Selection of naturally occurring extended-spectrum TEM beta-lactamase variants by fluctuating beta-lactam pressure. 2000

J Blazquez, and M I Morosini, and M C Negri, and F Baquero
Servicio de Microbiología, Hospital Ramón y Cajal, Madrid 28034, Spain. jblazquez@hrc.insalud.es

Despite the large number of in vitro mutations that increase resistance to extended-spectrum cephalosporins in TEM-type beta-lactamases, only a small number occur in naturally occurring enzymes. In nature, and particularly in the hospital, bacteria that contain beta-lactamases encounter simultaneous or consecutive selective pressure with different beta-lactam molecules. All variants obtained by submitting an Escherichia coli strain that contains a bla(TEM-1) gene to fluctuating challenge with both ceftazidime and amoxicillin contained only mutations previously detected in naturally occurring beta-lactamases. Nevertheless, some variants obtained by ceftazidime challenge alone contained mutations never detected in naturally occurring TEM beta-lactamases, suggesting that extended-spectrum TEM variants in hospital isolates result from fluctuating selective pressure with several beta-lactams rather than selection with a single antibiotic.

UI MeSH Term Description Entries
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001618 beta-Lactamases Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. beta-Lactamase,beta Lactamase,beta Lactamases
D012641 Selection, Genetic Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population. Natural Selection,Genetic Selection,Selection, Natural
D017354 Point Mutation A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. Mutation, Point,Mutations, Point,Point Mutations
D047090 beta-Lactams Four-membered cyclic AMIDES, best known for the PENICILLINS based on a bicyclo-thiazolidine, as well as the CEPHALOSPORINS based on a bicyclo-thiazine, and including monocyclic MONOBACTAMS. The BETA-LACTAMASES hydrolyze the beta lactam ring, accounting for BETA-LACTAM RESISTANCE of infective bacteria. beta-Lactam,4-Thia-1-Azabicyclo(3.2.0)Heptanes,4-Thia-1-Azabicyclo(4.2.0)Octanes,beta Lactam,beta Lactams
D018440 beta-Lactam Resistance Nonsusceptibility of bacteria to the action of the beta-lactam antibiotics. Mechanisms responsible for beta-lactam resistance may be degradation of antibiotics by BETA-LACTAMASES, failure of antibiotics to penetrate, or low-affinity binding of antibiotics to targets. beta-Lactam Resistant,beta-Lactamase Resistance,beta-Lactamase Resistant,Resistance, beta-Lactamase,Resistant, beta-Lactamase,beta Lactam Resistance,beta Lactam Resistant,beta Lactamase Resistance,beta Lactamase Resistant

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