User talk:Fatin Hamd/sandbox

This article is very interesting and organized. Also, it has a good resources. fatin Alhawti--Fatin Hamd (talk) 21:31, 9 September 2018 (UTC)

23s rRNA Functions
In general, rRNA has an essential function of peptidyl transferase, the stimulating core of the ribosome plays role in the peptide bond configuration. Both peptidyl-tRNA and aminoacyl-tRNA are important for synthesizing protein and transpeptidation response. However, 23S rRNA positions which are G2252, A2451, U2506, and U2585 have a significant function for tRNA binding in P site of the large ribosomal subunit. These modification nucleotides in site P can inhibit peptidyl-tRNA from binding and  also remains U2555 modification intervene with transferring  peptidyl-tRNA to puromycin.Furthermore, the chemical modification of half of these positions G2251, G2253, A2439, and U2584 can not prevent the tRNA binding. Peptidyl-tRNA of 50s subunits which binds to the P site preserve eight positions of 23S rRNA from chemical modification. On the other hand, 23S rRNA impacts on mutation for cell growth. Mutations A1912G, A1919G and Ψ1917C have a powerful growth phenotypes and they prevent translation while mutation A1916G has a simple growth phenotype and it leads to defect in the 50S subunits. Fatin Alhawti--Fatin Hamd (talk) 03:05, 15 October 2018 (UTC)

Mutation in 23S rRNA and Linezolid relationship
A number of 23S rRNA mutations in the peptidyl transferase loop have given linear resistance in laboratory selection experiments in many organisms, and mutations based on the organism used, and mutations in both nucleotides directly in the linezolid link (positions 2061, 2451, and 2452 And 2504) and in nucleotides away from the binding pocket (positions 2032, 2062, 2447, 2453, 2499, 2500, 2576 and 2608). Thus, the G2576U mutation is most prevalent to the linezolid -resistant isolates. additionally, a number of other mutations in RSA 23S and L3 and L4 which are ribosomal protein were associated with linezolid resistance but with little evidence of the cause-and-effect relationship.

i-Single 23S rRNA mutations related with domain in the PTC region many antibiotics are particular to the ribosomes of one or two domains of life, in spite some of global antibiotics block ribosomes from all three domains. In fact, the clinical benefit of ribosomal antibiotics depend on their selection of bacterial ribosomes versus mammals. Linezolid is associated with peptidyl transferase of bacterial ribosomes but not to be less or much lower than eukaryotic cytosolic ribosomes. The linezolid predilection which is that the nucleotides in bacteria ribosome located out the ligament of the drug binding it is called second, third nucleotides and external nucleotide, affect their shapes and thus affect drug binding and susceptibility. The second layer nucleotide is 2453 and the third nucleotide 2032 and 2499 differ between human and bacteria cytosolic rRNA.

ii-Single and double 23S rRNA mutations areas relevant with antibiotic resistance Mutations at the 12 23S rRNA sites show that they confer linezolid resistance. The four sinale 23S rRNA nucleotides A2503G, G2505A, C2571G and C2612A which were associated with linezolid resistance without genetic evidence of resistance. The A2503G mutation was detected along with G2576U in S.aureus along with C2571G and A1743U in S.pneumoniae strains with decreased linezolid sensitivities. Furthermore, the A2503U mutation has associated with lower susceptibility to tiamulin, valnemulin, chloramphenicol, florfenicol and lincomycin in Mycoplasma galliswpticum. The mutation G2576U is the most significant 23S rRNA mutations detected in linezolid resistance clinical isolates. Single mutations of G2032A, C2055A, C2499A, U2504G and A2572U were either linked or shown to give linezolid antibiotic resistance or other PTC antibiotics to compare their effects with those mutations in M.smegmatis.In addition, double mutations of 23S rRNA related with antibiotic resistance, Some single mutations can not give resistant alone but they contribute to resistance with other mutant. G2032A-C2499A, G2032A-U2504G, C2055A-U2504G and C2055A-A2572U are combination of double mutation which have been observed in tiamulin resistant Brachyspira hyodysenteriae isolates. All of the double mutations exhibit a significant increase in MICs compared to the wild type and single mutant strains. Therefore, there are effected on linezolid resistance as double mutations give MICs higher linezolid than single mutation. The G2032A-U2504G an 8-fold shows increased in MIC linezolid related to U2504G single mutant. C2055A-U2504G shows a 4-fold increased in linezolid related to the single mutant U2504G. C2055A-A2572U mutation shows 16-fold increase in MIC linezolid related to single mutant A2572U. Also, there is effects on clindamycin resistance along with C2055A-A2572U mutation, where MIC is increased by 16 fold to 32 fold for wild type and C2055A and A2572 mutant. in addition, there is increase and decrease in MICs of chloramphenicol and valnemulin for double mutant related to their single mutants. Fatin Alhawti--Fatin Hamd (talk) 03:23, 15 October 2018 (UTC)