An actinomycete strain #8 with multiple aminoglycoside (AG) resistance and paromomycin (PRM) sensitivity was examined for its capability of enzymatic modification of AGs. Cell free extracts from the strain converted all of the examined AGs including PRM in the presence of acetyl CoA. PRM was completely modified to at least two products (major and minor spots upon TLC) without significant reduct...

Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients wi...

Background. Post-kala-azar dermal leishmaniasis (PKDL) plays an important role in maintaining endemicity of visceral leishmaniasis and its transmission. Treatment regimens for PKDL are toxic and require 3-4 months of hospitalization. These long and arduous regimens result in extensive noncompliance. There is an urgent need to develop a safe, effective, and acceptable regimen for the treatment o...

Pentavalent antimonials (SbV) have been successfully used for treatment of kala-azar since last six decades. Since 1970s its conventional dosages have failed to achieve with 60 per cent unresponsiveness reported with WHO regimen in Bihar (India). Pentamidine initially used as a second line of drug, acquired resistance (25%) even with prolonged dosage. Newer oral drug miltefosine is a potent ant...

Inferring antibiotic mechanisms on translation through static structures has been challenging, as biological systems are highly dynamic. Dynamic single-molecule methods are also limited to few simultaneously measurable parameters. We have circumvented these limitations with a multifaceted approach to investigate three structurally distinct aminoglycosides that bind to the aminoacyl-transfer RNA...

The new guanidinylation reagent N,N'-diBoc-N''-triflylguanidine was used to efficiently convert multiamine-containing glycosides including kanamycin A and B, tobramycin, paromomycin, and neomycin B to the corresponding fully guanidinylated analogues (guanidinoglycosides). This transformation occurs in the presence of H(2)O under mild conditions. Guanidinotobramycin and guanidinoneomycin B were ...

Three genotypically suppressible alleles, a1X4, alcA125, and niaD500, are phenotypically suppressed by aminoglycoside antibiotics. Unsuppressible alleles at these loci are unaffected as are known missense mutations at the yA and gdhA loci. This is consistent with the premise that the suppressible mutations are nonsense and that this highly-allele-specific phenotypic suppression can be used to d...

A successful approach to deliver paromomycin, a poorly absorbed aminoglycoside antibiotic, to parasite cells is reported, based on selective protection of amino and hydroxyl groups followed by conjugation to a fluorolabeled, PEG-functionalized cell-penetrating Tat(48-60) peptide. The resulting construct is efficiently internalized into Leishmania cells, evidencing the fitness of cell-penetratin...

Nghiên cứu được thực hiện nhằm cải thiện độ nhạy của cảm biến sinh học nhận diện nhóm kháng ức chế sự tổng hợp protein trên nền giấy. Cảm dựa cường phát quang nanoluciferase (NanoLuc) giấy đông khô có chứa hệ thống phiên mã dịch trong điều kiện phòng thí nghiệm. Khi nhỏ nước lên giấy, NanoLuc và sáng khi kết với cơ chất Furimazine. Ngược lại, vi khuẩn, bị cản trở dẫn đến yếu. Cường ghi bằng máy...