Antibiotics kill bugs; and about a half of them are doing so by messing up translation. That usually means that the ribosome is stalled at a certain step, be it initiation or elongation or ribosomal recycling.
But it is not always just that. Sometimes antibiotics also mess up the ribosome itself and affect its composition.
Exhibit A: kasugamycin, an antibiotic that inhibits translation initiation in bacteria by interfering with binding of the the initiator tRNA. Amazingly enough, treatment with kasugamycin results in dramatic change in the ribosomal composition which is in turn changing ribosome's functional properties. Several proteins dissociate from the small ribosomal subunit (S1, S2, S6, S12, S18 and S21) which turns the 70S ribosome into a 61S kasugamycin particle. Ribosomal protein S1 is of particular interest here, because it is very important for the mRNA:ribosome interactions and is responsible for A/U rich sequences acting as translational activators.
The S61 particle loses the ability to translate mRNAs with Shine-Dalgarno sequences, while being able to translate leaderless mRNAs, that is the ones starting directly with the initiation codon at the 5'. These leaderless mRNAs can be translated without the help of any initiation factors, by bacterial and eukaryotic ribosomes alike, so it is no surprise that S61 particles, even though compromised can still translate these messages.
What is particularly interesting in the kasugamycin story, it is that loss of the ribosomal proteins can be reconstituted in vitro by simply mixing the drug with the 70S. This means that the effect is direct rather than mediated by the assembly process (see below for an example of the latter effect).
Exhibit B: chloramphenicol and erythromycin. These antibiotics cause defects of the ribosomal assembly, and they seem to be doing so by interfering with the expresion levels of different ribosomal proteins. Here we have Liebig's barrel in action: you interfere with levels of many components you need to have and end up running out of one, the limiting one.
All of the above is highly relevant for people using antibiotics as tools, for instance in microscopy. Chloramphenicol and kasugamycin are widely used to inhibit translation (for instance here and here). It's worth remembering that they are doing much more than that while interpreting your results. Sometimes the tool you use can have much more complicated character than one would anticipate, as I discussed here.
Wilson DN (2009). The A-Z of bacterial translation inhibitors. Critical reviews in biochemistry and molecular biology, 44 (6), 393-433 PMID: 19929179Exhibit A: kasugamycin, an antibiotic that inhibits translation initiation in bacteria by interfering with binding of the the initiator tRNA. Amazingly enough, treatment with kasugamycin results in dramatic change in the ribosomal composition which is in turn changing ribosome's functional properties. Several proteins dissociate from the small ribosomal subunit (S1, S2, S6, S12, S18 and S21) which turns the 70S ribosome into a 61S kasugamycin particle. Ribosomal protein S1 is of particular interest here, because it is very important for the mRNA:ribosome interactions and is responsible for A/U rich sequences acting as translational activators.
The S61 particle loses the ability to translate mRNAs with Shine-Dalgarno sequences, while being able to translate leaderless mRNAs, that is the ones starting directly with the initiation codon at the 5'. These leaderless mRNAs can be translated without the help of any initiation factors, by bacterial and eukaryotic ribosomes alike, so it is no surprise that S61 particles, even though compromised can still translate these messages.
What is particularly interesting in the kasugamycin story, it is that loss of the ribosomal proteins can be reconstituted in vitro by simply mixing the drug with the 70S. This means that the effect is direct rather than mediated by the assembly process (see below for an example of the latter effect).
Exhibit B: chloramphenicol and erythromycin. These antibiotics cause defects of the ribosomal assembly, and they seem to be doing so by interfering with the expresion levels of different ribosomal proteins. Here we have Liebig's barrel in action: you interfere with levels of many components you need to have and end up running out of one, the limiting one.
All of the above is highly relevant for people using antibiotics as tools, for instance in microscopy. Chloramphenicol and kasugamycin are widely used to inhibit translation (for instance here and here). It's worth remembering that they are doing much more than that while interpreting your results. Sometimes the tool you use can have much more complicated character than one would anticipate, as I discussed here.
References:
Schluenzen F, Takemoto C, Wilson DN, Kaminishi T, Harms JM, Hanawa-Suetsugu K, Szaflarski W, Kawazoe M, Shirouzu M, Nierhaus KH, Yokoyama S, & Fucini P (2006). The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation. Nature structural & molecular biology, 13 (10), 871-8 PMID: 16998488
Schuwirth BS, Day JM, Hau CW, Janssen GR, Dahlberg AE, Cate JH, & Vila-Sanjurjo A (2006). Structural analysis of kasugamycin inhibition of translation. Nature structural & molecular biology, 13 (10), 879-86 PMID: 16998486
Kaberdina AC, Szaflarski W, Nierhaus KH, & Moll I (2009). An unexpected type of ribosomes induced by kasugamycin: a look into ancestral times of protein synthesis? Molecular cell, 33 (2), 227-36 PMID: 19187763
Siibak T, Peil L, Dönhöfer A, Tats A, Remm M, Wilson DN, Tenson T, & Remme J (2011). Antibiotic-induced ribosomal assembly defects result from changes in the synthesis of ribosomal proteins. Molecular microbiology, 80 (1), 54-67 PMID: 21320180
Nevo-Dinur K, Nussbaum-Shochat A, Ben-Yehuda S, & Amster-Choder O (2011). Translation-independent localization of mRNA in E. coli. Science (New York, N.Y.), 331 (6020), 1081-4 PMID: 21350180
Tzareva NV, Makhno VI, & Boni IV (1994). Ribosome-messenger recognition in the absence of the Shine-Dalgarno interactions. FEBS letters, 337 (2), 189-94 PMID: 8287975
Andreev DE, Terenin IM, Dunaevsky YE, Dmitriev SE, & Shatsky IN (2006). A leaderless mRNA can bind to mammalian 80S ribosomes and direct polypeptide synthesis in the absence of translation initiation factors. Molecular and cellular biology, 26 (8), 3164-9 PMID: 16581790
Montero Llopis P, Jackson AF, Sliusarenko O, Surovtsev I, Heinritz J, Emonet T, & Jacobs-Wagner C (2010). Spatial organization of the flow of genetic information in bacteria. Nature, 466 (7302), 77-81 PMID: 20562858
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