Selected Literature

Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations.
Akbergenov R, Duscha S, Fritz A-K, Juskeviciene R, Oishi N, Schmitt K, Shcherbakov D, Teo Y, Boukari H, Freihofer P, Isnard-Petit P, Oettinghaus B, Frank S, Thiam K, Rehrauer H, Westhof E, Schacht J, Eckert A, Wolfer D, Böttger EC (2018)
EMBO Rep: Epub ahead of print

Effects of the 1- N-(4-amino-2 S-hydroxybutyryl) and 6'- N-(2-hydroxyethyl) substituents on ribosomal selectivity, cochleotoxicity, and antibacterial activity in the sisomicin class of aminoglycoside antibiotics.
Sonousi A, Sarpe VA, Brilkova M, Schacht J, Vasella A, Böttger EC, Crich D (2018)
ACS Infect Dis 4: 1114-1120

Structure-based design and synthesis of apramycin-paromomycin analogues. Importance of the configuration at the 6′-position and differences between the 6′-amino and hydroxy series.
Mandhapati AR, Yang G, Kato T, Shcherbakov D, Hobbie SN, Vasella A, Böttger EC, Crich D (2017)
J Am Chem Soc 139: 14611-14619  

Development of a novel lead that targets M. tuberculosis polyketide synthase 13.
Aggarwal A, Parai MK, Shetty N, Wallis D, Woolhiser L, Hastings C, Dutta NK, Galaviz S, Dhakal RC, Shrestha R, Wakabayashi S, Walpole C, Matthews D, Floyd D, Scullion P, Riley J, Epemolu O, Norval S, Snavely T, Robertson GT, Rubin EJ, Ioerger TR,  Sirgel FA, van der Merwe R, van Helden PD, Keller P, Böttger EC, Karakousis PC, Lenaerts AJ, Sacchettini JC (2017)
Cell 170: 249-259

N6’, N6’’’ and O4' modifications to neomycin affect ribosomal selectivity without compromising antibacterial activity.
Sati G, Scherbakov D, Hobbie S, Vasella A, Böttger EC, Crich D (2017)
ACS Infect Dis 3: 368-377

Structure-activity relationships of spectinamide antituberculosis agents; a dissection of ribosomal inhibition and native efflux avoidance contributions.
Liu J, Bruhn D, Lee R, Zheng Z, Janusic T, Scherbakov D, Scherman M, Boshoff H, Das S, Raskesh K, Waidyarachchi S, Brewer T, Gracia B, Yang L, Bollinger J, Robertson G, Meibohm B, Lenaerts A, Ainsa J, Böttger EC, Lee R (2017)
ACS Infect Dis 3: 72-88

Non-mutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase.
Freihofer P, Akbergenov R, Teo Y, Juskeviciene R, Anderson DI, Böttger EC (2016)
RNA: 22: 1836-1843

Aminomethyl spectinomycins as novel therapeutics for drug resistant respiratory tract and sexually transmitted bacterial infections.
Bruhn DF, Waidyarachchi SL, Madhura DB, Shcherbakov D, Zheng Z, Liu J, Abdelrahmand YM, Singh AP, Duscha S, Rathi C, Lee RB, Belland RJ, Meibohm B, Rosch JW, Böttger EC, Lee RE (2015)
Science Translational Medicine 7: 288ra75

XBP1 mitigates aminoglycoside-induced endoplasmic reticulum stress and neuronal cell death.
Oishi N, Duscha S, Boukari H, Meyer M, Xie J, Wei G, Roschitzki B, Böttger EC, Schacht J (2015)
Cell Death and Disease 6: e1763

Influence of 4'-O-glycoside constitution and configuration on ribosomal selectivity of paromomycin.
Matsushita T, Chen W, Juskeviciene R, Youjin T, Shcherbakov D, Vasella A, Böttger EC, Crich D (2015)
J Am Chem Soc 137: 7706-7717

Identification and evaluation of improved 4’-O-(alkyl) 4,5-disubstituted 2-deoxystreptamines as next generation aminoglycoside antibiotics.
Duscha S, Boukari H, Shcherbakov D, Salian S, Silva S, Kendall A, Kato T, Vasella A, Böttger EC (2014)
mBio 5: e01827-14

4’-O-substitutions determine selectivity of aminoglycoside antibiotics.
Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, Boukari H, Pathak R, Dubbaka SR, Lang K, Meyer M, Akbergenov R, Freihofer P, Vaddi S, Thommes P, Ramakrishnan V, Vasella A, Böttger EC (2014)
Nature Commun 5: 3112

Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux.
Lee RE, Hurdle JG, Liu J, Bruhn DF, Matt T, Scherman MS, Vaddady PK, Zheng Z, Qi J, Akbergenov R, Das S, Madhura DB, Rathi C, Trivedi A, Villellas C, Lee RB, Rakesh, Waidyarachi SL, Sun D, McNeil MR, Ainsa JA, Boshoff HI, Gonzalez-Juarrero M, Meibohm B, Böttger EC, Lenaerts AJ (2014)
Nature Med 20: 152-158

Importance of the 6'-hydroxy group and its configuration for apramycin activity.
Mandhapati AR, Shcherbakov D, Duscha S, Vasella A, Böttger EC, Crich D (2014)
Chem Med Chem 9: 2074-2083

Synthesis, antiribosomal and antibacterial activity of 4’-O-glycopyranosyl paromomycin aminoglycoside antibiotics.
Chen W, Matsushita T, Shcherbakov D, Boukari H, Vasella A, Böttger EC, Crich D (2014)
Med Chem Comm 5: 1179-1187

In-vivo efficacy of apramycin in murine infection models.
Meyer M, Freihofer P, Scherman M, Teague J, Lenaerts A, Böttger EC (2014)
Antimicrob Agents Chemother 58: 6938-6941

Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin.
Matt T, Ng CL, Lang K, Sha SH, Akbergenov R, Shcherbakov D, Meyer M, Duscha S, Xie J, Dubbaka SR, Perez-Fernandez D, Vasella A, Ramakrishnan V, Schacht J, Böttger EC (2012)
Proc Natl Acad Sci USA 109: 10984-10989

Structure-activity relationships among the kanamycin aminoglycosides: role of ring I hydroxy and amino groups.
Salian S, Matt T, Akbergenov R, Harish S, Meyer M, Duscha S, Shcherbakov D, Bernet BB, Vasella A, Westhof E, Böttger EC (2012)
Antimicrob Agents Chemother 56: 6104-6108

Molecular basis for the selectivity of antituberculosis compounds capreomycin and viomycin.
Akbergenov R, Shcherbakov D, Matt T, Duscha S, Meyer M, Wilson DN, Böttger EC (2011)
Antimicrob Agents Chemother 55: 4712-4717

Phylogenetic sequence variations in bacterial rRNA affect species-specific susceptibility to drugs targeting protein synthesis.
Akshay S, Bertea M, Hobbie SN, Oettinghaus B, Shcherbakov D, Böttger EC, Akbergenov R (2011)
Antimicrob Agents Chemother 55: 4096-4102

Directed mutagenesis of Mycobacterium smegmatis 16S rRNA to reconstruct the in vivo evolution of aminoglycoside resistance in Mycobacterium tuberculosis.
Shcherbakov D, Akbergenov R, Matt T, Sander P, Andersson DI, Böttger EC (2010)
Mol Microbiol 77: 830-840

Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity.
Hobbie SN, Akshay S, Kalapala SK, Bruell CM, Sherbakov D, Böttger EC (2008)
Proc Natl Acad Sci USA 105: 20888-20893

Mitochondrial deafness alleles confer misreading of the genetic code.
Hobbie SN, Bruell CM, Akshay S, Kalapala SK, Scherbakov D, Böttger EC (2008)
Proc Natl Acad Sci USA 105: 3244-3249

Engineering the rRNA decoding site of eukaryotic cytosolic ribosomes in bacteria.
Hobbie SN, Kalapala SK, Akshay S, Bruell C, Dabow S, Vasella A, Sander P, Böttger EC (2007)
Nucleic Acids Res 35: 6086-6093

23S rRNA 2058A to G alteration mediates ketolide resistance in combination with deletion in L22.
Berisio R, Corti N, Pfister P, Yonath A, Böttger EC (2006)
Antimicrob Agents Chemother 50: 3816-3823

23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058>>G.
Pfister P, Corti N, Hobbie S, Bruell C, Zarivach R, Yonath A, Böttger EC (2005)
Proc Natl Acad Sci USA 102: 5180-5185

Essential mechanisms in the catalysis of peptide bond formation on the ribosome.
Beringer M, Bruell C, Xiong L, Pfister P, Katunin VI, Mankin AS, Böttger EC, Rodnina MV (2005)
J Biol Chem 280: 36065-36072