Origins of Yersinia pestis sensitivity to the arylomycin antibiotics and the inhibition of type I signal peptidase.

Abstract:

:Yersinia pestis is the etiologic agent of the plague. Reports of Y. pestis strains that are resistant to each of the currently approved first-line and prophylactic treatments point to the urgent need to develop novel antibiotics with activity against the pathogen. We previously reported that Y. pestis strain KIM6+, unlike most Enterobacteriaceae, is susceptible to the arylomycins, a novel class of natural-product lipopeptide antibiotics that inhibit signal peptidase I (SPase). In this study, we show that the arylomycin activity is conserved against a broad range of Y. pestis strains and confirm that it results from the inhibition of SPase. We next investigated the origins of this unique arylomycin sensitivity and found that it does not result from an increased affinity of the Y. pestis SPase for the antibiotic and that alterations to each component of the Y. pestis lipopolysaccharide-O antigen, core, and lipid A-make at most only a small contribution. Instead, the origins of the sensitivity can be traced to an increased dependence on SPase activity that results from high levels of protein secretion under physiological conditions. These results highlight the potential of targeting protein secretion in cases where there is a heavy reliance on this process and also have implications for the development of the arylomycins as an antibiotic with activity against Y. pestis and potentially other Gram-negative pathogens.

authors

Steed DB,Liu J,Wasbrough E,Miller L,Halasohoris S,Miller J,Somerville B,Hershfield JR,Romesberg FE

doi

10.1128/AAC.00181-15

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

3887-98

issue

7

eissn

0066-4804

issn

1098-6596

pii

AAC.00181-15

journal_volume

59

pub_type

杂志文章
  • Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease.

    abstract::Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated the treatment outcomes of 77 patients with refractory NTM-LD cause...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00011-18

    authors: Jhun BW,Yang B,Moon SM,Lee H,Park HY,Jeon K,Kwon OJ,Ahn J,Moon IJ,Shin SJ,Daley CL,Koh WJ

    更新日期:2018-06-26 00:00:00

  • In vitro antibacterial activity of SM-1652, a new broad-spectrum cephalosporin with antipseudomonal activity.

    abstract::SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bact...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.23.2.195

    authors: Fukasawa M,Noguchi H,Okuda T,Komatsu T,Yano K

    更新日期:1983-02-01 00:00:00

  • Susceptibility to thrombin-induced platelet microbicidal protein is associated with increased fluconazole efficacy against experimental endocarditis due to Candida albicans.

    abstract::Platelet microbicidal proteins (PMPs) are believed to be integral to host defense against endovascular infection. We previously demonstrated that susceptibility to thrombin-induced PMP 1 (tPMP-1) in vitro negatively influences Candida albicans virulence in the rabbit model of infective endocarditis (IE). This study ev...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.8.3051-3056.2004

    authors: Yeaman MR,Cheng D,Desai B,Kupferwasser LI,Xiong YQ,Gank KD,Edwards JE Jr,Bayer AS

    更新日期:2004-08-01 00:00:00

  • In vitro and in vivo activity of ciprofloxacin against enterococci isolated from patients with infective endocarditis.

    abstract::In vitro activity of ciprofloxacin against 27 strains of enterococci was inoculum dependent. Using inocula of 10(5) to 10(6) or 10(7) to 10(8) CFU of enterococci per ml, the MICs for 50 and 90% of strains tested increased from 1 to greater than or equal to 128 micrograms of ciprofloxacin per ml with the higher inoculu...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.31.3.430

    authors: Fernandez-Guerrero M,Rouse MS,Henry NK,Geraci JE,Wilson WR

    更新日期:1987-03-01 00:00:00

  • An Evolutionary Model-Based Approach To Quantify the Genetic Barrier to Drug Resistance in Fast-Evolving Viruses and Its Application to HIV-1 Subtypes and Integrase Inhibitors.

    abstract::Viral pathogens causing global disease burdens are often characterized by high rates of evolutionary changes. The extensive viral diversity at baseline can shorten the time to escape from therapeutic or immune selective pressure and alter mutational pathways. The impact of genotypic background on the barrier to resist...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00539-19

    authors: Theys K,Libin PJK,Van Laethem K,Abecasis AB

    更新日期:2019-07-25 00:00:00

  • Sulfamethoxazole susceptibility of Mycobacterium tuberculosis isolates from HIV-infected Ugandan adults with tuberculosis taking trimethoprim-sulfamethoxazole prophylaxis.

    abstract::Additional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to have in vitro activity against Mycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patie...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01101-15

    authors: Ogwang S,Good CE,Okware B,Nsereko M,Jacobs MR,Boom WH,Bark CM

    更新日期:2015-09-01 00:00:00

  • Correlation between mutations in liaFSR of Enterococcus faecium and MIC of daptomycin: revisiting daptomycin breakpoints.

    abstract::Mutations in liaFSR, a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00509-12

    authors: Munita JM,Panesso D,Diaz L,Tran TT,Reyes J,Wanger A,Murray BE,Arias CA

    更新日期:2012-08-01 00:00:00

  • Phase 1 safety and pharmacokinetic study of chimeric murine-human monoclonal antibody c alpha Stx2 administered intravenously to healthy adult volunteers.

    abstract::Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated c alpha Stx2, that h...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.49.5.1808-1812.2005

    authors: Dowling TC,Chavaillaz PA,Young DG,Melton-Celsa A,O'Brien A,Thuning-Roberson C,Edelman R,Tacket CO

    更新日期:2005-05-01 00:00:00

  • Antimicrobial Effects of β-Lactams on Imipenem-Resistant Ceftazidime-Susceptible Pseudomonas aeruginosa.

    abstract::We studied the resistance mechanism and antimicrobial effects of β-lactams on imipenem-resistant Pseudomonas aeruginosa isolates that were susceptible to ceftazidime as detected by time-kill curve methods. Among 215 P. aeruginosa isolates from hospitalized patients in eight hospitals in the Republic of Korea, 18 isola...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00054-17

    authors: Wi YM,Choi JY,Lee JY,Kang CI,Chung DR,Peck KR,Song JH,Ko KS

    更新日期:2017-05-24 00:00:00

  • Antibacterial synergism of polymyxin B nonapeptide and hydrophobic antibiotics in experimental gram-negative infections in mice.

    abstract::Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diaminobutyric acid from polymyxin B, is considerably less toxic, lacks bactericidal activity, and retains its ability to render gram-negative bacteria susceptible to several antibiotics by permeabilizing their outer membranes. The peptide rendered all 53 ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.38.2.374

    authors: Ofek I,Cohen S,Rahmani R,Kabha K,Tamarkin D,Herzig Y,Rubinstein E

    更新日期:1994-02-01 00:00:00

  • Reduced amoxicillin uptake into human gastric mucosa when gastric juice pH is high.

    abstract::Amoxicillin when administered with gastric acid suppressors has been shown to be effective in eradication of Helicobacter pylori in 50 to 80% of subjects. The aim of this investigator-blind crossover study was to determine if gastric mucosal amoxicillin uptake was affected by increasing gastric juice pH. Fifteen male ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1128/aac.39.9.2084

    authors: Cardaci G,Lambert JR,King RG,Onishi N,Midolo P

    更新日期:1995-09-01 00:00:00

  • Effects of MS-8209, an amphotericin B derivative, on tumor necrosis factor alpha synthesis and human immunodeficiency virus replication in macrophages.

    abstract::Amphotericin B derivatives, such as MS-8209, have been evaluated as a therapeutic approach to human immunodeficiency virus (HIV) infection. We show that MS-8209, like amphotericin B, increases tumor necrosis factor alpha (TNF-alpha) mRNA expression and TNF-alpha production and consequently HIV replication in human mac...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.2.405-407.2000

    authors: Clayette P,Martin M,Beringue V,Dereuddre-Bosquet N,Adjou KT,Seman M,Dormont D

    更新日期:2000-02-01 00:00:00

  • Accumulation of norfloxacin by Bacteroides fragilis.

    abstract::The accumulation of norfloxacin by Bacteroides fragilis NCTC 9343 was determined by the modified fluorescence method. The time required to achieve a steady-state concentration (SSC) after allowing B. fragilis to accumulate norfloxacin in an aerobic or an anaerobic environment was approximately 2 min; the SSC achieved ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.9.2361-2366.2000

    authors: Ricci V,Piddock LJ

    更新日期:2000-09-01 00:00:00

  • Comparative activities of several nucleoside analogs against duck hepatitis B virus in vitro.

    abstract::Duck hepatitis B virus (DHBV) replication in primary duck hepatocytes was monitored by examining the synthesis of both DHBV DNA and DHBV core antigen. Several nucleoside analogs which were previously shown to inhibit the replication of DNA viruses (i.e., herpesviruses) and retroviruses were examined for their inhibito...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.7.1326

    authors: Yokota T,Konno K,Chonan E,Mochizuki S,Kojima K,Shigeta S,de Clercq E

    更新日期:1990-07-01 00:00:00

  • Olorofim Susceptibility Testing of 1,423 Danish Mold Isolates Obtained in 2018-2019 Confirms Uniform and Broad-Spectrum Activity.

    abstract::Olorofim is a novel antifungal drug in phase 2 trials. It has shown promising in vitro activity against various molds, except for Mucorales. Initially, we observed a broad range of EUCAST MICs for Aspergillus fumigatus Here, we explored the MIC variability in more detail and prospectively investigated the susceptibili...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01527-20

    authors: Astvad KMT,Jørgensen KM,Hare RK,Datcu R,Arendrup MC

    更新日期:2020-12-16 00:00:00

  • Enhanced reduction of Helicobacter pylori load in precolonized mice treated with combined famotidine and urease-binding polysaccharides.

    abstract::The present study investigated the effect of a model urease-binding polysaccharide in combination with a histamine H(2) receptor antagonist on Helicobacter pylori colonization in vivo. Euthymic hairless mice were treated daily with dextran sulfate via drinking water and/or famotidine via intragastric gavage starting a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.9.2492-2497.2000

    authors: Icatlo FC Jr,Kimura N,Goshima H,Kodama Y

    更新日期:2000-09-01 00:00:00

  • Identification of a Novel Gene Associated with High-Level β-Lactam Resistance in Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Strain Mu3 and Methicillin-Resistant S. aureus Strain N315.

    abstract::β-Lactam resistance levels vary among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, mediated by chromosomal mutations and exogenous resistance gene mecA However, MRSA resistance mechanisms are incompletely understood. A P440L mutation in the RNA polymerase β' subunit (RpoC) in slow-vancomycin-i...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00712-18

    authors: Matsuo M,Yamamoto N,Hishinuma T,Hiramatsu K

    更新日期:2019-01-29 00:00:00

  • In vitro activity of HSR-903, a new oral quinolone, against bacteria causing respiratory infections.

    abstract::The in vitro activity of HSR-903, an oral quinolone, against 196 recent clinical isolates of respiratory pathogens was evaluated. HSR-903 was 2 to 32 times more active than ofloxacin, ciprofloxacin, and sparfloxacin against Staphylococcus aureus, including methicillin-resistant strains, and Streptococcus pneumoniae an...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.43.7.1767

    authors: Watanabe A,Tokue Y,Takahashi H,Kikuchi T,Kobayashi T,Gomi K,Fujimura S,Nukiwa T

    更新日期:1999-07-01 00:00:00

  • Comparative penetration of cefonicid and cefazolin into the atrial appendage and pericardial fluid of patients undergoing open-heart surgery.

    abstract::The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft surgery. Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various times and assayed for drug content. The concentratio...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.26.3.347

    authors: Dudley MN,Nightingale CH,Drezner AD,Low HB,Quintiliani R

    更新日期:1984-09-01 00:00:00

  • Antimicrobial susceptibilities of clinical isolates of HACEK organisms.

    abstract::The "HACEK" organisms are a group of fastidious Gram-negative bacteria that cause a variety of infections, including infective endocarditis. Antimicrobial susceptibility testing is not universally available, and therapy for these infections is often empirical. We report the antimicrobial susceptibilities of 70 clinica...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00111-13

    authors: Coburn B,Toye B,Rawte P,Jamieson FB,Farrell DJ,Patel SN

    更新日期:2013-04-01 00:00:00

  • Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A.

    abstract::The in vitro antimicrobial activity of O-demethylfortimicin A (ODMF), a derivative of fortimicin A, was compared with those of fortimicin A and gentamicin against a spectrum of 256 organisms. All three antibiotics were active in low concentrations against all strains of Enterobacteriaceae, Acinetobacter sp., and Staph...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.18.5.766

    authors: Girolami RL,Stamm JM

    更新日期:1980-11-01 00:00:00

  • Candida albicans mucin Msb2 is a broad-range protectant against antimicrobial peptides.

    abstract::The human fungal pathogen Candida albicans releases a large glycofragment of the Msb2 surface protein (Msb2*) into the growth environment, which protects against the action of human antimicrobial peptides (AMPs) LL-37 and histatin-5. Quantitation of Msb2*/LL-37 interactions by microscale thermophoresis revealed high-a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00862-13

    authors: Swidergall M,Ernst AM,Ernst JF

    更新日期:2013-08-01 00:00:00

  • Varicella-zoster virus and subcutaneous cytarabine: correlation of in vitro sensitivities to blood levels.

    abstract::The susceptibility of 26 strains of varicella-zoster virus to cytarabine was tested in vitro by measuring reduction in number and size of plaques using human foreskin fibroblast cells. Most strains showed 50% reduction of plaque number by 0.125 mug of cytarabine per ml or less. Cytarabine levels in sera of 12 patients...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.7.3.229

    authors: Zaky DA,Betts RF,Douglas RG Jr,Bengali K,Neil GL

    更新日期:1975-03-01 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

  • In vitro and in vivo activities of a triterpenoid saponin extract (PX-6518) from the plant Maesa balansae against visceral leishmania species.

    abstract::The in vitro and in vivo activities of a mixture of six oleane triterpene saponins, recovered from the methanolic extract of the leaves of the Vietnamese plant Maesa balansae (PX-6518), were evaluated against drug-sensitive visceral Leishmania strains. The in vitro 50% inhibitory concentration (IC(50)) against intrace...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.48.1.130-136.2004

    authors: Maes L,Vanden Berghe D,Germonprez N,Quirijnen L,Cos P,De Kimpe N,Van Puyvelde L

    更新日期:2004-01-01 00:00:00

  • Streptomycin accumulation by Bacillus subtilis requires both a membrane potential and cytochrome aa3.

    abstract::Cytochrome aa3 concentrations in the cytoplasmic membrane of Bacillus subtilis were altered by growth conditions, and the effects on the membrane potential (delta psi) in whole cells were measured. When cytochrome aa3 was absent, the magnitude of delta psi was not diminished by comparison with the delta psi measured i...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.29.1.141

    authors: Arrow AS,Taber HW

    更新日期:1986-01-01 00:00:00

  • Comparative susceptibilities of 173 aerobic and anaerobic bite wound isolates to sparfloxacin, temafloxacin, clarithromycin, and older agents.

    abstract::The in vitro activities of sparfloxacin, temafloxacin, ciprofloxacin, ofloxacin, clarithromycin, erythromycin, tetracycline, cephalothin, penicillin G, and amoxicillin-clavulanic acid against 173 recent clinical bite wound isolates were determined by agar dilution. Sparfloxacin was active against all strains (MIC for ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.5.1150

    authors: Goldstein EJ,Citron DM

    更新日期:1993-05-01 00:00:00

  • Functional characterization of OXA-57, a class D beta-lactamase from Burkholderia pseudomallei.

    abstract::Class D beta-lactamase OXA-57 was identified in a range of isolates of Burkholderia pseudomallei and Burkholderia thailandensis. Comparative kinetic analyses of wild-type and mutant forms of B. pseudomallei OXA-57 are reported. Implications of these data for beta-lactam resistance and the proposed role of Ser-104 in b...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.4.1639-1641.2005

    authors: Keith KE,Oyston PC,Crossett B,Fairweather NF,Titball RW,Walsh TR,Brown KA

    更新日期:2005-04-01 00:00:00

  • UPC2A is required for high-level azole antifungal resistance in Candida glabrata.

    abstract::Candida glabrata, the second most common cause of Candida infections, is associated with high rates of mortality and often exhibits resistance to the azole class of antifungal agents. Upc2 and Ecm22 in Saccharomyces cerevisiae and Upc2 in Candida albicans are the transcriptional regulators of ERG11, the gene encoding ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02217-13

    authors: Whaley SG,Caudle KE,Vermitsky JP,Chadwick SG,Toner G,Barker KS,Gygax SE,Rogers PD

    更新日期:2014-08-01 00:00:00

  • Development of a Multiplex Real-Time PCR Assay for Rapid Detection of Tigecycline Resistance Gene tet(X) Variants from Bacterial, Fecal, and Environmental Samples.

    abstract::We developed a multiplex real-time SYBR green-based PCR assay for rapid detection of tet(X) and its variants, including tet(X1) and tet(X2) and high-level tigecycline resistance genes tet(X3), tet(X4), and tet(X5). We showed that the real-time PCR assay developed had high linearity (R2 ≥ 0.996), sensitivity (low detec...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02292-19

    authors: Fu Y,Liu D,Song H,Liu Z,Jiang H,Wang Y

    更新日期:2020-03-24 00:00:00