has been measured for C. perfringens.

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Enhanced Production of Phospholipase C and Perfringolysin O (Alpha and Theta Toxins) in a Gatifloxacin-Resistant Strain of Clostridium perfringens

Cited by 8 publications

References 38 publications

Effects of treatment with antimicrobial agents on the human colonic microflora

Effects of treatment with antimicrobial agents on the human colonic microflora

Comparative transcription analysis and toxin production of two fluoroquinolone-resistant mutants of Clostridium perfringens

Effect of Fluoroquinolone Resistance Selection on the Fitness of Three Strains of Clostridium perfringens

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