ampicillin tolerance Dotaz Zobrazit nápovědu
Volatiles produced by bacterial cultures are known to induce regulatory and metabolic alterations in nearby con-specific or heterospecific bacteria, resulting in phenotypic changes including acquisition of antibiotic resistance. We observed unhindered growth of ampicillin-sensitive Serratia rubidaea and S. marcescens on ampicillin-containing media, when exposed to volatiles produced by dense bacterial growth. However, this phenomenon appeared to result from pH increase in the medium caused by bacterial volatiles rather than alterations in the properties of the bacterial cultures, as alkalization of ampicillin-containing culture media to pH 8.5 by ammonia or Tris exhibited the same effects, while pretreatment of bacterial cultures under the same conditions prior to antibiotic exposure did not increase ampicillin resistance. Ampicillin was readily inactivated at pH 8.5, suggesting that observed bacterial growth results from metabolic alteration of the medium, rather than an active change in the target bacterial population (i.e. induction of resistance or tolerance). However, even such seemingly simple mechanism may provide a biologically meaningful basis for protection against antibiotics in microbial communities growing on semi-solid media.
- MeSH
- amoniak metabolismus MeSH
- ampicilin chemie farmakologie MeSH
- antibakteriální látky chemie farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- kultivační média chemie metabolismus MeSH
- mikrobiální testy citlivosti MeSH
- rezistence na ampicilin MeSH
- Serratia účinky léků růst a vývoj metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The nucleotide (p)ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance, and virulence. During amino acid starvation, the Escherichia coli (p)ppGpp synthetase RelA is activated by deacylated tRNA in the ribosomal A-site. An increase in (p)ppGpp is believed to drive the formation of antibiotic-tolerant persister cells, prompting the development of strategies to inhibit (p)ppGpp synthesis. We show that in a biochemical system from purified E. coli components, the antibiotic thiostrepton efficiently inhibits RelA activation by the A-site tRNA. In bacterial cultures, the ribosomal inhibitors thiostrepton, chloramphenicol, and tetracycline all efficiently abolish accumulation of (p)ppGpp induced by the Ile-tRNA synthetase inhibitor mupirocin. This abolishment, however, does not reduce the persister level. In contrast, the combination of dihydrofolate reductase inhibitor trimethoprim with mupirocin, tetracycline, or chloramphenicol leads to ampicillin tolerance. The effect is independent of RelA functionality, specific to β-lactams, and not observed with the fluoroquinolone norfloxacin. These results refine our understanding of (p)ppGpp's role in antibiotic tolerance and persistence and demonstrate unexpected drug interactions that lead to tolerance to bactericidal antibiotics.
- MeSH
- antibakteriální látky farmakologie MeSH
- beta-laktamy farmakologie MeSH
- chloramfenikol farmakologie MeSH
- dihydrofolátreduktasa genetika metabolismus MeSH
- Escherichia coli chemie genetika metabolismus MeSH
- guanosintetrafosfát analogy a deriváty metabolismus MeSH
- isoleucin-tRNA-ligasa genetika MeSH
- lékové interakce MeSH
- ligasy antagonisté a inhibitory genetika metabolismus MeSH
- mupirocin farmakologie MeSH
- proteosyntéza účinky léků MeSH
- ribozomy účinky léků metabolismus MeSH
- RNA transferová genetika metabolismus MeSH
- subcelulární frakce chemie účinky léků metabolismus MeSH
- tetracyklin farmakologie MeSH
- thiostrepton farmakologie MeSH
- tolerance léku * MeSH
- trimethoprim farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mezi nejčastěji předepisovaná antibiotika v ordinacích praktických lékařů patří léky ze skupiny aminopenicilinů. Jsou to vysoce účinná antibiotika, používaná jako základní lék při bakteriálních nákazách dýchacích a močových cest. V ambulantní praxi jsou oblíbena zejména pro svou dobrou toleranci a vhodné dávkovači intervaly. V současné době je pro perorální samostatné použití předepisován prakticky výhradně amoxicilin. Ampicilin je používán v potencovaných aminopenicilinech.
