Xiao-Su Pan

Streptococcus pneumoniae DNA Gyrase and Topoisomerase IV: Overexpression, Purification, and Differential Inhibition by Fluoroquinolones

Pan, Xiao-Su, Fisher, L. Mark

Streptococcus pneumoniae gyrA and gyrB genes specifying the DNA gyrase subunits have been cloned into pET plasmid vectors under the control of an inducible T7 promoter and have been separately...

Engineering the Specificity of Antibacterial Fluoroquinolones: Benzenesulfonamide Modifications at C-7 of Ciprofloxacin Change Its Primary Target in Streptococcus pneumoniae from Topoisomerase IV to Gyrase

Alovero, Fabiana L., Pan, Xiao-Su, Morris, Julia E., Manzo, Ruben H., Fisher, L. Mark

We have examined the antipneumococcal mechanisms of a series of novel fluoroquinolones that are identical to ciprofloxacin except for the addition of a benzenesulfonylamido group to the C-7...

Quinolone Resistance Mutations in Streptococcus pneumoniae GyrA and ParC Proteins: Mechanistic Insights into Quinolone Action from Enzymatic Analysis, Intracellular Levels, and Phenotypes of Wild-Type and Mutant Proteins

Pan, Xiao-Su, Yague, Genoveva, Fisher, L. Mark

Mutations in DNA gyrase and/or topoisomerase IV genes are frequently encountered in quinolone-resistant mutants of Streptococcus pneumoniae. To investigate the mechanism of their effects at the...

DNA Gyrase and Topoisomerase IV Are Dual Targets of Clinafloxacin Action in Streptococcus pneumoniae

Pan, Xiao-Su, Fisher, L. Mark

We examined the response of Streptococcus pneumoniae 7785 to clinafloxacin, a novel C-8-substituted fluoroquinolone which is being developed as an antipneumococcal agent. Clinafloxacin was highly...

Grepafloxacin, a Dimethyl Derivative of Ciprofloxacin, Acts Preferentially through Gyrase in Streptococcus pneumoniae: Role of the C-5 Group in Target Specificity

Morris, Julia E., Pan, Xiao-Su, Fisher, L. Mark

Grepafloxacin, a 5-methyl-7-piperazinyl-3"-methyl analogue of ciprofloxacin, was used to obtain stepwise-selected mutants of Streptococcus pneumoniae 7785. Analysis of the quinolone...

Cleavable-Complex Formation by Wild-Type and Quinolone-Resistant Streptococcus pneumoniae Type II Topoisomerases Mediated by Gemifloxacin and Other Fluoroquinolones

Yague, Genoveva, Morris, Julia E., Pan, Xiao-Su, Gould, Katherine A., Fisher, L. Mark

Gemifloxacin is a recently developed fluoroquinolone with potent activity against Streptococcus pneumoniae. We show that the drug is more active than moxifloxacin, gatifloxacin, levofloxacin, and...

Small-Colony Mutants of Staphylococcus aureus Allow Selection of Gyrase-Mediated Resistance to Dual-Target Fluoroquinolones

Pan, Xiao-Su, Hamlyn, Penelope J., Talens-Visconti, Raquel, Alovero, Fabiana L., Manzo, Ruben H., Fisher, L. Mark

Fluoroquinolones acting equally through DNA gyrase and topoisomerase IV in vivo are considered desirable in requiring two target mutations for emergence of resistant bacteria. To investigate this...

Mycobacterium tuberculosis DNA Gyrase: Interaction with Quinolones and Correlation with Antimycobacterial Drug Activity

Aubry, Alexandra, Pan, Xiao-Su, Fisher, L. Mark, Jarlier, Vincent, Cambau, Emmanuelle

Genome studies suggest that DNA gyrase is the sole type II topoisomerase and likely the unique target of quinolones in Mycobacterium tuberculosis. Despite the emerging importance of quinolones in the...

Ciprofloxacin Dimers Target Gyrase in Streptococcus pneumoniae

Gould, Katherine A., Pan, Xiao-Su, Kerns, Robert J., Fisher, L. Mark

We have examined the antipneumococcal activities of novel quinolone dimers in which ciprofloxacin was tethered to itself or to pipemidic acid by linkage of C-7 piperazinyl rings. Symmetric...

Streptococcus pneumoniae DNA Gyrase and Topoisomerase IV: Overexpression, Purification, and Differential Inhibition by Fluoroquinolones

Pan, Xiao-Su, Fisher, L. Mark

Streptococcus pneumoniae gyrA and gyrB genes specifying the DNA gyrase subunits have been cloned into pET plasmid vectors under the control of an inducible T7 promoter and have been separately...

Engineering the Specificity of Antibacterial Fluoroquinolones: Benzenesulfonamide Modifications at C-7 of Ciprofloxacin Change Its Primary Target in Streptococcus pneumoniae from Topoisomerase IV to Gyrase

Alovero, Fabiana L., Pan, Xiao-Su, Morris, Julia E., Manzo, Ruben H., Fisher, L. Mark

We have examined the antipneumococcal mechanisms of a series of novel fluoroquinolones that are identical to ciprofloxacin except for the addition of a benzenesulfonylamido group to the C-7...

Quinolone Resistance Mutations in Streptococcus pneumoniae GyrA and ParC Proteins: Mechanistic Insights into Quinolone Action from Enzymatic Analysis, Intracellular Levels, and Phenotypes of Wild-Type and Mutant Proteins

Pan, Xiao-Su, Yague, Genoveva, Fisher, L. Mark

Mutations in DNA gyrase and/or topoisomerase IV genes are frequently encountered in quinolone-resistant mutants of Streptococcus pneumoniae. To investigate the mechanism of their effects at the...

DNA Gyrase and Topoisomerase IV Are Dual Targets of Clinafloxacin Action in Streptococcus pneumoniae

Pan, Xiao-Su, Fisher, L. Mark

We examined the response of Streptococcus pneumoniae 7785 to clinafloxacin, a novel C-8-substituted fluoroquinolone which is being developed as an antipneumococcal agent. Clinafloxacin was highly...

Grepafloxacin, a Dimethyl Derivative of Ciprofloxacin, Acts Preferentially through Gyrase in Streptococcus pneumoniae: Role of the C-5 Group in Target Specificity

Morris, Julia E., Pan, Xiao-Su, Fisher, L. Mark

Grepafloxacin, a 5-methyl-7-piperazinyl-3"-methyl analogue of ciprofloxacin, was used to obtain stepwise-selected mutants of Streptococcus pneumoniae 7785. Analysis of the quinolone...

Cleavable-Complex Formation by Wild-Type and Quinolone-Resistant Streptococcus pneumoniae Type II Topoisomerases Mediated by Gemifloxacin and Other Fluoroquinolones

Yague, Genoveva, Morris, Julia E., Pan, Xiao-Su, Gould, Katherine A., Fisher, L. Mark

Gemifloxacin is a recently developed fluoroquinolone with potent activity against Streptococcus pneumoniae. We show that the drug is more active than moxifloxacin, gatifloxacin, levofloxacin, and...

Small-Colony Mutants of Staphylococcus aureus Allow Selection of Gyrase-Mediated Resistance to Dual-Target Fluoroquinolones

Pan, Xiao-Su, Hamlyn, Penelope J., Talens-Visconti, Raquel, Alovero, Fabiana L., Manzo, Ruben H., Fisher, L. Mark

Fluoroquinolones acting equally through DNA gyrase and topoisomerase IV in vivo are considered desirable in requiring two target mutations for emergence of resistant bacteria. To investigate this...

Mycobacterium tuberculosis DNA Gyrase: Interaction with Quinolones and Correlation with Antimycobacterial Drug Activity

Aubry, Alexandra, Pan, Xiao-Su, Fisher, L. Mark, Jarlier, Vincent, Cambau, Emmanuelle

Genome studies suggest that DNA gyrase is the sole type II topoisomerase and likely the unique target of quinolones in Mycobacterium tuberculosis. Despite the emerging importance of quinolones in the...

Ciprofloxacin Dimers Target Gyrase in Streptococcus pneumoniae

Gould, Katherine A., Pan, Xiao-Su, Kerns, Robert J., Fisher, L. Mark

We have examined the antipneumococcal activities of novel quinolone dimers in which ciprofloxacin was tethered to itself or to pipemidic acid by linkage of C-7 piperazinyl rings. Symmetric...

Breakage-Reunion Domain of Streptococcus pneumoniae Topoisomerase IV: Crystal Structure of a Gram-Positive Quinolone Target

Laponogov, Ivan, Veselkov, Dennis A., Sohi, Maninder K., Pan, Xiao-Su, Achari, Aniruddha, Yang, Cheng, ...

The 2.7 Å crystal structure of the 55-kDa N-terminal breakage-reunion domain of topoisomerase (topo) IV subunit A (ParC) from Streptococcus pneumoniae, the first for the quinolone targets from a...