Disease relevance of Neomycin E

• Occlusive paromomycin for cutaneous leishmaniasis [1].
• The absence of RAC or Ssb1/2p results in a similar set of phenotypes, including hypersensitivity against the aminoglycoside paromomycin, which binds to the small ribosomal subunit and compromises the fidelity of translation [2].
• Prospective trial of paromomycin for cryptosporidiosis in AIDS [3].
• A small RNA derived from the decoding region of Escherichia coli 16S rRNA can bind to antibiotics of aminoglycosides (neomycin and paromomycin) that act on the small ribosomal subunit [Purohit,P. and Stern,S. (1994) Nature, 370, 659-662] [4].
• Paromomycin is a promising therapy for cryptosporidiosis in acquired immunodeficiency syndrome and further prospective clinical trials are warranted [5].

Psychiatry related information on Neomycin E

• Thus, paromomycin is an effective alternative to conventional multi-drug therapy for intestinal amebiasis, and it has the advantages of low toxicity, brief duration of therapy, and a high rate of patient compliance [6].

High impact information on Neomycin E

• GCN1 expression conferred sensitivity to paromomycin in a manner dependent on its ribosome binding domain, supporting the idea that GCN1 binds near the ribosomal acceptor site to promote GCN2 activation by uncharged tRNA [7].
• The mof4-1 strain is more sensitive to the aminoglycoside antibiotic paromomycin than a upf1 delta strain, and frameshifting efficiency increases in a mof4-1 strain grown in the presence of this drug [8].
• Chemical probing of mutant and wild-type ribosomes in the presence of paromomycin indicates that interactions between the antibiotic and 16S rRNA in mutant ribosomes are disrupted [9].
• We have injected cloned copies of the micronuclear rDNA that have been altered in vitro into developing macronuclei and obtained transformants that express the paromomycin-resistant phenotype specified by the injected rDNA [10].
• Molecular analysis of paromomycin-resistant embryogenic calli and of plants regenerated from these calli, confirmed the stable integration of bombarded DNA into the cassava genome [11].

Chemical compound and disease context of Neomycin E

• CASE REPORT: We report a case of cryptosporidial cholangitis in a patient with AIDS who responded to treatment with intravenous paromomycin followed by oral letrazuril as maintenance therapy [12].
• Epidemic visceral leishmaniasis in Sudan: a randomized trial of aminosidine plus sodium stibogluconate versus sodium stibogluconate alone [13].
• We report the characterization of an intrinsic, chromosomally carried aph(3')-IIc gene from Stenotrophomonas maltophilia clinical isolate K279a, encoding an aminoglycoside phosphotransferase enzyme that significantly increases MICs of kanamycin, neomycin, butirosin, and paromomycin when expressed in Escherichia coli [14].
• In the dexamethasone-treated rat model of cryptosporidiosis, paromomycin was effective at a dosage of 50 mg/kg/day or more for ileal infection and 200 mg/kg/day or more for cecal infection [15].
• Encouraged by in vitro results, we have assessed the in vivo activity of paromomycin (PRM) against Mycobacterium tuberculosis, multidrug-resistant (MDR) M. tuberculosis (resistant to isoniazid, rifampin, and streptomycin), and Mycobacterium avium complex in C57BL/6 mice and their beige counterparts [16].

Biological context of Neomycin E

• Conjugating cells of the ciliate Tetrahymena thermophila were electroporated in the presence of plasmid DNA containing a paromomycin-resistant ribosomal RNA gene (rDNA) [17].
• We constructed two circular plasmids carrying replication origin sequences from C3 rDNA and a point mutation (Pmr) in the 17S rRNA gene that confers resistance to the antibiotic paromomycin [18].
• A upf3-Delta strain demonstrates increased sensitivity to the antibiotic paromomycin and increased programmed -1 ribosomal frameshift efficiency resulting in loss of the M1 virus [19].
• Paromomycin bound at G332/G333 inhibited aminoacylation, and the inhibition was suppressed by the addition of SmpB, a tmRNA-binding protein [20].
• The nucleotide sequence of the 17S ribosomal RNA gene of Tetrahymena thermophila and the identification of point mutations resulting in resistance to the antibiotics paromomycin and hygromycin [21].

Anatomical context of Neomycin E

• The sensitivity to the aminoglycoside paromomycin has been analyzed in lymphoblastoid cell lines derived from five deaf individuals and five hearing individuals from an Arab-Israeli family carrying the A1555G mutation, and three married-in controls from the same family [22].
• The Saccharomyces cerevisiae temperature-sensitive (ts) allele nip7-1 exhibits phenotypes associated with defects in the translation apparatus, including hypersensitivity to paromomycin and accumulation of halfmer polysomes [23].
• Coadministration of erythromycin and, to a somewhat lesser degree, of paromomycin, markedly reduced the effects of amoscanate on the biliary tract [24].
• Identification of the paromomycin-resistance mutation in the 15 S rRNA gene of yeast mitochondria [25].
• We show here for the first time that the aminoglycosides G-418 and paromomycin have similar effects in monkey (COS-7) cells in vivo [26].

Associations of Neomycin E with other chemical compounds

• Overexpression of SIT4 leads to an elevation in resistance to paromomycin and to lesser extent tolerance to sorbic acid, but it has no detectable effect on resistance to 4-NQO [27].
• Indeed, succinate addition to paromomycin-treated cultures partly restored mitochondrial membrane potential [28].
• 5. With paromomycin or neomycin B and C as substrates, however, two pH values (5.5 and 9.0) for optimal activity were observed [29].
• A paromomycin and methylbenzethonium chloride ointment cured Leishmania enriettii infections in guinea pigs [30].
• Comparative efficacy evaluation of dicationic carbazole compounds, nitazoxanide, and paromomycin against Cryptosporidium parvum infections in a neonatal mouse model [31].

Gene context of Neomycin E

• Mutations in the MSS1 gene render the yeast cells respiratory deficient only in the presence of the PR454 mutation (paromomycin resistance) in the mitochondrial 15 S ribosomal RNA gene [32].
• However, disruption of NCL1 leads to increased sensitivity to the antibiotic paromomycin [33].
• Expression of the SSB1 gene from C. albicans, which codes for a member of the 70-kDa heat shock protein family, in S. cerevisiae ssb1 ssb2 double mutant complements the mutant phenotype (poor growth particularly at low temperature, and sensitivity to certain protein synthesis inhibitors, such as paromomycin) [34].
• Paromomycin and the prion [PSI+], which reduce translational fidelity, do not increase GCN4 expression to induce the suppression phenotype and in fact reduce derepression. eEF1A mutations that reduce translation, however, reduce expression of GCN4 under non-starvation conditions [35].
• MTO1 codes for a mitochondrial protein required for respiration in paromomycin-resistant mutants of Saccharomyces cerevisiae [36].

Analytical, diagnostic and therapeutic context of Neomycin E

• Measurements were repeated after treatment with paromomycin [37].
• Tetrahymena thermophila has been transformed to paromomycin-resistant phenotypes by microinjection of an aminoglycoside 3'-phosphotransferase (neo) gene under the control of the T. thermophila histone H4-I promoter [38].
• Isothermal titration calorimetry studies reveal that paromomycin binds to the EcWT duplex with a 31-fold higher affinity than the A1408G duplex, with this differential affinity being enthalpic in origin [39].
• Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been shown to be effective in in vitro and animal models against multiple-drug-resistant tuberculosis and the Mycobacterium avium complex [40].
• Chemoprophylaxis of Cryptosporidium parvum infection with paromomycin in kids and immunological study [41].

References