Aminoglycoside Antibiotic

2020 ◽  
Author(s):  
Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4343
Author(s):  
Lena Mitousis ◽  
Hannes Maier ◽  
Luka Martinovic ◽  
Andreas Kulik ◽  
Sigrid Stockert ◽  
...  

Tobramycin is a broad-spectrum aminoglycoside antibiotic agent. The compound is obtained from the base-catalyzed hydrolysis of carbamoyltobramycin (CTB), which is naturally produced by the actinomycete Streptoalloteichus tenebrarius. However, the strain uses the same precursors to synthesize several structurally related aminoglycosides. Consequently, the production yields of tobramycin are low, and the compound’s purification is very challenging, costly, and time-consuming. In this study, the production of the main undesired product, apramycin, in the industrial isolate Streptoalloteichus tenebrarius 2444 was decreased by applying the fermentation media M10 and M11, which contained high concentrations of starch and dextrin. Furthermore, the strain was genetically engineered by the inactivation of the aprK gene (∆aprK), resulting in the abolishment of apramycin biosynthesis. In the next step of strain development, an additional copy of the tobramycin biosynthetic gene cluster (BGC) was introduced into the ∆aprK mutant. Fermentation by the engineered strain (∆aprK_1-17L) in M11 medium resulted in a 3- to 4-fold higher production than fermentation by the precursor strain (∆aprK). The phenotypic stability of the mutant without selection pressure was validated. The use of the engineered S. tenebrarius 2444 facilitates a step-saving, efficient, and, thus, more sustainable production of the valuable compound tobramycin on an industrial scale.


1980 ◽  
Vol 33 (8) ◽  
pp. 836-841 ◽  
Author(s):  
TAMIO FUJIWARA ◽  
YASUO TAKAHASHI ◽  
KOICHI MATSUMOTO ◽  
EIJI KONDO

1983 ◽  
Vol 36 (6) ◽  
pp. 651-655 ◽  
Author(s):  
MASASHI AWATA ◽  
SHUZO SATOI ◽  
NAOKI MUTO ◽  
MITSUO HAYASHI ◽  
HITOSHI SAGAI ◽  
...  

2001 ◽  
Vol 204 (2) ◽  
pp. 337-348 ◽  
Author(s):  
S. Coombs ◽  
C.B. Braun ◽  
B. Donovan

Lake Michigan mottled sculpin, Cottus bairdi, exhibit a naturally occurring and unconditioned orienting response that can be triggered by both live prey and chemically inert vibrating spheres, even in blinded animals. CoCl(2)-induced reductions of the orienting response demonstrate that the lateral line is required for this behavior in the absence of non-mechanosensory cues (such as vision), but shed no light on the relative contributions of superficial and canal neuromasts to this behavior. To determine the relative roles of these two subsystems, we measured the frequency with which mottled sculpin oriented towards a small vibrating sphere before and after two treatments: (i) immersion of fish in a solution of gentamicin, an aminoglycoside antibiotic that damages hair cells in canal, but not superficial, neuromasts; and (ii) scraping the skin of the fish, which damages the superficial, but not the canal, neuromasts. To ensure that both superficial and canal neuromasts were adequately stimulated, we tested at different vibration frequencies (10 and 50 Hz) near or at the best frequency for each type of neuromast. At both test frequencies, response rates before treatment were greater than 70 % and were significantly greater than ‘spontaneous’ response frequencies measured in the absence of sphere vibration. Response rates fell to spontaneous levels after 1 day of gentamicin treatment and did not return to pre-treatment levels for 10–15 days. In contrast, response rates stayed approximately the same after superficial neuromasts had been damaged by skin abrasion. Scanning electron microscopy confirmed hair cell damage (loss of apical cilia) in canal, but not superficial, neuromasts of gentamicin-treated animals after as little as 24 h of treatment. The sensory epithelium of canal neuromasts gradually returned to normal, following a time course similar to behavioral loss and recovery of the orienting response, whereas that of superficial neuromasts appeared normal throughout the entire period. This study shows that the orienting response of the mottled sculpin is mediated by canal neuromasts.


1999 ◽  
Vol 34 (12) ◽  
pp. 1417-1420 ◽  
Author(s):  
Bisrat Hailemeskel ◽  
Michael Namanny ◽  
Anthony Wutoh

2013 ◽  
Vol 42 (1) ◽  
pp. 11-19 ◽  
Author(s):  
MZ Alam ◽  
L Regioneiri ◽  
MAS Santos

The synthesis of protein according to genetic code of a gene determines the basis of life and a stable proteome is necessary for cell homeostatis. However, errors occur naturally during translation of protein from its mRNA, which varies from 10-3 to 10-4 per codon. These errors are more frequent in recombinant protein overexpressed in heterologous hosts and affect protein functionality. The increasing amount of nonfunctional protein is often related to mistranslation of a gene under stress. In the present study, Saccharomyces cerevisiae as a host organism to overexpress E. coli lacZ gene fusion with GST to quantify misincorporation of amino acid in GST-? galactosidase recombinant protein. The yeast was treated with various stressors such as ethanol, chromium (CrO3), and aminoglycoside antibiotic - geneticin (G418) to induce protein aggregation. The misincorporation of amino acids was studied in soluble protein fractions by mass-spectrometry to determine how much misincorporation occur. We found that under experimental stress conditions the misincorporation of amino acids ranges from 5.6 ×10-3 to 8 × 10-3, which represents 60-80 fold higher than reported level. DOI: http://dx.doi.org/10.3329/bjas.v42i1.15760 Bang. J. Anim. Sci. 2013. 42 (1): 11-19


2019 ◽  
Vol 476 (5) ◽  
pp. 795-808 ◽  
Author(s):  
Jyoti Singh Tomar ◽  
Rama Krishna Peddinti ◽  
Ramakrishna V. Hosur

AbstractAntibiotic-resistant bacteria pose the greatest threat to human health. Among the list of such bacteria released by WHO, carbapenem-resistant Acinetobacter baumannii, for which almost no treatment exists, tops the list. A. baumannii is one of the most troublesome ESKAPE pathogens and mechanisms that have facilitated its rise as a successful pathogen are not well studied. Efforts in this direction have resulted in the identification of Hpa2-Ab, an uncharacterized histone acetyltransferase enzyme of GNAT superfamily. Here, we show that Hpa2-Ab confers resistance against aminoglycoside antibiotics using Escherichia coli DH5α strains in which Hpa2 gene is expressed. Resistivity for aminoglycoside antibiotics is demonstrated with the help of CLSI-2010 and KB tests. Isothermal titration calorimetry, MALDI and acetylation assays indicate that conferred resistance is an outcome of evolved antibiotic acetylation capacity in this. Hpa2 is known to acetylate nuclear molecules; however, here it is found to cross its boundary and participate in other functions. An array of biochemical and biophysical techniques were also used to study this protein, which demonstrates that Hpa2-Ab is intrinsically oligomeric in nature, exists primarily as a dimer and its interface is mainly stabilized by hydrophobic interactions. Our work demonstrates an evolved survival strategy by A. baumannii and provides insights into the mechanism that facilitates it to rise as a successful pathogen.


2001 ◽  
Vol 276 (26) ◽  
pp. 23929-23936 ◽  
Author(s):  
David D. Boehr ◽  
Paul R. Thompson ◽  
Gerard D. Wright

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