Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Antimicrob Agents Chemother ; 54(3): 1082-93, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20086164

ABSTRACT

This study aimed at elucidating the physiological basis of bacterial antibiotic tolerance. By use of a combined phenotypic and gene knockout approach, exogenous nutrient composition was identified as a crucial environmental factor which could mediate progressive development of tolerance with markedly varied drug specificity and sustainability. Deprivation of amino acids was a prerequisite for tolerance formation, conferring condition-specific phenotypes against inhibitors of cell wall synthesis and DNA replication (ampicillin and ofloxacin, respectively), according to the relative abundances of ammonium salts, phosphate, and nucleobases. Upon further depletion of glucose, this variable phase consistently evolved into a sustainable mode, along with enhanced capacity to withstand the effect of the protein synthesis inhibitor gentamicin. Nevertheless, all phenotypes produced during spontaneous nutrient depletion lacked the sustainable, multidrug-tolerant features exhibited by the stationary-phase population and were attributed to complex interaction between starvation-mediated metabolic and stress protection responses on the basis of the following reasons: (i) the nutrition-dependent tolerance characteristics observed suggested that adaptive biosynthetic mechanisms could suppress but not fully avert tolerance under transient starvation conditions; (ii) formation of specific phenotypes could be inhibited by suppressing protein synthesis prior to nutrient depletion; (iii) bacteriostatic drugs produced only weak tolerance in the absence of starvation signals; and (iv) the attenuation of the stringent and SOS responses, as well as the functionality of other putative tolerance determinants, including rpoS, hipA, glpD, and phoU, could alter the induction requirement and drug specificity of the resultant phenotypes. These data reveal the common physiological grounds characteristic of starvation responses and the onset of antibiotic tolerance in bacteria.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Tolerance , Escherichia coli K12/drug effects , Escherichia coli K12/physiology , Heat-Shock Response , Culture Media/chemistry , Escherichia coli K12/genetics , Escherichia coli K12/growth & development , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Gene Expression Regulation, Bacterial , Microbial Sensitivity Tests
2.
Antimicrob Agents Chemother ; 51(7): 2508-13, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17371822

ABSTRACT

We report on the first occurrence of high-level gentamicin resistance (MICs > or = 512 microg/ml) in seven clinical isolates of Streptococcus pasteurianus from Hong Kong. These seven isolates were confirmed to be the species S. pasteurianus on the basis of nucleotide sequencing of the superoxide dismutase (sodA) gene. Epidemiological data as well as the results of pulse-field gel electrophoresis analysis suggested that the seven S. pasteurianus isolates did not belong to the same clone. Molecular characterization showed that they carried a chromosomal, transposon-borne resistance gene [aac(6')Ie-aph(2'')Ia] which was known to encode a bifunctional aminoglycoside-modifying enzyme. The genetic arrangement of this transposon was similar to that of Tn4001, a transposon previously recovered from Staphylococcus aureus and other gram-positive isolates. Genetic linkage with other resistance elements, such as the ermB gene for erythromycin resistance, was not evident. On the basis of these findings, we suggest that routine screening for high-level gentamicin resistance should be recommended for all clinically significant blood culture isolates. This is to avoid the inadvertent use of short-course combination therapy with penicillin and gentamicin, which may lead to the failure of treatment for endocarditis, the selection of drug-resistant Streptococcus pasteurianus and other gram-positive organisms, as well as the unnecessary usage of gentamicin, a drug with potential toxicity.


Subject(s)
Anti-Bacterial Agents/pharmacology , DNA Transposable Elements/genetics , Drug Resistance, Bacterial/genetics , Gentamicins/pharmacology , Streptococcus/drug effects , Base Sequence , DNA, Bacterial/genetics , Electrophoresis, Gel, Pulsed-Field , Hospitals , Humans , Microbial Sensitivity Tests , Polymerase Chain Reaction , Retrospective Studies , Streptococcus/genetics , Streptococcus/isolation & purification
SELECTION OF CITATIONS
SEARCH DETAIL
...