Functional Characterization of CTX-M-14 and CTX-M-15 β-Lactamases by In Vitro DNA Shuffling.

Abstract:

:This work investigated the molecular events driving the evolution of the CTX-M-type β-lactamases by the use of DNA shuffling of fragments of the blaCTX-M-14 and blaCTX-M-15 genes. Analysis of a total of 51 hybrid enzymes showed that enzymatic activity could be maintained in most cases, yet hybrids that were active possessed fewer amino acid substitutions than those that were inactive, suggesting that point mutations in the constructs rather than reshuffling of the fragments of the two target genes would more likely cause disruption of CTX-M activity. For example, the P67L and L261P changes in a CTX-M-14 fragment could completely abolish the activity of the enzyme on all antibiotics tested. Structural analysis showed that L216 was located in the active-site β sheet and might interact with the adjacent hydrophobic residues to stabilize the active-site β sheet and maintain the integrity of the enzyme active site. Likewise, a single amino acid substitution, E64K, was found to exhibit a significant suppressive effect on CTX-M-15 activity. Structural analysis showed that E64 might form a salt bridge with R44, disruption of which might affect CTX-M-15 activity. Further analysis of the structure-function relationship of a range of mutant enzymes confirmed that, as can be expected, unstable enzymes lose their activity and avoid selective events. These findings suggest that the distal pockets could also contribute to the activity of the enzymes and may be regarded as alternative targets for inhibitor development.

authors

Po KHL,Chan EWC,Chen S

doi

10.1128/AAC.00891-17

subject

Has Abstract

pub_date

2017-11-22 00:00:00

issue

12

eissn

0066-4804

issn

1098-6596

pii

AAC.00891-17

journal_volume

61

pub_type

杂志文章
  • Specific inhibition of the eubacterial DNA ligase by arylamino compounds.

    abstract::All known DNA ligases catalyze the formation of a phosphodiester linkage between adjacent termini in double-stranded DNA via very similar mechanisms. The ligase family can, however, be divided into two classes: eubacterial ligases, which require NAD(+) as a cofactor, and other ligases, from viruses, archaea, and eukar...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.43.11.2766

    authors: Ciarrocchi G,MacPhee DG,Deady LW,Tilley L

    更新日期:1999-11-01 00:00:00

  • Novel Antibiotics May Be Noninferior but Are They Becoming Less Effective?: a Systematic Review.

    abstract::Novel antibiotics approved by noninferiority trials may become less effective over time in two scenarios: (i) the treatment effect in studies of novel antibiotics may be consistently worse than studies of older antibiotics; (ii) when a decreasingly effective control arm is used in a series of noninferiority trials. Ou...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01597-20

    authors: Bai AD,Komorowski AS,Lo CKL,Tandon P,Li XX,Mokashi V,Cvetkovic A,Findlater A,Liang L,Loeb M,Mertz D

    更新日期:2020-10-20 00:00:00

  • HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains.

    abstract::T-20EK is a novel fusion inhibitor designed to have enhanced α-helicity over T-20 (enfuvirtide) through engineered electrostatic interactions between glutamic acid (E) and lysine (K) substitutions. T-20EK efficiently suppresses wild-type and T-20-resistant variants. Here, we selected T-20EK-resistant variants. A combi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00237-13

    authors: Shimane K,Kawaji K,Miyamoto F,Oishi S,Watanabe K,Sakagami Y,Fujii N,Shimura K,Matsuoka M,Kaku M,Sarafianos SG,Kodama EN

    更新日期:2013-08-01 00:00:00

  • Rapid, modified Kirby-Bauer susceptibility test with single, high-concentration antimicrobial disks.

    abstract::A rapid (6-7 hr), modified Kirby-Bauer disk-susceptibility method, by which derivatives of tetrazolium dyes are used to enhance delineation between areas of growth and zones of inhibition, has been developed. Inoculated petri plates, prepared by the Kirby-Bauer method, were sprayed, after 6 to 7 hr of incubation (37 C...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.3.3.418

    authors: Boyle VJ,Fancher ME,Ross RW Jr

    更新日期:1973-03-01 00:00:00

  • Distribution of subclasses mefA and mefE of the mefA gene among clinical isolates of macrolide-resistant (M-phenotype) Streptococcus pneumoniae, viridans group streptococci, and Streptococcus pyogenes.

    abstract::The distribution of subclasses mefA and mefE of the mefA gene among 116 M-phenotype streptococci was as follows: pneumococci (38 strains had mefE and 4 mefA), viridans streptococci (49 mefE and 1 mefA), and Streptococcus pyogenes (24 mefA). Spain(9V)-3-14 and England(14)-9 clones of serotype 14 were dominant among pne...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.2.827-829.2005

    authors: Ardanuy C,Tubau F,Liñares J,Domínguez MA,Pallarés R,Martín R,Spanish Pneumococcal Infection Study Network (G03\/103).

    更新日期:2005-02-01 00:00:00

  • Mechanism of antimalarial action of the synthetic trioxolane RBX11160 (OZ277).

    abstract::RBX11160 (OZ277) is a fully synthetic peroxidic antimalarial in clinical development. To study the possible mechanisms of action of RBX11160, we have examined its ability to inhibit PfATP6, a sarcoplasmic reticulum calcium ATPase and proposed target for semisynthetic peroxidic artemisinin derivatives. RBX11160 inhibit...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01064-06

    authors: Uhlemann AC,Wittlin S,Matile H,Bustamante LY,Krishna S

    更新日期:2007-02-01 00:00:00

  • Ritonavir increases plasma amprenavir (APV) exposure to a similar extent when coadministered with either fosamprenavir or APV.

    abstract::To compare the effect of ritonavir on plasma amprenavir pharmacokinetics, healthy adults received either fosamprenavir (700 mg twice a day [BID]) or amprenavir (600 mg BID) alone and in combination with ritonavir (100 mg BID). Ritonavir increased plasma amprenavir pharmacokinetic parameters to a similar extent when co...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,随机对照试验

    doi:10.1128/AAC.50.4.1578-1580.2006

    authors: Wire MB,Baker KL,Jones LS,Shelton MJ,Lou Y,Thomas GJ,Berrey MM

    更新日期:2006-04-01 00:00:00

  • Enzymatic detachment of Staphylococcus epidermidis biofilms.

    abstract::The gram-positive bacterium Staphylococcus epidermidis is the most common cause of infections associated with catheters and other indwelling medical devices. S. epidermidis produces an extracellular slime that enables it to form adherent biofilms on plastic surfaces. We found that a biofilm-releasing enzyme produced b...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.7.2633-2636.2004

    authors: Kaplan JB,Ragunath C,Velliyagounder K,Fine DH,Ramasubbu N

    更新日期:2004-07-01 00:00:00

  • Molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolated in Nepal.

    abstract::Despite the fact that Nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.06418-11

    authors: Poudel A,Nakajima C,Fukushima Y,Suzuki H,Pandey BD,Maharjan B,Suzuki Y

    更新日期:2012-06-01 00:00:00

  • Bacterial Replication Rate Modulation in Combination with Antimicrobial Therapy: Turning the Microbe against Itself.

    abstract::A major clinical challenge for treating infectious diseases is the duration of antimicrobial therapy required to eradicate the pathogen. We hypothesized that modulation of the bacterial replication rate in the context of an antimicrobial exposure is coupled with the rate and extent of bactericidal effects. Herein we d...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01605-16

    authors: Ambrose PG,VanScoy B,Conde H,McCauley J,Rubino CM,Bhavnani SM

    更新日期:2016-12-27 00:00:00

  • Reconstruction of an active integron recombination site after integration of a gene cassette at a secondary site.

    abstract::As the site of insertion of the aadB gene cassette on pRAY, from a clinical isolate of Acinetobacter, is almost identical to the preferred site on integrons, the composite 59-base element (59-BE) associated with this cassette is potentially recombinationally active. By using a conduction assay to quantitate site activ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.43.10.2538

    authors: Segal H,Francia MV,Lobo JM,Elisha G

    更新日期:1999-10-01 00:00:00

  • Discovery of a novel class of orally active antifungal beta-1,3-D-glucan synthase inhibitors.

    abstract::The echinocandins are a class of semisynthetic natural products that target β-1,3-glucan synthase (GS). Their proven clinical efficacy combined with minimal safety issues has made the echinocandins an important asset in the management of fungal infection in a variety of patient populations. However, the echinocandins ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00432-11

    authors: Walker SS,Xu Y,Triantafyllou I,Waldman MF,Mendrick C,Brown N,Mann P,Chau A,Patel R,Bauman N,Norris C,Antonacci B,Gurnani M,Cacciapuoti A,McNicholas PM,Wainhaus S,Herr RJ,Kuang R,Aslanian RG,Ting PC,Black TA

    更新日期:2011-11-01 00:00:00

  • Induction of DnaK and GroEL heat shock proteins by fluoroquinolones in Escherichia coli.

    abstract::Various fluoroquinolones (norfloxacin, enoxacin, ofloxacin, levofloxacin, and sparfloxacin) induce DnaK and GroEL heat shock proteins in Escherichia coli. The induction is transient, consistent with the kinetics of cellular DNA relaxation. The concentrations of fluoroquinolones required for induction are similar to th...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.1.193

    authors: Mizushima T,Matsuo M,Sekimizu K

    更新日期:1997-01-01 00:00:00

  • NDM-5 carbapenemase-encoding gene in multidrug-resistant clinical isolates of Escherichia coli from Algeria.

    abstract::Here, we report the first autochthonous cases of infections caused by blaNDM-5 New Delhi metallo-β-lactamase-producing Escherichia coli strains recovered from urine and blood specimens of three patients from Algeria between January 2012 and February 2013. The three isolates belong to sequence type 2659 and they coexpr...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02818-13

    authors: Sassi A,Loucif L,Gupta SK,Dekhil M,Chettibi H,Rolain JM

    更新日期:2014-09-01 00:00:00

  • Microbiological aetiology, epidemiology, and clinical profile of prosthetic joint infections: are current antibiotic prophylaxis guidelines effective?

    abstract::Prosthetic joint infections remain a major complication of arthroplasty. At present, local and international guidelines recommend cefazolin as a surgical antibiotic prophylaxis at the time of arthroplasty. This retrospective cohort study conducted across 10 hospitals over a 3-year period (January 2006 to December 2008...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,多中心研究

    doi:10.1128/AAC.06246-11

    authors: Peel TN,Cheng AC,Buising KL,Choong PF

    更新日期:2012-05-01 00:00:00

  • Mechanism of inhibition of duck hepatitis B virus polymerase by (-)-beta-L-2',3'-dideoxy-3'-thiacytidine.

    abstract::We have used the endogenous reverse transcriptase reaction of viral core particles from duck liver to elucidate the mechanism of inhibition of duck hepatitis B virus (DHBV) replication by the nucleoside analog (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC). As is the case in human immunodeficiency virus replication, 3...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.7.1430

    authors: Severini A,Liu XY,Wilson JS,Tyrrell DL

    更新日期:1995-07-01 00:00:00

  • Selection of orally active antifungal agents from 3,5-substituted isoxazolidine derivatives based on acute efficacy-safety profiles.

    abstract::Routine in vitro screening of a new synthetic series of 3,5-substituted 2-methylisoxazolidines revealed that three imidazole analogs (PR 967-248, PR 967-234, and PR 969-566) and, to a lesser extent, a triazole analog (PR 988-399) exerted rather potent antifungal activity against three systemic and four dermatophytic c...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.6.895

    authors: Palmer GC,Ordy MJ,Simmons RD,Strand JC,Radov LA,Mullen GB,Kinsolving CR,St Georgiev V,Mitchell JT,Allen SD

    更新日期:1989-06-01 00:00:00

  • In vitro activities of MK-0826 and 16 other antimicrobials against Bacteroides fragilis group strains.

    abstract::The activity of MK-0826, a new carbapenem, against 309 Bacteroides fragilis group strains was investigated and compared with that of 11 other beta-lactam and 5 non-beta-lactam agents. MK-0826 showed excellent activity (MICs ranged from < or =0.06 to 4 microg/ml). The new carbapenem may be useful in the treatment of mi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.45.8.2372-2374.2001

    authors: Betriu C,Sánchez A,Palau ML,Gómez M,Picazo JJ

    更新日期:2001-08-01 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

  • Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing.

    abstract::In a sample of 6,156 sequences from 4,183 persons, the top 30 patterns of protease inhibitor, nucleoside reverse transcriptase (RT) inhibitor, and nonnucleoside RT inhibitor mutations accounted for 55, 46, and 66%, respectively, of sequences with drug resistance mutations. Characterization of the phenotypic and clinic...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.8.3122-3126.2004

    authors: Rhee SY,Liu T,Ravela J,Gonzales MJ,Shafer RW

    更新日期:2004-08-01 00:00:00

  • Molecular Epidemiology and Genome Dynamics of New Delhi Metallo-β-Lactamase-Producing Extraintestinal Pathogenic Escherichia coli Strains from India.

    abstract::The global dissemination and increasing incidence of carbapenem-resistant, Gram-negative organisms have resulted in acute public health concerns. Here, we present a retrospective multicenter study on molecular characterization of metallo-β-lactamase (MBL)-producing clinical Escherichia coli isolates recovered from ext...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01345-16

    authors: Ranjan A,Shaik S,Mondal A,Nandanwar N,Hussain A,Semmler T,Kumar N,Tiwari SK,Jadhav S,Wieler LH,Ahmed N

    更新日期:2016-10-21 00:00:00

  • Antifungal Susceptibility of the Aspergillus viridinutans Complex: Comparison of Two In Vitro Methods.

    abstract::Cryptic species of Aspergillus fumigatus, including the Aspergillus viridinutans species complex, are increasingly reported to be causes of invasive aspergillosis. Their identification is clinically relevant, as these species frequently have intrinsic resistance to common antifungals. We evaluated the susceptibilities...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01927-17

    authors: Lyskova P,Hubka V,Svobodova L,Barrs V,Dhand NK,Yaguchi T,Matsuzawa T,Horie Y,Kolarik M,Dobias R,Hamal P

    更新日期:2018-03-27 00:00:00

  • Antimicrobial activities of clofazimine and B669 are mediated by lysophospholipids.

    abstract::The susceptibilities of a range of gram-positive and gram-negative microbial pathogens to clofazimine and its analog B669 (0.1 to 32 micrograms/ml), as well as the effects of these agents on membrane phospholipid metabolism in Staphylococcus aureus and Escherichia coli, have been investigated in vitro. Gram-positive b...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.12.2729

    authors: Van Rensburg CE,Jooné GK,O'Sullivan JF,Anderson R

    更新日期:1992-12-01 00:00:00

  • Pilot study of ampicillin-ceftriaxone combination for treatment of orthopedic infections due to Enterococcus faecalis.

    abstract::Serious Enterococcus faecalis infections usually require combination therapy to achieve a bactericidal effect. In orthopedic infections, the prognosis of enterococcal etiology is considered poor, and the use of aminoglycosides is questioned. The ampicillin-ceftriaxone combination has recently been accepted as alternat...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00444-09

    authors: Euba G,Lora-Tamayo J,Murillo O,Pedrero S,Cabo J,Verdaguer R,Ariza J

    更新日期:2009-10-01 00:00:00

  • Once-weekly micafungin therapy is as effective as daily therapy for disseminated candidiasis in mice with persistent neutropenia.

    abstract::The effect of micafungin dose scheduling on the treatment of candidemia is unknown. Neutropenic mice with disseminated Candida glabrata infection were treated with single intraperitoneal micafungin doses of 0 to 100 mg/kg of body weight and sacrificed 7 days later. The maximal decline in kidney fungal burden was 5.8 l...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01337-06

    authors: Gumbo T,Drusano GL,Liu W,Kulawy RW,Fregeau C,Hsu V,Louie A

    更新日期:2007-03-01 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

  • Pharmacokinetics of sparfloxacin and serum bactericidal activity against pneumococci.

    abstract::Sparfloxacin, a new fluorinated quinolone, exhibits higher in vitro activity against pneumococci than do ciprofloxacin and ofloxacin. Since up to 30% of cases of pneumococcal pneumonia are associated with bacteremia, and since an increasing percentage of pneumococci are resistant against penicillin, we studied the ser...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.40.3.776

    authors: Trautmann M,Ruhnke M,Borner K,Wagner J,Koeppe P

    更新日期:1996-03-01 00:00:00

  • Dosing regimen matters: the importance of early intervention and rapid attainment of the pharmacokinetic/pharmacodynamic target.

    abstract::To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have focused on PK/PD relationships evaluated at steady-state drug concentrations. However, a concern with reliance upon steady-state drug concentrations is that it ignores events occurring while the pathogen is exposed to intermittent subopt...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,评审

    doi:10.1128/AAC.05360-11

    authors: Martinez MN,Papich MG,Drusano GL

    更新日期:2012-06-01 00:00:00

  • Different doses of cefetamet pivoxil (Ro 15-8075) in the treatment of acute uncomplicated gonococcal urethritis in men.

    abstract::In an open, dose-finding study, a 100% cure rate was observed in patients suffering from uncomplicated gonococcal urethritis who were treated with a single oral dose of either 1.2 g (n = 10), 0.8 g (n = 11), or 0.4 g (n = 10) of cefetamet pivoxil. The MICs of cefetamet for all gonococcal strains ranged from 0.001 to 0...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.4.674

    authors: Tio TT,Sindhunata IR,Wagenvoort JH,Michel MF,Stolz E

    更新日期:1990-04-01 00:00:00

  • Efficacy of pyrvinium pamoate against Cryptosporidium parvum infection in vitro and in a neonatal mouse model.

    abstract::No effective approved drug therapy exists for Cryptosporidium infection of immunocompromised patients. Here we investigated the nonabsorbed anthelmintic drug pyrvinium pamoate for inhibition of the growth of the intestinal protozoan parasite Cryptosporidium parvum. The concentration of pyrvinium that effected 50% grow...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00207-08

    authors: Downey AS,Chong CR,Graczyk TK,Sullivan DJ

    更新日期:2008-09-01 00:00:00