Mycobacterium tuberculosis epidemiology in Oman: whole-genome sequencing uncovers transmission pathways.

Tuberculosis (TB) originating from expatriates that hail from high TB-burden countries is hypothesized to play a role in continued TB transmission in Oman. Here, we used whole-genome sequencing (WGS) to assess national TB transmission dynamics. The annual incidence per 100,000 population per year was calculated for nationals and expatriates. A convenience sample of Mycobacterium tuberculosis (MTB) isolates from 2018 to 2019 was sequenced and analyzed with publicly available TB sequences from Bangladesh, Tanzania, the Philippines, India, and Pakistan. Relatedness was assessed by generating core-genome single nucleotide polymorphism (SNP) distances. The incidence of TB was five cases per 100,000 persons in 2018 and seven cases per 100,000 persons in 2020 (R2 = 0.34, P = 0.60). Incidence among nationals was 3.9 per 100,000 persons in 2018 and 3.5 per 100,000 persons in 2020 (R2 = 0.20, P = 0.70), and incidence among expatriates was 7.2 per 100,000 persons in 2018 and 12.7 per 100,000 persons in 2020 (R2 = 0.74, P = 0.34). Sixty-eight local MTB isolates were sequenced and analyzed with 393 global isolates. Isolates belonged to nine distinct spoligotypes. Two isolates, originating from an expatriate and an Omani national, were grouped into a WGS-based cluster (SNP distance < 12), which was corroborated by an epidemiological investigation. Relatedness of local and global isolates (SNP distance < 100) was also seen. The relatedness between MTB strains in Oman and those in expatriate countries of origin can aid inform TB control policy. Our results provide evidence that WGS can complement epidemiological analysis to achieve the End TB strategy goal in Oman. IMPORTANCE Tuberculosis (TB) incidence in Oman remains above national program control targets. TB transmission originating from expatriates from high TB-burden countries has been hypothesized to play a role. We used whole-genome sequencing (WGS) to assess TB transmission dynamics between expatriates and Omani nationals to inform TB control efforts. Available Mycobacterium tuberculosis isolates from 2018 to 2019 underwent WGS and analysis with publicly available TB sequences from Bangladesh, the Philippines, India, and Pakistan to assess for genetic relatedness. Our analysis revealed evidence of previously unrecognized transmission between an expatriate and an Omani national, which was corroborated by epidemiological investigation. Analysis of local and global isolates revealed evidence of distant relatedness between local and global isolates. Our results provide evidence that WGS can complement classic public health surveillance to inform targeted interventions to achieve the End TB strategy goal in Oman.

Experimental and Molecular Modeling Studies on the Complexation of Chromium(III) with the Angiotensin-Converting Enzyme Inhibitor Captopril.

Captopril (CPT) is an inhibitor of angiotensin I converting enzyme, used as a medication for the treatment of people with high blood pressure, renal insufficiency, and cardiovascular diseases. It inhibits the angiogenesis process, vasoconstriction, and tumor metastasis. Some metal-captopril complexes exhibit antimicrobial activities. In the current work, the formation of the CrIII-CPT complex was studied spectrophotometrically and potentiometrically in aqueous solution. Kinetics of CrIII-CPT complex formation was spectrophotometrically studied over the pH range 3.20-4.20, at an ionic strength of 0.3 M at 30-50 °C. CrIII-CPT complex formation was potentiometrically studied at 25 °C, where ligand protonation constants and complexes' overall stability constants were calculated. UV-vis absorption spectra were executed to confirm the complex formation. Density functional theory and molecular dynamics simulation were performed to search the geometries of the CrIII-CPT complex. Atoms in molecules and interaction region indicator calculations are used to investigate intermolecular interactions for the formation of CrIII-CPT complex. The antimicrobial activity of the CPT ligand and CrIII-CPT complex on the prevention and control of environmental pathogenic bacteria, as tested on both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli) via agar disc diffusion method, assess the ability to use as an antimicrobial agent. CPT had shown good antimicrobial activity against both types of bacteria, which had increased slightly the zone of inhibition in Cr-CPT that indicates the increased efficacy due to Cr(III) antimicrobial activity via its oxidative damage to the bacterial cell wall. No previous study tested the CPT antimicrobial activity against Gram-positive ones such as S. aureus.

New synthetic strategies for acyclic and cyclic pyrimidinethione nucleosides and their analogues.

Pyrimidinethione nucleosides are effective compounds and have significant and pivotal effects in several fields. New synthetic strategies for many pyrimidinethione nucleosides including acyclic and cyclic derivatives have been reported.

Pyrimidine non-nucleoside analogs: A direct synthesis of a novel class of N-substituted amino and N-sulfonamide derivatives of pyrimidines.

A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N'-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N'-(2-cyanoacetyl)arylsulfonohydrazides. The scope and limitation of the method are demonstrated. The antibacterial and antifungal activities of the synthesized compounds were also evaluated.

Nucleic acid components and their analogs: Design and synthesis of novel cytosine thioglycoside analogs.

The synthesis of a new category of novel cytosine 4-thioglycoside analogs has been first accomplished. The main step of this strategy is the synthesis of sodium pyrimidine-4-thiolate through the condensation of 2-cyano-N-arylacetamides with sodium cyanocarbonimidodithioate, followed by coupling with α-bromo-sugars to afford the corresponding cytosine 4-thioglycoside analogs. The free thioglycosides were also prepared. Subsequent studies on the application of this strategy for the preparation of other potent pyrimidine thioglycosides are reported.

Crystal structure of (E)-2-amino-4-methyl-sulfanyl-6-oxo-1-{[(thiophen-2-yl)-methyl-idene]-amino}-1,6-di-hydro-pyrimidine-5-carbo-nitrile.

The title compound, C11H9N5OS2, a 1-thio-phen-2-yl-methyl-ene-amino-pyrimidine derivative, displays an essentially planar C-NH2 group. The conformation across the N=C bond linking the pyrimidine and thienyl groups is E. The pyrimidine and thienyl ring systems subtend an inter-planar angle of 42.72 (5)°. In the crystal, mol-ecules are linked by N-H⋯Nnitrile and N-H⋯O=C hydrogen bonds, forming chains parallel to the b axis.

Crystal structure of N-(2-amino-5-cyano-4-methyl-sulfanyl-6-oxo-1,6-dihydropyrimidin-1-yl)-4-bromo-benzene-sulfonamide di-methyl-formamide monosolvate.

The title compound, C12H10BrN5O3S2·C3H7NO, displays an almost planar amine group. The inter-planar angle between the rings is 31.72 (6)°. The residues are associated into ribbons parallel to [110] by three classical hydrogen bonds; one from each amine Hamine to ODMF and one from NHamide to Ooxo. Adjacent ribbons are connected by translation parallel to the c axis by a 'weak' hydrogen bond Hmeth-yl⋯Osulfon-yl to form a layer structure parallel to (1-10), while a further contact Hbromo-phen-yl⋯Osulfon-yl connects the residues in the third dimension.