Abstract:
:The pyrazinamide (PZA) analog 5-chloropyrazinamide (5-Cl PZA) is active against mycobacterial species, including PZA-resistant strains of Mycobacterium tuberculosis. In M. smegmatis, overexpression of the type 1 fatty acid synthase (FAS I) confers resistance to 5-Cl PZA, a potent FAS I inhibitor. Since M. tuberculosis and M. bovis cannot tolerate FAS I overexpression, 5-Cl PZA resistance mutations have yet to be described for tubercle bacilli. In an attempt to identify other factors that govern the activity of 5-Cl PZA, we selected for 5-Cl PZA-resistant isolates from a library of transposon-mutagenized M. smegmatis isolates. Here, we report that increased expression of the M. smegmatis pyrazinamidase PzaA confers resistance to 5-Cl PZA and susceptibility to PZA in M. smegmatis, M. tuberculosis, and M. bovis. In contrast, while ectopic overexpression of the M. tuberculosis pyrazinamidase PncA increases PZA susceptibility, this amidase does not mediate resistance to 5-Cl PZA. We conclude that PncA-independent turnover of 5-Cl PZA represents a potential mechanism of resistance to this compound for M. tuberculosis, which will likely translate into enhanced PZA susceptibility. Thus, countersusceptibility can be manipulated as a resistance-proofing strategy for PZA-based compounds when these agents are used simultaneously.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Baughn AD,Deng J,Vilchèze C,Riestra A,Welch JT,Jacobs WR Jr,Zimhony Odoi
10.1128/AAC.00529-10subject
Has Abstractpub_date
2010-12-01 00:00:00pages
5323-8issue
12eissn
0066-4804issn
1098-6596pii
AAC.00529-10journal_volume
54pub_type
杂志文章abstract::Seven clinical isolates of Shigella sonnei with reduced susceptibilities to fluoroquinolones (sparfloxacin, ciprofloxacin, and ofloxacin) were obtained. The MICs of fluoroquinolones against these S. sonnei strains were 16 to 32 times higher than those obtained against typical strains that are highly susceptible to the...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.37.11.2486
更新日期:1993-11-01 00:00:00
abstract::Recent evidence supports the contribution of a multidrug efflux mechanism to fluoroquinolone resistance in Streptococcus pneumoniae. In this paper I show that reserpine, an inhibitor of multidrug transporters in gram-positive bacteria, dramatically suppresses the in vitro emergence of ciprofloxacin-resistant variants ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.4.988
更新日期:1999-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.1.128
更新日期:1993-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00250-11
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abstract::A total of 191 soil samples from Hangzhou, China, were submitted to detect non-wild-type (non-WT) Aspergillus fumigatus and its associated mechanisms. There were 2 (4.7%), 13 (12.4%), and 31 (23.1%) isolates identified as non-WT in 2014, 2016, and 2018, respectively. The resistant mutations of TR34/L98H, TR46/Y121F/T2...
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pub_type: 杂志文章
doi:10.1128/AAC.00904-20
更新日期:2020-09-21 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2006-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/aac.46.12.4035-4037.2002
更新日期:2002-12-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2001-12-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03539-14
更新日期:2014-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01267-08
更新日期:2009-10-01 00:00:00
abstract::We found a heterozygous C2857T mutation (R953C) in polymerase gamma (Pol-γ) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-γ mutant binding affinity for dCTP is 8-fold less than that of the wild type. The R953C mutant shows a 4-fold decrease in discrimination of analog nucleotides relative to th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00976-16
更新日期:2016-08-22 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05280-11
更新日期:2012-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.9.2170
更新日期:1999-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03722-14
更新日期:2015-04-01 00:00:00
abstract::A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (K(D) = 12 to 20 muM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00898-07
更新日期:2008-02-01 00:00:00
abstract::The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified ti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.5.630
更新日期:1984-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/AAC.42.9.2440
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:1979-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2017-01-24 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.48.1.69-74.2004
更新日期:2004-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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abstract::Bone concentrations of seven antimicrobial agents were determined after parenteral administration. Antibiotics were administered in large doses at customary intervals for 12 to 20 h before total hip or knee replacement; anticipated levels of each drug were achieved in the serum. Methicillin, carbenicillin, and clindam...
journal_title:Antimicrobial agents and chemotherapy
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abstract::The influence of inhibitors of P-glycoprotein (verapamil [VE], cyclosporine [CY], and GF120918 [GF]) on the cell handling of macrolides (erythromycin [ERY], clarithromycin [CLR], roxithromycin [ROX], azithromycin [AZM], and telithromycin [TEL]) was examined in J774 murine macrophages. The net influx rates of AZM and T...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.3.1047-1051.2003
更新日期:2003-03-01 00:00:00