Antibiotic stress-induced modulation of the endoribonucleolytic activity of RNase III and RNase G confers resistance to aminoglycoside antibiotics in Escherichia coli.
Here, we report a resistance mechanism that is induced through the modulation of 16S ribosomal RNA (rRNA) processing on the exposure of Escherichia coli cells to aminoglycoside antibiotics. We observed decreased expression levels of RNase G associated with increased RNase III activity on rng mRNA in a subgroup of E. coli isolates that transiently acquired resistance to low levels of kanamycin or streptomycin. Analyses of 16S rRNA from the aminoglycoside-resistant E. coli cells, in addition to mutagenesis studies, demonstrated that the accumulation of 16S rRNA precursors containing 3-8 extra nucleotides at the 5' terminus, which results from incomplete processing by RNase G, is responsible for the observed aminoglycoside resistance. Chemical protection, mass spectrometry analysis and cell-free translation assays revealed that the ribosomes from rng-deleted E. coli have decreased binding capacity for, and diminished sensitivity to, streptomycin and neomycin, compared with wild-type cells. It was observed that the deletion of rng had similar effects in Salmonella enterica serovar Typhimurium strain SL1344. Our findings suggest that modulation of the endoribonucleolytic activity of RNase III and RNase G constitutes a previously uncharacterized regulatory pathway for adaptive resistance in E. coli and related gram-negative bacteria to aminoglycoside antibiotics.
Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea, Marine Biotechnology Research Division, Korea Institute of Ocean Science and Technology, Ansan 426-744, Republic of Korea, Department of Microbiology, Catholic University of Daegu, School of Medicine, Nam-Gu, Daegu 705-718, Republic of Korea, Department of Chemistry, KAIST, Daejeon 305-701, Republic of Korea, Department of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea and Department of Microbiology, Pusan National University, Busan 609-735, Republic of Korea.
Wooseok
W
Song
Yong-Hak
YH
Kim
Se-Hoon
SH
Sim
Soonhye
S
Hwang
Jung-Hyun
JH
Lee
Younghoon
Y
Lee
Jeehyeon
J
Bae
Jihwan
J
Hwang
Kangseok
K
Lee
D000617:Aminoglycosides / Q000378:metabolism / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism*; D054680:Ribosome Subunits, Small, Bacterial / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D011500:Protein Synthesis Inhibitors; D012322:RNA Precursors; D012336:RNA, Ribosomal, 16S; D004722:Endoribonucleases; C081905:rng protein, E coli; D043244:Ribonuclease III