Abstract:
:The adaptive resistance of Pseudomonas aeruginosa to aminoglycosides is known to occur during chronic lung infections in cystic fibrosis patients in response to nonlethal concentrations of aminoglycosides. Not only is it difficult to achieve high levels of drug throughout the dehydrated mucus in the lung, but also steep oxygen gradients exist across the mucus layer, further reducing the bactericidal activity of aminoglycosides. In this study, microarray analysis was utilized to examine the gene responses of P. aeruginosa to lethal, inhibitory, and subinhibitory concentrations of tobramycin under aerobic and anaerobic conditions. While prolonged exposure to subinhibitory concentrations of tobramycin caused increased levels of expression predominantly of the efflux pump genes mexXY, the greatest increases in gene expression levels in response to lethal concentrations of tobramycin involved a number of heat shock genes and the PA0779 gene (renamed here asrA), encoding an alternate Lon protease. Microarray analysis of an asrA::luxCDABE transposon mutant revealed that the induction of heat shock genes in response to tobramycin in this mutant was significantly decreased compared to that in the parent strain. The level of expression of asrA was induced from an arabinose-inducible promoter to 35-fold greater than wild-type expression levels in the absence of tobramycin, and this overexpression alone caused an increased expression of the heat shock genes, as determined by quantitative PCR (qPCR). This overexpression of asrA conferred short-term protection against lethal levels (4 μg/ml) of tobramycin but did not affect the tobramycin MIC. The RpoH heat shock sigma factor was found to be involved in the regulation of asrA in response to both heat shock and tobramycin at the posttranscriptional level. The results of this work suggest that the tobramycin concentration has a significant impact on the gene expression of P. aeruginosa, with lethal concentrations resulting in immediate adaptations conferring short-term protection, such as the induction of the heat shock response, and with subinhibitory concentrations leading to more sustainable long-term protection mechanisms, such as increased efflux.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Kindrachuk KN,Fernández L,Bains M,Hancock REdoi
10.1128/AAC.00935-10subject
Has Abstractpub_date
2011-05-01 00:00:00pages
1874-82issue
5eissn
0066-4804issn
1098-6596pii
AAC.00935-10journal_volume
55pub_type
杂志文章abstract::Retrospective analysis of 189 nonredundant strains of Pseudomonas aeruginosa sequentially recovered from the sputum samples of 46 cystic fibrosis (CF) patients over a 10-year period (1998 to 2007) revealed that 53 out of 189 (28%) samples were hypersusceptible to the beta-lactam antibiotic ticarcillin (MIC < or = 4 mi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01024-08
更新日期:2009-05-01 00:00:00
abstract::A novel algorithm designed for the screening of carbapenemase-producing Enterobacteriaceae (CPE), based on faropenem and temocillin disks, was compared to that of the Committee of the Antibiogram of the French Society of Microbiology (CA-SFM), which is based on ticarcillin-clavulanate, imipenem, and temocillin disks. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00796-17
更新日期:2017-07-25 00:00:00
abstract::A novel beta-lactamase gene, blaOXA-61, from Campylobacter jejuni GC015 was cloned and its nucleotide sequence determined. blaOXA-61 encodes a protein of 257 amino acids in which the active-site STFK tetrad and conserved class D beta-lactamase motifs YGN and KTG were identified. A conserved sequence upstream of blaOXA...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.6.2515-2518.2005
更新日期:2005-06-01 00:00:00
abstract::Burkholderia cepacia complex (Bcc) pulmonary infections in people living with cystic fibrosis (CF) are difficult to treat because of the extreme intrinsic resistance of most isolates to a broad range of antimicrobials. Fosmidomycin is an antibacterial and antiparasitic agent that disrupts the isoprenoid biosynthesis p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02705-14
更新日期:2014-09-01 00:00:00
abstract::Mengo virus double-stranded ribonucleic acid (dsRNA) was obtained on a semi-industrial scale from infected cultures of BHK-21 cells grown in suspension. Yield of the extraction and purification operations was small (about 22 mg from 10(11) cells in a 100-liter culture). Physicochemical characterization of this dsRNA g...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.5.590
更新日期:1973-05-01 00:00:00
abstract::Study of the antimicrobial spectrum of valinomycin revealed that, in addition to the gram-positive bacteria reported in literature, Streptococcus pyogenes and Clostridium sporogenes are also susceptible to this antibiotic. The minimal inhibitory concentrations (MIC) of the antibiotic for S. pyogenes grown aerobically ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.1.63
更新日期:1973-01-01 00:00:00
abstract::Posaconazole and itraconazole were more potent inhibitors of ergosterol synthesis, in both intact cells and cell extracts from Absidia corymbifera and Rhizopus oryzae, than voriconazole and fluconazole. Similarly, expression of CYP51 from R. oryzae in Saccharomyces cerevisiae significantly increased resistance to fluc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00747-06
更新日期:2006-11-01 00:00:00
abstract::Mycobacterium kansasii is the second most common mycobacterial cause of lung disease. Standard treatment consists of rifampin, isoniazid, and ethambutol for at least 12 months after negative sputum. Thus, shorter-duration therapies are needed. Moxifloxacin has good MICs for M. kansasii. However, good preclinical model...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04441-14
更新日期:2015-04-01 00:00:00
abstract::Assessment of drug susceptibility has become an integral part of influenza virus surveillance. In this study, we describe the drug resistance profile of influenza A(H3N2) virus, A/Mississippi/05/2011, collected from a patient treated with oseltamivir and detected via surveillance. An MDCK cell-grown isolate of this vi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01364-13
更新日期:2013-12-01 00:00:00
abstract::The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based com...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00073-17
更新日期:2017-06-27 00:00:00
abstract::Eighty-one clinical isolates of Helicobacter pylori showed no resistance to rifampin (MIC range, 0.032 to 2 microg/ml; MIC at which 50% of isolates are inhibited [MIC50], 0.25 microg/ml). The MIC50 of rifabutin was 0.008 microg/ml (n = 16). All resistant laboratory mutants of H. pylori ATCC 43504 showed amino acid exc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.6.1497
更新日期:1999-06-01 00:00:00
abstract::The diversity of tet(S) genetic contexts of 13 enterococci from human, animal, and environmental samples from different geographical areas is reported. The tet(S) gene was linked to either CTn6000 variants of chromosomal location or composite platforms flanked by IS1216 located on plasmids (∼40 to 115 kb). The compara...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00758-12
更新日期:2012-11-01 00:00:00
abstract::Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates are increasingly migrating from livestock into human and animal health care settings. Alternative substances are needed to overcome the drawbacks of currently available drugs used for MRSA eradication. The recombinant bacteriophage end...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00385-18
更新日期:2018-06-26 00:00:00
abstract::Continued research toward the development of new antifungals that act via inhibition of glycosylphosphatidylinositol (GPI) biosynthesis led to the design of E1210. In this study, we assessed the selectivity of the inhibitory activity of E1210 against Candida albicans GWT1 (Orf19.6884) protein, Aspergillus fumigatus GW...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00731-11
更新日期:2012-02-01 00:00:00
abstract::The spectrum of activity of levofloxacin was initially determined against 29 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs. Levofloxacin MICs were 1 to 2 dilutions lower compared with those obtained for ofloxacin and 8 to 64 dilutions lower compared with those obtained for its ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.11.2483
更新日期:1996-11-01 00:00:00
abstract::The pharmacokinetics of zidovudine (ZDV) are established in patients with various stages of human immunodeficiency virus (HIV) disease. This study was conducted to determine the pharmacokinetic parameters of ZDV in patients with asymptomatic HIV infection and liver disease. HIV-infected volunteers with normal renal fu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1128/aac.39.12.2732
更新日期:1995-12-01 00:00:00
abstract::Aspergillus fumigatus is a leading cause of death in immunocompromised patients and a frequent colonizer of the respiratory tracts of asthma and cystic fibrosis (CF) patients. Biofilms enable bacteria and yeasts to persist in infections and can contribute to antimicrobial resistance. We investigated the ability of A. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00234-08
更新日期:2008-11-01 00:00:00
abstract::The global spread of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has been largely associated with sequence type 258 (ST258) and its related variants (clonal group 258 [CG258]). Here we describe the molecular epidemiology of CR-Kp from five tertiary care hospitals in Medellín, the second largest city in Colombia...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.01775-15
更新日期:2015-10-26 00:00:00
abstract::Streptococcus pneumoniae, a major cause of human disease, produces a 17-mer autoinducer peptide pheromone (competence-stimulating peptide [CSP]) for the control of competence for genetic transformation. Due to previous work linking CSP to stress phenotypes, we set up an in vivo sepsis model to assay its effect on viru...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.12.4725-4732.2004
更新日期:2004-12-01 00:00:00
abstract::Colistin is increasingly being utilized against Gram-negative pathogens, including Pseudomonas aeruginosa, resistant to all other antibiotics. Since limited data exist regarding killing by colistin at different initial inocula (CFUo), we evaluated killing of Pseudomonas aeruginosa by colistin at several CFUo and devel...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00881-09
更新日期:2010-05-01 00:00:00
abstract::A 7.7-kilobase BamHI fragment was cloned from the transconjugant of a clinical isolate of Escherichia coli containing a 120-kilobase multiresistance IncC plasmid. The recombinant plasmid conferred resistance to kanamycin, gentamicin, tobramycin, sulfamethoxazole, and trimethoprim. This clone was used to generate a ser...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.1.96
更新日期:1985-07-01 00:00:00
abstract::Teicoplanin is an investigational glycopeptide antibiotic that is structurally and microbiologically similar to vancomycin. Since teicoplanin possesses a very long elimination half-life, the manufacturer suggests that the drug be administered every 12 h for the first day of therapy and once daily thereafter. We studie...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.11.2114
更新日期:1990-11-01 00:00:00
abstract::Methylene blue (MB) represents a promising antimalarial drug candidate for combination therapies against drug-resistant parasite strains. To support and facilitate the application of MB in future field trials, we studied its antiparasitic effects in vitro. MB is active against all blood stages of both chloroquine (CQ)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.11.4592-4597.2005
更新日期:2005-11-01 00:00:00
abstract::The absorption and excretion of equivalent doses of ampicillin, pivampicillin, and amoxycillin were compared in 10 healthy volunteers after administration of these antibiotics in a randomized triple crossover fashion. As recommended, ampicillin and amoxycillin were administered on an empty stomach, whereas pivampicill...
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.6.5.588
更新日期:1974-11-01 00:00:00
abstract::As increasing numbers of colistin-resistant bacteria emerge, new therapies are urgently needed to treat infections caused by these pathogens. The discovery of new combination therapies is one important way to solve such problems. Here, we report that the antitumor drug PFK-158 and its analogs PFK-015 and 3PO can exert...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00271-19
更新日期:2019-06-24 00:00:00
abstract::Sublethal doses of vincristine (VNC) and bacterial lipopolysaccharide (LPS) administered simultaneously to adult male mice resulted in markedly enhanced mortality. All of 10 strains of Pseudomonas aeruginosa tested, 4 of 7 strains of Bacteroides, and 6 of 10 strains of Listeria monocytogenes were able to substitute fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.5.840
更新日期:1976-05-01 00:00:00
abstract::The VanR-VanS two-component system is responsible for inducing resistance to glycopeptide antibiotics in various bacteria. We have performed a comparative study of the VanR-VanS systems from two streptomyces strains, Streptomyces coelicolor and Streptomyces toyocaensis, to characterize how the two proteins cooperate t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01367-15
更新日期:2015-12-28 00:00:00
abstract::Among 158 Candida glabrata bloodstream isolates collected from numerous centers in China, a resistance to fluconazole was seen in 8.9%. Three isolates (1.9%) were resistant to all echinocandins. Multilocus sequence typing (MLST) revealed that sequence type 7 ([ST7] 65.8%) was the most common type, followed by ST3 (7.6...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.00153-18
更新日期:2018-05-25 00:00:00
abstract::The pharmacokinetics, distribution, and plasma and renal clearance of a new aminoglycoside antibiotic, tobramycin, was studied in the treatment of 18 elderly male patients (average age, 69 years) with urinary tract infections. Ten of these patients had normal renal function and eight had impaired renal function of var...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.4.469
更新日期:1973-04-01 00:00:00
abstract::The mechanism(s) of daptomycin (DAP) resistance (DAPr) is incompletely defined. Thickened cell walls (CWs) acting as either a mechanical barrier or an affinity trap for DAP have been purported to be a major contributor to the DAPr phenotype. To this end, we studied an isogenic set of methicillin-resistant Staphylococc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00122-10
更新日期:2010-08-01 00:00:00