Inhibition of gene expression and growth by antisense peptide nucleic acids in a multiresistant beta-lactamase-producing Klebsiella pneumoniae strain.


:Klebsiella pneumoniae causes common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance. The emergence and spread of beta-lactamase-producing K. pneumoniae strains highlight the need to develop new therapeutic strategies. In this study, we developed antisense peptide nucleic acids (PNAs) conjugated to the (KFF)(3)K peptide and investigated whether they could mediate gene-specific antisense effects in K. pneumoniae. No outer membrane permeabilization was observed with antisense PNAs when used alone. Antisense peptide-PNAs targeted at two essential genes, gyrA and ompA, were found to be growth inhibitory at concentrations of 20 muM and 40 muM, respectively. Mismatched antisense peptide-PNAs with sequence variations of the gyrA and ompA genes when used as controls were not growth inhibitory. Bactericidal effects exerted by peptide-anti-gyrA PNA and peptide-anti-ompA PNA on cells were observed within 6 h of treatment. The antisense peptide-PNAs specifically inhibited expression of DNA gyrase subunit A and OmpA from the respective targeted genes in a dose-dependent manner. Both antisense peptide-PNAs cured IMR90 cell cultures that were infected with K. pneumoniae (10(4) CFU) in a dose-dependent manner without any noticeable toxicity to the human cells.


Kurupati P,Tan KS,Kumarasinghe G,Poh CL




Has Abstract


2007-03-01 00:00:00














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    abstract::A strain of Staphylococcus aureus was planted on filter membranes placed on Trypticase soy agar (BBL). After incubation, the membranes with growing staphylococci were transferred to Trypticase soy agar containing a subinhibitory concentration of penicillin (one-third minimal inhibitory concentration) and again incubat...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Lorian V

    更新日期:1975-06-01 00:00:00

  • Prevalence of antimicrobial resistance among 723 outpatient clinical isolates of Moraxella catarrhalis in the United States in 1994 and 1995: results of a 30-center national surveillance study.

    abstract::Seven hundred twenty-three isolates of Moraxella catarrhalis obtained from outpatients with a variety of infections in 30 medical centers in the United States between 1 November 1994 and 30 April 1995 were characterized in a central laboratory. The overall rate of beta-lactamase production was 95.3%. When the National...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,多中心研究


    authors: Doern GV,Brueggemann AB,Pierce G,Hogan T,Holley HP Jr,Rauch A

    更新日期:1996-12-01 00:00:00

  • In vitro activity of ampicillin or vancomycin combined with gentamicin or streptomycin against enterococci.

    abstract::Minimum inhibitory and bactericidal concentrations of four antibiotics and their combinations were determined for 38 strains of enterococci by a microtitration tube dilution technique. The drugs were ampicillin, vancomycin, gentamicin, and streptomycin; the combinations were ampicillin-gentamicin, ampicillin-streptomy...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Harwick HJ,Kalmanson GM,Guze LB

    更新日期:1973-10-01 00:00:00

  • The Staphylococcus aureus thiol/oxidative stress global regulator Spx controls trfA, a gene implicated in cell wall antibiotic resistance.

    abstract::S. aureus combats cell wall antibiotic stress by altered gene expression mediated by various environmental signal sensors. In this study, we examined the transcriptional regulation of trfA, a gene related to mecA of Bacillus subtilis encoding an adaptor protein implicated in multiple roles, notably, proteolysis and ge...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Jousselin A,Kelley WL,Barras C,Lew DP,Renzoni A

    更新日期:2013-07-01 00:00:00

  • Cefotaxime: in vitro activity and tentative interpretive standards for disk susceptibility testing.

    abstract::Tested against 9,412 recent clinical isolates, cefotaxime exhibited 8 to 64 times greater activity against the Enterobacteriaceae than did cephalothin and two to four times greater activity against Pseudomonas aeruginosa, but only one-half to one-eighth the activity of cephalothin against staphylococci. Using 420 diff...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Fuchs PC,Barry AL,Thornsberry C,Jones RN,Gavan TL,Gerlach EH,Sommers HM

    更新日期:1980-07-01 00:00:00

  • Moxalactam (LY127935), a new semisynthetic 1-oxa-beta-lactam antibiotic with remarkable antimicrobial activity: in vitro comparison with cefamandole and tobramycin.

    abstract::Moxalactam (LY127935) exhibited greater in vitro activity than cefamandole and tobramycin against clinical isolates of Enterobacteriaceae, Aeromonas hydrophila, and Pseudomonas maltophilia. The activities of the three drugs against other microorganisms were as follows: for staphylococci, cefamandole = tobramycin great...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Jones RN,Fuchs PC,Sommers HM,Gavan TL,Barry AL,Gerlach EH

    更新日期:1980-04-01 00:00:00

  • Activities of Nigerian chewing stick extracts against Bacteroides gingivalis and Bacteroides melaninogenicus.

    abstract::The in vitro activities of extracts of Nigerian chewing sticks against Bacteroides gingivalis and B. melaninogenicus are presented. The greatest inhibitory action was produced by Serindeia werneckei, whereas Fagara zanthoxyloides produced no appreciable inhibitory effect. A generally good correlation was found between...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Rotimi VO,Laughon BE,Bartlett JG,Mosadomi HA

    更新日期:1988-04-01 00:00:00

  • Raltegravir pharmacokinetics in treatment-naive patients is not influenced by race: results from the raltegravir early therapy in African-Americans living with HIV (REAL) study.

    abstract::Racial differences in antiretroviral treatment responses remain incompletely explained and may be a consequence of differential pharmacokinetics (PK) associated with race. Raltegravir, an inhibitor of HIV-1 integrase, is commonly used in the treatment of HIV-infected patients, many of whom are African-American. Howeve...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,随机对照试验


    authors: Wohl DA,Dumond JB,Blevins S,Pittard D,Ragan D,Wang R,Massengale K,Walsh K,Floris-Moore M,Eron JJ Jr,Richardson A,Hudgens MG,Kashuba AD

    更新日期:2013-02-01 00:00:00

  • Characterization of spontaneous, In vitro-selected, rifampin-resistant mutants of Mycobacterium tuberculosis strain H37Rv.

    abstract::Resistance to rifampin in Mycobacterium tuberculosis results from mutations in the gene coding for the beta subunit of RNA polymerase (rpoB). At least 95% of rifampin-resistant isolates have mutations in rpoB, and the mutations are clustered in a small region. About 40 distinct point mutations and in-frame insertions ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Morlock GP,Plikaytis BB,Crawford JT

    更新日期:2000-12-01 00:00:00

  • Bioluminescence and 19F magnetic resonance imaging visualize the efficacy of lysostaphin alone and in combination with oxacillin against Staphylococcus aureus in murine thigh and catheter-associated infection models.

    abstract::Staphylococci are the leading cause of hospital-acquired infections worldwide. Increasingly, they resist antibiotic treatment owing to the development of multiple antibiotic resistance mechanisms in most strains. Therefore, the activity and efficacy of recombinant lysostaphin as a drug against this pathogen have been ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Hertlein T,Sturm V,Lorenz U,Sumathy K,Jakob P,Ohlsen K

    更新日期:2014-01-01 00:00:00

  • Integron-mediated rifampin resistance in Pseudomonas aeruginosa.

    abstract::A new rifampin resistance gene, arr-2, has been found in Pseudomonas aeruginosa. The ARR-2 protein shows 54% amino acid identity to the rifampin ADP-ribosylating transferase encoded by the arr gene from Mycobacterium smegmatis. This arr-2 gene is located on a gene cassette within a class I integron. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Tribuddharat C,Fennewald M

    更新日期:1999-04-01 00:00:00

  • Differential gene expression in auristatin PHE-treated Cryptococcus neoformans.

    abstract::The antifungal pentapeptide auristatin PHE was recently shown to interfere with microtubule dynamics and nuclear and cellular division in the opportunistic pathogen Cryptococcus neoformans. To gain a broader understanding of the cellular response of C. neoformans to auristatin PHE, mRNA differential display (DD) and r...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Woyke T,Berens ME,Hoelzinger DB,Pettit GR,Winkelmann G,Pettit RK

    更新日期:2004-02-01 00:00:00

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Lazardi K,Urbina JA,de Souza W

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  • Antibiotic use before chlamydia and gonorrhea genital and extragenital screening in the sexually transmitted infection clinical setting.

    abstract::Background antibiotic use (i.e., administration of antibiotics not directly related to Chlamydia trachomatis or Neisseria gonorrhoeae infections) has been associated with a lower prevalence of genital C. trachomatis infection in a clinical setting. Associations with specific antibiotic types or with N. gonorrhoeae are...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Dukers-Muijrers NH,van Liere GA,Wolffs PF,Den Heijer C,Werner MI,Hoebe CJ

    更新日期:2015-01-01 00:00:00

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Grewal J,Manavathu EK,Taylor DE

    更新日期:1993-12-01 00:00:00

  • Penetration of cefprozil into middle ear fluid of patients with otitis media.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Shyu WC,Haddad J,Reilly J,Khan WN,Campbell DA,Tsai Y,Barbhaiya RH

    更新日期:1994-09-01 00:00:00

  • Efficacy of amphotericin B or itraconazole in a murine model of central nervous system Aspergillus infection.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Chiller TM,Sobel RA,Luque JC,Clemons KV,Stevens DA

    更新日期:2003-02-01 00:00:00

  • T-8581, a new orally and parenterally active triazole antifungal agent: in vitro and in vivo evaluations.

    abstract::T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the optical density at 630 nm by 80% compared with the optical density at 630 nm of the drug-free control) for Candida albicans were as follows: T-8581, 0.218 micro...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Yotsuji A,Shimizu K,Araki H,Fujimaki K,Nishida N,Hori R,Annen N,Yamamoto S,Hayakawa H,Imaizumi H,Watanbe Y,Narita H

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  • Characterization of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump in Klebsiella pneumoniae and Klebsiella quasipneumoniae from Patients in China.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: He R,Yang Y,Wu Y,Zhong LL,Yang Y,Chen G,Qin M,Liang X,Ahmed MAEE,Lin M,Yan B,Xia Y,Dai M,Chen H,Tian GB

    更新日期:2021-01-20 00:00:00

  • Novel strategy for biofilm inhibition by using small molecules targeting molecular chaperone DnaK.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Arita-Morioka K,Yamanaka K,Mizunoe Y,Ogura T,Sugimoto S

    更新日期:2015-01-01 00:00:00

  • ST-246 inhibits in vivo poxvirus dissemination, virus shedding, and systemic disease manifestation.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Berhanu A,King DS,Mosier S,Jordan R,Jones KF,Hruby DE,Grosenbach DW

    更新日期:2009-12-01 00:00:00

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Swarup V,Ghosh J,Ghosh S,Saxena A,Basu A

    更新日期:2007-09-01 00:00:00

  • Tetracycline resistance in Salmonella enterica subsp. enterica serovar Dublin.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Frech G,Schwarz S

    更新日期:1998-05-01 00:00:00

  • Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Djoko KY,Goytia MM,Donnelly PS,Schembri MA,Shafer WM,McEwan AG

    更新日期:2015-10-01 00:00:00

  • Interaction of azthreonam and related monobactams with beta-lactamases from gram-negative bacteria.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Bush K,Freudenberger JS,Sykes RB

    更新日期:1982-09-01 00:00:00

  • Antimicrobial and antileishmanial activities of hypocrellins A and B.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Ma G,Khan SI,Jacob MR,Tekwani BL,Li Z,Pasco DS,Walker LA,Khan IA

    更新日期:2004-11-01 00:00:00

  • Predictors of mortality in patients with bloodstream infection due to ceftazidime-resistant Klebsiella pneumoniae.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Anderson DJ,Engemann JJ,Harrell LJ,Carmeli Y,Reller LB,Kaye KS

    更新日期:2006-05-01 00:00:00

  • Sustained delivery of commensal bacteria from pod-intravaginal rings.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Gunawardana M,Mullen M,Yoo J,Webster P,Moss JA,Baum MM

    更新日期:2014-01-01 00:00:00

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,随机对照试验


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    更新日期:2011-02-01 00:00:00

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Williams GC,Liu A,Knipp G,Sinko PJ

    更新日期:2002-11-01 00:00:00