Search tips
Search criteria

Results 1-25 (606)

Clipboard (0)
Year of Publication
Document Types
1.  In Vivo Selection of Rifamycin-Resistant Clostridium difficile during Rifaximin Therapy 
Antimicrobial Agents and Chemotherapy  2012;56(11):6019-6020.
We report the selection of Clostridium difficile resistant to the rifamycin class of antibiotics in a patient within 32 h of receiving rifaximin for the treatment of recurrent C. difficile diarrhea. Resistance was associated with single nucleotide substitutions within rpoB.
PMCID: PMC3486587  PMID: 22908175
2.  Detailed Mutational Analysis of Vga(A) Interdomain Linker: Implication for Antibiotic Resistance Specificity and Mechanism 
Detailed mutational analysis examines the roles of individual residues of the Vga(A) linker in determining the antibiotic resistance phenotype. It defines a narrowed region of residues 212 to 220 whose composition determines the resistance specificity to lincosamides, pleuromutilins, and/or streptogramins A. From the analogy with the recently described function of the homologous ABC-F protein EttA as a translational factor, we infer that the Vga(A) linker interacts with the ribosome and directly or indirectly affects the binding of the respective antibiotic.
PMCID: PMC4335903  PMID: 25512423
3.  Complete Nucleotide Sequence of the IncN Plasmid Encoding IMP-6 and CTX-M-2 from Emerging Carbapenem-Resistant Enterobacteriaceae in Japan 
We have determined the DNA sequence of Klebsiella pneumoniae multidrug resistance plasmid pKPI-6, which is a self-transmissible IncN-type plasmid. pKPI-6 harboring blaIMP-6 and blaCTX-M-2 confers a stealth-type carbapenem resistance phenotype on members of the family Enterobacteriaceae that is not detectable with imipenem. pKPI-6 is already epidemic in Japan, favoring the dissemination of IMP-6 and CTX-M-2 in members of the family Enterobacteriaceae.
PMCID: PMC4335907  PMID: 25487806
4.  Isolation of VIM-2-Producing Pseudomonas monteilii Clinical Strains Disseminated in a Tertiary Hospital in Northern Spain 
We describe here the occurrence of blaVIM-2 in 10 carbapenem-resistant Pseudomonas monteilii strains isolated from different clinical samples from patients at the University Hospital Marqués de Valdecilla in northern Spain. All the blaVIM-2-harboring P. monteilii isolates possessed a class 1 integron, with the cassette array [intI1_blaVIM-2_aac(6′)-Ib_qacEΔ1_sul1]. Our results show the emergence of VIM-2-producing multidrug-resistant species other than Pseudomonas aeruginosa or Pseudomonas putida in a Spanish hospital. P. monteilii, although sporadically isolated, should also be considered an important metallo-β-lactamase (MBL) reservoir.
PMCID: PMC4335825  PMID: 25421471
5.  Complete Nucleotide Sequences of Two NDM-1-Encoding Plasmids from the Same Sequence Type 11 Klebsiella pneumoniae Strain 
The sequence type 11 Klebsiella pneumoniae strain Kpn-3002cz was confirmed to harbor two NDM-1-encoding plasmids, pB-3002cz and pS-3002cz. pB-3002cz (97,649 bp) displayed extensive sequence similarity with the blaNDM-1-carrying plasmid pKPX-1. pS-3002cz (73,581 bp) was found to consist of an IncR-related sequence (13,535 bp) and a mosaic region (60,046 bp). A 40,233-bp sequence of pS-3002cz was identical to the mosaic region of pB-3002cz, indicating the en bloc acquisition of the NDM-1-encoding region from one plasmid by the other.
PMCID: PMC4335828  PMID: 25421477
6.  Susceptibility Profiles of Amphotericin B and Posaconazole against Clinically Relevant Mucorales Species under Hypoxic Conditions 
The effect of hypoxic conditions on the in vitro efficacy of amphotericin B and posaconazole against Mucorales was evaluated by defining MICs with Etest and broth microdilution and identifying minimal fungicidal concentrations (MFCs). With Etest, oxygen-dependent changes were detected, while the MIC and the MFC determined with broth microdilution remained unaltered with reduced oxygen levels. The observed differences depended on the method used.
PMCID: PMC4335829  PMID: 25451049
7.  Synergistic Activity of Chloroquine with Fluconazole against Fluconazole-Resistant Isolates of Candida Species 
The in vitro activity of chloroquine and the interactions of chloroquine combined with fluconazole against 37 Candida isolates were tested using the broth microdilution, disk diffusion, and Etest susceptibility tests. Synergistic effect was detected with 6 of 9 fluconazole-resistant Candida albicans isolates, with Candida krusei ATCC 6258, and with all 12 fluconazole-resistant Candida tropicalis isolates.
PMCID: PMC4335839  PMID: 25512426
8.  Novel Conjugative Plasmid from Escherichia coli of Swine Origin That Coharbors the Multiresistance Gene cfr and the Extended-Spectrum-β-Lactamase Gene blaCTX-M-14b 
Two porcine Escherichia coli isolates harbored the cfr gene on conjugative plasmids of 38,405 bp (pGXEC6) and 41,646 bp (pGXEC3). In these two plasmids, the cfr gene was located within a 4,612-bp region containing a tnpA-IS26-cfr-IS26-Δhyp element. Plasmid pGXEC3 was almost identical to pGXEC6 except for a 3,235-bp ISEcp1-blaCTX-M-14b insertion. The colocation of the multiresistance cfr gene with an extended-spectrum-β-lactamase gene on a conjugative plasmid may support the dissemination of these genes by coselection.
PMCID: PMC4335840  PMID: 25421479
9.  The Novel Arylamidine T-2307 Maintains In Vitro and In Vivo Activity against Echinocandin-Resistant Candida albicans 
We evaluated the in vitro and in vivo activities of the investigational arylamidine T-2307 against echinocandin-resistant Candida albicans. T-2307 demonstrated potent in vitro activity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistant C. albicans infections.
PMCID: PMC4335842  PMID: 25451054
10.  Genetic Determinants Involved in p-Aminosalicylic Acid Resistance in Clinical Isolates from Tuberculosis Patients in Northern China from 2006 to 2012 
p-Aminosalicylic acid (PAS) is an important compound for treating multidrug-resistant tuberculosis (TB). Previous studies showed that thyA mutations are often related to PAS resistance in clinical isolates. We performed a systematic analysis of isolate genotypes and detected mutations in three folate pathway genes (folC, thyA, and ribD) in 61.1% (127/208) of PAS-resistant isolates, including 11 double mutants. This result expands our knowledge about the distribution and frequency of mutations related to PAS resistance in mycobacterial clinical isolates.
PMCID: PMC4335845  PMID: 25421465
11.  Mechanism of Reduced Vancomycin Susceptibility Conferred by walK Mutation in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain MW2 
Point mutations with unclear molecular mechanisms are often associated with vancomycin resistance in Staphylococcus aureus. Here, we observed that the walK (G223D) mutation caused decreased expression of genes associated with cell wall metabolism, decreased autolytic activity, thickened cell walls, and reduced vancomycin susceptibility. A phosphorylation assay showed that WalK (G223D) exhibited reduced autophosphorylation, which led to reduced phosphorylation of WalR. An electrophoretic mobility shift assay indicated that WalK (G223D)-phosphorylated WalR had a reduced capacity to bind to the atlA promoter.
PMCID: PMC4335861  PMID: 25451044
12.  Evolution of Staphylococcus aureus under Vancomycin Selective Pressure: the Role of the Small-Colony Variant Phenotype 
Staphylococcus aureus small-colony variants (SCVs) often persist despite antibiotic therapy. Against a 108-CFU/ml methicillin-resistant S. aureus (MRSA) (strain COL) population of which 0%, 1%, 10%, 50%, or 100% was an isogenic hemB knockout (Ia48) subpopulation displaying the SCV phenotype, vancomycin achieved maximal reductions of 4.99, 5.39, 4.50, 3.28, and 1.66 log10 CFU/ml over 48 h. Vancomycin at ≥16 mg/liter shifted a population from 50% SCV cells at 0 h to 100% SCV cells at 48 h, which was well characterized by a Hill-type model (R2 > 0.90).
PMCID: PMC4335873  PMID: 25451045
13.  Engineered Cationic Antimicrobial Peptides To Overcome Multidrug Resistance by ESKAPE Pathogens 
Multidrug resistance constitutes a threat to the medical achievements of the last 50 years. In this study, we demonstrated the abilities of two de novo engineered cationic antibiotic peptides (eCAPs), WLBU2 and WR12, to overcome resistance from 142 clinical isolates representing the most common multidrug-resistant (MDR) pathogens and to display a lower propensity to select for resistant bacteria in vitro compared to that with colistin and LL37. The results warrant an exploration of eCAPs for use in clinical settings.
PMCID: PMC4335883  PMID: 25421473
14.  In Vitro and Intracellular Activities of Peptide Deformylase Inhibitor GSK1322322 against Legionella pneumophila Isolates 
GSK1322322, a novel peptide deformylase inhibitor currently in development as an oral and intravenous agent for the treatment of hospitalized community-acquired bacterial pneumonia, showed poor in vitro activity against a panel of 50 Legionella pneumophila strains, with MICs ranging from 1 to 16 μg/ml and an MIC90 of 16 μg/ml, but very potent intracellular activity, with the minimum extracellular concentrations capable of inhibiting intracellular proliferation (MIECs) ranging from 0.12 to 2 μg/ml and 98% of the strains being inhibited by concentrations of ≤1 μg/ml.
PMCID: PMC4291349  PMID: 25348534
15.  High-Content Screening Technology Combined with a Human Granuloma Model as a New Approach To Evaluate the Activities of Drugs against Mycobacterium tuberculosis 
Tuberculosis remains a major health problem due to the emergence of drug-resistant strains of Mycobacterium tuberculosis. Some models have provided valuable information about drug resistance and efficacy; however, the translation of these results into effective human treatments has mostly proven unsuccessful. In this study, we adapted high-content screening (HCS) technology to investigate the activities of antitubercular compounds in the context of an in vitro granuloma model. We observed significant shifts in the MIC50s between the activities of the compounds under extracellular and granuloma conditions.
PMCID: PMC4291390  PMID: 25348525
16.  Antimalarial Activity of Granzyme B and Its Targeted Delivery by a Granzyme B–Single-Chain Fv Fusion Protein 
We present here the first evidence that granzyme B acts against Plasmodium falciparum (50% inhibitory concentration [IC50], 1,590 nM; 95% confidence interval [95% CI], 1,197 to 2,112 nM). We created a novel antimalarial fusion protein consisting of granzyme B fused to a merozoite surface protein 4 (MSP4)-specific single-chain Fv protein (scFv), which targets the enzyme to infected erythrocytes, with up to an 8-fold reduction in the IC50 (176 nM; 95% CI, 154 to 202 nM). This study confirms the therapeutic efficacies of recombinant antibody-mediated antimalarial immunotherapeutics based on granzyme B.
PMCID: PMC4291407  PMID: 25313223
17.  Metallo-β-Lactamase-Producing Bacteroides Species Can Shield Other Members of the Gut Microbiota from Antibiotics 
Antibiotics disrupt the intestinal microbiota, rendering patients vulnerable to colonization by exogenous pathogens. Intermicrobial interactions may attenuate this effect. Incubation with ceftriaxone-resistant, ccrA-positive, β-lactamase-producing Bacteroides strains raised the minimum bactericidal concentration of ceftriaxone required to kill a susceptible Escherichia coli strain (mean change, <0.25 to 29 mg/liter; P = 0.009); incubation with ceftriaxone-resistant but non-β-lactamase-producing Bacteroides strains had no effect. The production of β-lactamase by common members of the intestinal microbiota (Bacteroides) can protect susceptible fellow commensals from β-lactams.
PMCID: PMC4291410  PMID: 25288080
18.  In Vitro Activity of wALADin Benzimidazoles against Different Life Cycle Stages of Plasmodium Parasites 
wALADin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μM, respectively). One of these derivatives inhibited gliding motility of Plasmodium berghei ANKA infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic replication. Hence, wALADin1 benzimidazoles are tools to study gliding motility and potential antiplasmodial drug candidates.
PMCID: PMC4291411  PMID: 25313210
19.  Molecular Characterization of blaNDM-5 Carried on an IncFII Plasmid in an Escherichia coli Isolate from a Nontraveler Patient in Spain 
A carbapenem-resistant Escherichia coli isolate (sequence type 448 [ST448]) was recovered from a urine culture of a female patient with no recent record of traveling. PCR screening identified the presence of blaNDM-5, blaTEM-1, blaOXA-1, blaCMY-42, and rmtB. blaNDM-5 was carried in a conjugative IncFII-type plasmid (90 kb) together with blaTEM-1 and rmtB. The genetic environment of blaNDM-5 showed a structure similar to those of pMC-NDM and pGUE-NDM, identified in Poland and France in E. coli of African and Indian origin, respectively.
PMCID: PMC4291412  PMID: 25313215
20.  Effect of Rifampin and Rifabutin on Serum Itraconazole Levels in Patients with Chronic Pulmonary Aspergillosis and Coexisting Nontuberculous Mycobacterial Infection 
We investigated the effects of rifampin and rifabutin on serum itraconazole levels in patients with chronic pulmonary aspergillosis. Serum itraconazole concentrations were significantly lower in patients who received itraconazole with rifampin (median, 0.1 μg/ml; P < 0.001) or rifabutin (median, 0.34 μg/ml; P < 0.001) than those receiving itraconazole alone (median, 5.92 μg/ml). Concomitant use of rifampin or rifabutin and itraconazole should be avoided in patients with chronic pulmonary aspergillosis and coexisting mycobacterial infections.
PMCID: PMC4291413  PMID: 25313207
21.  Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for the Cryptococcus neoformans-Cryptococcus gattii Species Complex Using the CLSI M27-A3 Broth Microdilution Method 
Epidemiological cutoff values (ECVs) of isavuconazole are not available for Cryptococcus spp. The isavuconazole ECVs based on wild-type (WT) MIC distributions for 438 Cryptococcus neoformans nongenotyped isolates, 870 isolates of genotype VNI, and 406 Cryptococcus gattii isolates from six laboratories and different geographical areas were 0.06, 0.12, and 0.25 μg/ml, respectively. These ECVs may aid in detecting non-WT isolates with reduced susceptibilities to isavuconazole.
PMCID: PMC4291414  PMID: 25313209
22.  Association of Class 1 and 2 Integrons with Multidrug-Resistant Acinetobacter baumannii International Clones and Acinetobacter nosocomialis Isolates 
The Acinetobacter baumannii clonal complex 113/79 (CC113/79) and class 2 integrons predominate in Latin America; a relationship between these characteristics was explored. The presence of integrases was determined in successive hospital Acinetobacter isolates (163 A. baumannii isolates and 72 Acinetobacter nosocomialis isolates). Most isolates had integrons, but class 1 and 2 integrons were present significantly more often in CC109/1 and CC113/79, respectively. The high prevalence of CC113/79 in Latin America may account for the predominance of class 2 integrons.
PMCID: PMC4291415  PMID: 25348522
23.  Overproduction of the MtrCDE Efflux Pump in Neisseria gonorrhoeae Produces Unexpected Changes in Cellular Transcription Patterns 
The global consequence of drug efflux gene overexpression in bacteria has not been specifically analyzed because strains showing high-level expression typically have mutations in genes encoding regulatory proteins that control other genes. Results from a transcriptional profiling study performed with a strain of Neisseria gonorrhoeae that is capable of high-level transcription of the mtrCDE efflux pump operon independently of control by cognate regulatory proteins revealed that its overexpression has ramifications for systems other than drug efflux.
PMCID: PMC4291417  PMID: 25367915
24.  Verapamil Increases the Bactericidal Activity of Bedaquiline against Mycobacterium tuberculosis in a Mouse Model 
Bedaquiline is a newly approved drug for the treatment of multidrug-resistant tuberculosis, but there are concerns about its safety in humans. We found that the coadministration of verapamil with subinhibitory doses of bedaquiline gave the same bactericidal effect in mice as did the full human bioequivalent bedaquiline dosing. Adding verapamil to bedaquiline monotherapy also protected against the development of resistant mutants in vivo. The adjunctive use of verapamil may permit use of lower doses of bedaquiline to be used and thereby reduce its dose-related toxicities in tuberculosis patients.
PMCID: PMC4291418  PMID: 25331694
25.  Surface Glycosaminoglycans Protect Eukaryotic Cells against Membrane-Driven Peptide Bacteriocins 
Enzymatic elimination of surface glycosaminoglycans or inhibition of their sulfation provokes sensitizing of HT-29 and HeLa cells toward the peptide bacteriocins nisin A, plantaricin C, and pediocin PA-1/AcH. The effect can be partially reversed by heparin, which also lowers the susceptibility of Lactococcus lactis to nisin A. These data indicate that the negative charge of the glycosaminoglycan sulfate residues binds the positively charged bacteriocins, thus protecting eukaryotic cells from plasma membrane damage.
PMCID: PMC4291419  PMID: 25331698

Results 1-25 (606)