Novel Ser79Leu and Ser81Ile substitutions in the quinolone resistance-determining regions of ParC topoisomerase IV and GyrA DNA gyrase subunits from recent fluoroquinolone-resistant Streptococcus pneumoniae clinical isolates.

Abstract:

:Resistance of Streptococcus pneumoniae to fluoroquinolones is caused predominantly by amino acid substitutions at positions Ser79 of ParC and Ser81 of GyrA to either Phe or Tyr encoded in the quinolone resistance-determining regions of the parC topoisomerase IV and gyrA DNA gyrase genes. Analysis of highly resistant clinical isolates identified novel second-step substitutions, Ser79Leu (ParC) and Ser81Ile (GyrA). To determine contributions of these new mutations to fluoroquinolone resistance either alone or in combination with other Ser79/81 alleles, the substitutions Ser79Leu/Phe/Tyr in ParC and Ser81Ile/Phe/Tyr in GyrA were introduced into the R6 background, resulting in 15 isogenic strains. Their level of fluoroquinolone resistance was determined by susceptibility testing for ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin, gemifloxacin, garenoxacin, and norfloxacin. Leu79 and Ile81 alone as well as 79/81Phe/Tyr substitutions did not contribute significantly to resistance, with fluoroquinolone MICs increasing two- to fourfold compared to wild type for all agents tested. Fluoroquinolone MICs for double transformants ParC Ser79Phe/Tyr/Leu-GyrA Ser81Phe/Tyr were uniformly increased by 8- to 64-fold regardless of pairs of amino acid substitutions. However, combinations including Ile81 conferred two- to fourfold-higher levels of resistance than did combinations including any other Ser81 GyrA substitution, thus demonstrating the differential effects of diverse amino acid substitutions at particular hotspots on fluoroquinolone MICs.

authors

Korzheva N,Davies TA,Goldschmidt R

doi

10.1128/AAC.49.6.2479-2486.2005

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

2479-86

issue

6

eissn

0066-4804

issn

1098-6596

pii

49/6/2479

journal_volume

49

pub_type

杂志文章
  • Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis.

    abstract::Infection is one of the most important causes of titanium implant failure in vivo A developing prophylactic method involves the immobilization of antibiotics, especially vancomycin, onto the surface of the titanium implant. However, these methods have a limited effect in curbing multiple bacterial infections due to an...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01766-16

    authors: Nie B,Long T,Ao H,Zhou J,Tang T,Yue B

    更新日期:2016-12-27 00:00:00

  • Downregulation of mitogen-activated protein kinase 1 of Leishmania donovani field isolates is associated with antimony resistance.

    abstract::Emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (VL) on the Indian subcontinent. The mechanisms operating in laboratory-generated strains are somewhat known, but the determinants of clinical antimony resistance are not well understood. By utili...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00736-11

    authors: Ashutosh,Garg M,Sundar S,Duncan R,Nakhasi HL,Goyal N

    更新日期:2012-01-01 00:00:00

  • Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir.

    abstract::We have recently reported an influenza virus neuraminidase inhibitor, RWJ-270201 (BCX-1812), a novel cyclopentane derivative discovered through structure-based drug design. In this paper, we compare the potency of three compounds, RWJ-270201, oseltamivir, and zanamivir, against neuraminidase enzymes from various subty...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.45.4.1162-1167.2001

    authors: Bantia S,Parker CD,Ananth SL,Horn LL,Andries K,Chand P,Kotian PL,Dehghani A,El-Kattan Y,Lin T,Hutchison TL,Montgomery JA,Kellog DL,Babu YS

    更新日期:2001-04-01 00:00:00

  • In vitro activities of penciclovir and acyclovir against herpes simplex virus types 1 and 2.

    abstract::Penciclovir (PCV) and acyclovir are acyclic guanine analogs which inhibit herpes simplex virus (HSV) DNA polymerase. Their 50% infective doses were 0.5 to 0.8 microgram/ml for clinical isolates of HSV-1 and 1.3 to 2.2 micrograms/ml for HSV-2. Furthermore, HSV-infected cultures receiving 2-h pulses of PCV had 2- to 50-...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.9.2037

    authors: Weinberg A,Bate BJ,Masters HB,Schneider SA,Clark JC,Wren CG,Allaman JA,Levin MJ

    更新日期:1992-09-01 00:00:00

  • Pharmacokinetics of cefotetan in normal subjects and patients with impaired renal function.

    abstract::The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.23.1.31

    authors: Ohkawa M,Hirano S,Tokunaga S,Motoi I,Shoda R,Ikeda A,Sugata T,Sawaki M,Shimamura M,Okasho A,Kuroda K

    更新日期:1983-01-01 00:00:00

  • Enhanced in vitro activity of WR99210 in combination with dapsone against Mycobacterium avium complex.

    abstract::WR99210, a dihydrofolate reductase inhibitor, has promising in vitro activity against Mycobacterium avium complex (MAC). The in vitro activities of WR99210 alone and in combination with a fixed concentration of dapsone (0.5 microgram/ml) were evaluated against 35 clinical MAC isolates by a broth dilution method. The M...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.11.2644

    authors: Shah LM,DeStefano MS,Cynamon MH

    更新日期:1996-11-01 00:00:00

  • Exploring ubiquinone biosynthesis inhibition as a strategy for improving atovaquone efficacy in malaria.

    abstract::Atovaquone (AV) acts on the malaria parasite by competing with ubiquinol (UQH2) for its union to the mitochondrial bc1 complex, preventing the ubiquinone-8,9 (UQ) redox recycling, which is a necessary step in pyrimidine biosynthesis. This study focused on UQ biosynthesis in Plasmodium falciparum and adopted proof-of-c...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01516-20

    authors: Verdaguer IB,Crispim M,Zafra CA,Sussmann RAC,Buriticá NL,Melo HR,Azevedo MF,Almeida FG,Kimura EA,Katzin AM

    更新日期:2021-01-25 00:00:00

  • Daptomycin-nonsusceptible vancomycin-intermediate staphylococcus aureus vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole.

    abstract::We report two cases of daptomycin (DAP)-nonsusceptible (DNS) vancomycin-intermediate Staphylococcus aureus (VISA) vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole. Both patients responded rapidly and favorably to this combination. The clinical ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01046-12

    authors: Avery LM,Steed ME,Woodruff AE,Hasan M,Rybak MJ

    更新日期:2012-11-01 00:00:00

  • In vitro and in vivo activities of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae.

    abstract::The in vitro potency and in vivo efficacy of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae were investigated by pharmacokinetic studies with M. pneumoniae-infected hamsters. By using fluoroquinolones, macrolides, and tetracyclines as references, Q-35 was found to possess the greatest mycoplasmacidal activ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.9.1826

    authors: Gohara Y,Arai S,Akashi A,Kuwano K,Tseng CC,Matsubara S,Matumoto M,Furudera T

    更新日期:1993-09-01 00:00:00

  • CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity.

    abstract::Two neuraminidase (NA) inhibitors, zanamivir (Relenza) and oseltamivir phosphate (Tamiflu), have been licensed for the treatment of and prophylaxis against influenza. In this paper, the new potent NA inhibitor R-125489 is reported for the first time. R-125489 inhibited the NA activities of various type A and B influen...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00333-08

    authors: Yamashita M,Tomozawa T,Kakuta M,Tokumitsu A,Nasu H,Kubo S

    更新日期:2009-01-01 00:00:00

  • Selection and Characterization of Rupintrivir-Resistant Norwalk Virus Replicon Cells In Vitro.

    abstract::Human norovirus (HuNoV) is a major cause of nonbacterial gastroenteritis worldwide, yet despite its impact on society, vaccines and antivirals are currently lacking. A HuNoV replicon system has been widely applied to the evaluation of antiviral compounds and has thus accelerated the process of drug discovery against H...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00201-18

    authors: Kitano M,Hosmillo M,Emmott E,Lu J,Goodfellow I

    更新日期:2018-04-26 00:00:00

  • Cefiderocol Resistance in Acinetobacter baumannii: Roles of β-Lactamases, Siderophore Receptors, and Penicillin Binding Protein 3.

    abstract::Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 μg/ml. Cefiderocol resistance could not be explained by β-lactamase activity. Cef...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01221-20

    authors: Malik S,Kaminski M,Landman D,Quale J

    更新日期:2020-10-20 00:00:00

  • In Vivo Pharmacodynamic Evaluation of Omadacycline against Staphylococcus aureus in the Neutropenic Mouse Pneumonia Model.

    abstract::Omadacycline is an effective therapy for community-acquired bacterial pneumonia (CABP). Given its potent activity against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA), we sought to determine the pharmacodynamic activity and target pharmacokinetic/pharmacodynamic (PK/P...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02058-19

    authors: Lepak AJ,Zhao M,Marchillo K,VanHecker J,Andes DR

    更新日期:2020-01-27 00:00:00

  • Efficacies of vancomycin, arbekacin, and gentamicin alone or in combination against methicillin-resistant Staphylococcus aureus in an in vitro infective endocarditis model.

    abstract::We adopted an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VAN), arbekacin (ABK), and gentamicin (GEN) alone or in combination. Using two strains of clinically isolated methicillin-resistant Staphylococcus aureus, one GEN susceptible (GS171) and one GEN resistant (GR153), fibrin...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.12.3768-3773.2003

    authors: Lee DG,Chun HS,Yim DS,Choi SM,Choi JH,Yoo JH,Shin WS,Kang MW

    更新日期:2003-12-01 00:00:00

  • Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle.

    abstract::Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infec...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02929-15

    authors: Serre SB,Jensen SB,Ghanem L,Humes DG,Ramirez S,Li YP,Krarup H,Bukh J,Gottwein JM

    更新日期:2016-05-23 00:00:00

  • Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia.

    abstract::The production of an L1 metallo-β-lactamase and an L2 serine active-site β-lactamase precludes the use of β-lactams for the treatment of Stenotrophomonas maltophilia infections. Preclinical data suggest that cefiderocol is the first approved β-lactam with reliable activity against S. maltophilia, but data on strains r...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00559-20

    authors: Biagi M,Vialichka A,Jurkovic M,Wu T,Shajee A,Lee M,Patel S,Mendes RE,Wenzler E

    更新日期:2020-08-20 00:00:00

  • Antimalarial dyes revisited: xanthenes, azines, oxazines, and thiazines.

    abstract::In 1891 Guttmann and Ehrlich (P. Guttmann and P. Ehrlich, Berlin Klin. Wochenschr. 28:953-956, 1891) were the first to report the antimalarial properties of a synthetic, rather than a natural, material when they described the clinical cure of two patients after oral administration of a thiazine dye, methylene blue. Si...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.12.2671

    authors: Vennerstrom JL,Makler MT,Angerhofer CK,Williams JA

    更新日期:1995-12-01 00:00:00

  • A Staphylococcus xylosus isolate with a new mecC allotype.

    abstract::Recently, a novel variant of mecA known as mecC (mecA(LGA251)) was identified in Staphylococcus aureus isolates from both humans and animals. In this study, we identified a Staphylococcus xylosus isolate that harbors a new allotype of the mecC gene, mecC1. Whole-genome sequencing revealed that mecC1 forms part of a cl...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01882-12

    authors: Harrison EM,Paterson GK,Holden MT,Morgan FJ,Larsen AR,Petersen A,Leroy S,De Vliegher S,Perreten V,Fox LK,Lam TJ,Sampimon OC,Zadoks RN,Peacock SJ,Parkhill J,Holmes MA

    更新日期:2013-03-01 00:00:00

  • Selective antimicrobial modulation of the intestinal tract by norfloxacin in human volunteers and in gnotobiotic mice associated with a human fecal flora.

    abstract::Intestinal endogenous members of the family Enterobacteriaceae were eliminated in 12 human volunteers treated with 400 or 800 mg of oral norfloxacin per day for 5 days. No clones resistant to quinolone derivatives were isolated. Counts of aerotolerant streptococci were affected to various degrees, depending on their s...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.29.6.1047

    authors: Pecquet S,Andremont A,Tancrède C

    更新日期:1986-06-01 00:00:00

  • Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα.

    abstract::Encephalomyocarditis virus (EMCV), like hepatitis C virus (HCV), requires phosphatidylinositol 4-kinase IIIα (PI4KA) for genome replication. Here, we demonstrate that tyrphostin AG1478, a known epidermal growth factor receptor (EGFR) inhibitor, also inhibits PI4KA activity, both in vitro and in cells. AG1478 impaired ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01331-16

    authors: Dorobantu CM,Harak C,Klein R,van der Linden L,Strating JR,van der Schaar HM,Lohmann V,van Kuppeveld FJ

    更新日期:2016-09-23 00:00:00

  • The separated enantiomers of 2'-deoxy-3'-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro.

    abstract::Racemic 2'-deoxy-3'-thiacytidine (BCH 189) is a dideoxycytidine analog having a sulfur atom in place of the 3' carbon. The enantiomers of BCH 189 have been resolved and found to be equipotent in antiviral activity against human immunodeficiency virus types 1 and 2. However, the (-)-enantiomer (3TC) is considerably les...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.1.202

    authors: Coates JA,Cammack N,Jenkinson HJ,Mutton IM,Pearson BA,Storer R,Cameron JM,Penn CR

    更新日期:1992-01-01 00:00:00

  • Comparison of in vitro activity of Sch 21420, a gentamicin B derivative, with those of amikacin, gentamicin, netilmicin, sisomicin, and tobramycin.

    abstract::Sch 21420 is a new aminoglycoside synthesized from gentamicin B. Susceptibility tests with Sch 21420, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin were performed on a variety of bacterial species including 44 with known mechanisms of resistance to aminoglycosides. Sch 21420 and amikacin had similar effe...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.18.2.338

    authors: Thornsberry C,Barry AL,Jones RN,Baker CN,Badal RE,Packer RR

    更新日期:1980-08-01 00:00:00

  • In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I.

    abstract::SM-7338, a new carbapenem antibiotic, was demonstrated to have potent antibacterial activity against a broad spectrum of aerobes, including Staphylococcus aureus, beta-hemolytic streptococci, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria spp., members of the family Enterobacteriaceae, Pseudomonas spp., a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.2.215

    authors: Edwards JR,Turner PJ,Wannop C,Withnell ES,Grindey AJ,Nairn K

    更新日期:1989-02-01 00:00:00

  • Cryptosporidium parvum metalloaminopeptidase inhibitors prevent in vitro excystation.

    abstract::Cryptosporidium parvum arginine aminopeptidase (RAP) was studied during in vitro excystation. Specific RAP inhibitors were identified by using C. parvum extracts. Amastatin, a series of alpha-aminoboronic acids, and the chelating agents EDTA and 1,10-phenanthrolene, but not endoproteinase inhibitors, blocked enzymatic...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.12.2781

    authors: Okhuysen PC,Chappell CL,Kettner C,Sterling CR

    更新日期:1996-12-01 00:00:00

  • Effects of rifampin and ketoconazole on pharmacokinetics of morinidazole in healthy chinese subjects.

    abstract::Morinidazole, a 5-nitroimidazole antimicrobial drug, has been approved for the treatment of amoebiasis, trichomoniasis, and anaerobic bacterial infections in China. It was reported that drug-drug interaction happened after the coadministration of ornidazole, an analog of morinidazole, and rifampin or ketoconazole. The...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.03382-14

    authors: Pang X,Zhang Y,Gao R,Zhong K,Zhong D,Chen X

    更新日期:2014-10-01 00:00:00

  • Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases.

    abstract::Selection of resistance to cefamandole has been observed, and the drug has failed to protect animals lethally infected with certain Enterobacteriaceae that appeared to be highly susceptible in vitro. Using spectrophotometric assays, some of these organisms were found to produce beta-lactamases highly active against ce...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.15.6.792

    authors: Sanders CC,Sanders WE Jr

    更新日期:1979-06-01 00:00:00

  • MupB, a new high-level mupirocin resistance mechanism in Staphylococcus aureus.

    abstract::Mupirocin is a topical antibiotic used for the treatment of skin infections and the eradication of methicillin-resistant Staphylococcus aureus carriage. It inhibits bacterial protein synthesis by interfering with isoleucyl-tRNA synthetase activity. High-level mupirocin resistance (MIC of ≥ 512 μg/ml) is mediated by th...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.05325-11

    authors: Seah C,Alexander DC,Louie L,Simor A,Low DE,Longtin J,Melano RG

    更新日期:2012-04-01 00:00:00

  • Aminoglycoside dosing weight correction factors for patients of various body sizes.

    abstract::Prior investigations have suggested the use of a dosing weight correction factor of ideal body weight (IBW) plus 40% excess body weight (EBW, where EBW = total body weight [TBW] - IBW) to determine the weight to use for aminoglycoside dosing in morbidly obese (TBW/IBW ratio, > 2) patients. Little data are available to...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.2.545

    authors: Traynor AM,Nafziger AN,Bertino JS Jr

    更新日期:1995-02-01 00:00:00

  • Candida albicans resistance to 5-fluorocytosine: frequency of partially resistant strains among clinical isolates.

    abstract::Resistance to 5-fluorocytosine was studied in 137 independent Candida albicans clinical isolates. Seventy-eight isolates (57%) were susceptible; 51 isolates (37%) were partially resistant; 8 isolates (6%) were highly resistant. All partially resistant isolates gave rise to variants which were highly resistant. Some su...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.22.5.810

    authors: Defever KS,Whelan WL,Rogers AL,Beneke ES,Veselenak JM,Soll DR

    更新日期:1982-11-01 00:00:00

  • Ability of Candida albicans mutants to induce Staphylococcus aureus vancomycin resistance during polymicrobial biofilm formation.

    abstract::Candida albicans and Staphylococcus aureus form vigorous polymicrobial biofilms in serum, which may serve as the source of coinfection in patients. More importantly, S. aureus is highly resistant to vancomycin during polymicrobial biofilm formation, with no decreases in bacterial viability observed with up to 1,600 mi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00573-10

    authors: Harriott MM,Noverr MC

    更新日期:2010-09-01 00:00:00