Table 1.
Hibernation factors bind some rRNA residues that mutate in drug-resistant ribosomes.
| HPF residues that interact with rRNA residues whose mutations confer bacterial drug resistance | |||||
|---|---|---|---|---|---|
| HPF residue | rRNA contact | Drugs that bind to the rRNA contact | Model organism | Resistance conferring mutations (compared to wild-type strain) | References |
| Arg102 | C795 (16S) | Ede, Kas, Pac | Halobacterium halobium | C795U required 80 times more pactamycin (80 μM) to cause lethality. | Mankin (1997) |
| His8, Ile40, Glu59 | U965 (16S) | Tet, Tig | Helicobacter pylori | A965G produced 100 times more colonies in the presence of 2 μg/mL of tetracycline. | Dailidiene et al. (2002) |
| Ile40, Lys57, Glu59, Ile61, Phe70 | G966 (16S) | Tet, Tig | Escherichia coli | G966U required 4 times more tetracycline or tigecycline to arrest cell growth. | Bauer et al. (2004) and Polikanov et al. (2014) |
| Ser46, Ala48 | U1052 (16S) | Tet, Tig, Neg | Escherichia coli | U1052G required approximately 4.5 times more negamycin to kill 50% of the population. | Cocozaki et al. (2016) |
| Lys26 | U1495 (16S) | Ami, Gen, Hyg B, Neo, Vio | Mycobacterium smegmatis | U1495C and U1495A required 512 times more paromomycin, and lividomycin to arrest cell growth. | Hobbie et al. (2006) |
| Lys26 | C1496 (16S) | Ami, Gen, Hyg B, Neo, Vio | Mycobacterium smegmatis | C1496U required 32 times more hygromycin B to arrest cell growth. | Pfister et al. (2003) |
| Balon residues that interact with rRNA residues whose mutations confer bacterial drug resistance | |||||
|---|---|---|---|---|---|
| Balon residue | rRNA contact | Drugs that bind to the rRNA contact | Model organism | Resistance conferring mutation (compared to wild-type strain) | References |
| Glu26 | C1409 (16S) | Ami, Cap, Gen, Par, The | Thermus thermophilus | C1409G required 200 times more kanamycin to arrest cell growth. | Pfister et al. (2005) |
| Mycobacterium smegmatis | C1409U required at least 16 times more neomycin, gentamicin, tobramycin and kanamycin to arrest cell growth. | Gregory et al. (2005) | |||
| G1491 (16S) | Neo, Par, Cap | Mycobacterium smegmatis | G1491C required at least 512 times more paromomycin and lividomycin to arrest cell growth. | Hobbie et al. (2006) | |
| His27, Pro28 | Mycobacterium smegmatis | G1491A required 64 times more paromomycin to arrest cell growth. | Kalapala et al. (2010) | ||
| Mycobacterium smegmatis | G1491U required at least 512 times more paromomycin and geneticin to arrest cell growth. | Pfister et al. (2005) | |||
| Gly296, Asn344, Asn345, Arg368 | A1067 (23S) | Thi | Escherichia coli | Ribosomes bearing A1067C and A1067U have ~65% lower thiostrepton affinity. | Thompson et al. (1988) |
| Arg368, Tyr369 | A1095 (23S) | Thi | Escherichia coli | Ribosomes bearing A1095U or A1095C have significantly lower affinity for thiostrepton. | Xu et al. (2002) |
| Gly176, Ser177, Asp178 | A2451 (23S) | Car, Chl, Cli, Dal, Pur, Spa, Tia, Vir | Thermus thermophilus | In a disc diffusion assay, A2451U showed no zone of inhibition to tiamulin and chloramphenicol. | Killeavy et al. (2020) |
| Gly176, Ser177 | C2452 (23S) | Car, Chl, Cli, Dal, Pur, Spa, Tia, Vir | Thermus thermophilus | In a disc diffusion assay, C2452U showed no zone of inhibition to tiamulin. | Killeavy et al. (2020) |
| Lys207 | A2469 (23S) | Avi, Eve | Streptococcus pneumoniae | A2469C required at least 16 times more avilamycin to arrest cell growth. | Adrian et al. (2000) |
Here, we list 13 rRNA residues that have the following two characteristics: (i) They participate in binding to both hibernation factors and antibiotics. (ii) And they undergo resistance-conferring mutations in clinical isolates or laboratory engineered bacterial strains. The abbreviations for the antibiotic names in the table are as follows: Ami, amikacin; Avi, avilamycin; Car, carbomycin; Cap, capreomycin; Chl, chloramphenicol; Cli, clindamycin; Dal, dalfopristin; Ede, edeine; Eve, evernimycin; Gen, gentamicin; Hyg, hygromycin B; Kas, kasugamycin; Neg, negamycin; Neo, neomycin; Pac, pactamycin; Par, paromomycin; Pur, puromycin; Spa, sparsomycin; Tet, tetracycline; The, thermorubin; Thi, Thiostrepton; Tia, tiamulin; Tig, tigecycline; Vir, virginiamycin; Vio, viomycin.