Bacterial Succinoglycans: Structure, Physical Properties, and Applications

Succinoglycan is a type of bacterial anionic exopolysaccharide produced from Rhizobium, Agrobacterium, and other soil bacteria. The exact structure of succinoglycan depends in part on the type of bacterial strain, and the final production yield also depends on the medium composition, culture conditions, and genotype of each strain. Various bacterial polysaccharides, such as cellulose, xanthan, gellan, and pullulan, that can be mass-produced for biotechnology are being actively studied. However, in the case of succinoglycan, a bacterial polysaccharide, relatively few reports on production strains or chemical and structural characteristics have been published. Physical properties of succinoglycan, a non-Newtonian and shear thinning fluid, have been reported according to the ratio of substituents (pyruvyl, succinyl, acetyl group), molecular weight (Mw), and measurement conditions (concentration, temperature, pH, metal ion, etc.). Due to its unique rheological properties, succinoglycan has been mainly used as a thickener and emulsifier in the cosmetic and food industries. However, in recent reports, succinoglycan and its derivatives have been used as functional biomaterials, e.g., in stimuli-responsive drug delivery systems, therapeutics, and cell culture scaffolds. This suggests a new and expanded application of succinoglycan as promising biomaterials in biomedical fields, such as tissue engineering, regenerative medicine, and pharmaceuticals using drug delivery.

Umpolung of Indoles: Triflic Acid-Mediated C3-Regioselective Hy-droarylation of N-H Indoles

The direct dearomative addition of arenes to the C3-position of unprotected indoles is reported under operationally simple conditions with triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to gen-erate an electrophilic indole at the C3-position without the need to introduce a deactivating acetyl group on the indolic nitrogen as in previously reported strategies. This atom economy method delivers biologically relevant 3-aryl indolines and 3,3-spiroindolines in high yields and regioselectivities from both intra and intermolecular processes.

Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility

Resistance to amikacin in Gram-negatives is usually mediated by the 6'-N-acetyltransferase type Ib [AAC(6')-Ib], which catalyzes the transfer of an acetyl group from acetyl CoA to the 6' position of the antibiotic molecule. A path to continue the effective use of amikacin against resistant infections is to combine it with inhibitors of the inactivating reaction. We have recently observed that addition of Zn2+ to in-vitro enzymatic reactions, obliterates acetylation of the acceptor antibiotic. Furthermore, when added to amikacin-containing culture medium in complex to ionophores such as pyrithione (ZnPT), it prevents the growth of resistant strains. An undesired property of ZnPT is its poor water-solubility, a problem that currently affects a large percentage of newly designed drugs. Water-solubility helps drugs to dissolve in body fluids and be transported to the target location. We tested a pyrithione derivative described previously (Magda et al. Cancer Res 68:5318–5325, 2008) that contains the amphoteric group di(ethyleneglycol)-methyl ether at position 5 (compound 5002), a modification that enhances the solubility. Compound 5002 in complex with zinc (Zn5002) was tested to assess growth inhibition of amikacin-resistant Acinetobacter baumannii and Klebsiella pneumoniae strains in the presence of the antibiotic. Zn5002 complexes in combination with amikacin at different concentrations completely inhibited growth of the tested strains. However, the concentrations needed to achieve growth inhibition were higher than those required to achieve the same results using ZnPT. Time-kill assays showed that the effect of the combination amikacin/Zn5002 was bactericidal. These results indicate that derivatives of pyrithione with enhanced water-solubility, a property that would make them drugs with better bioavailability and absorption, are a viable option for designing inhibitors of the resistance to amikacin mediated by AAC(6')-Ib, an enzyme commonly found in the clinics.

Semi-Manual Processing Of Blood Clamps Waste into Chitosan Powder

Blood clams (Anadara granosa) are endemic clams found in Southeast Asia and East Asia. Blood clams are widely consumed by the public as seafood dishes in coastal food stalls. The great potential of blood clams will increase the waste of clam shells produced. The accumulation of shellfish waste will cause pollution and reduce environmental aesthetics. The chitin content in blood clam shells can be used as chitosan. Chitosan is a polymer of -(1-4) glucosamine which is formed when the acetyl group in chitin is substituted by hydrogen to become an amine group. Chitosan has antibacterial and antifungal properties. Isolation of chitosan was carried out through the stages of demineralization, deproteination, and deacetylation. The limited use of laboratories during the pandemic is a major obstacle in the isolation process of chitosan. This study aims to process blood clam shell waste into chitosan in a simple way on a home scale. Processing includes deproteination, demineralization, and deacetylation were done using tools and materials available at home. Laboratory equipment such as beakers could be replaced with pots, the reflux process was replaced by using a cloth to filter, and measuring cups were replaced with glasses. The research used 1500 grams of blood clam shell powder and produced 1050 grams of white chitosan with a slightly hard texture

Acetylation of glucosyltransferases regulates Streptococcus mutans biofilm formation and virulence

Lysine acetylation is a frequently occurring post-translational modification (PTM), emerging as an important metabolic regulatory mechanism in prokaryotes. This process is achieved enzymatically by the protein acetyltransferase (KAT) to specifically transfer the acetyl group, or non-enzymatically by direct intermediates (acetyl phosphate or acetyl-CoA). Although lysine acetylation modification of glucosyltransferases (Gtfs), the important virulence factor in Streptococcus mutans, was reported in our previous study, the KAT has not been identified. Here, we believe that the KAT ActG can acetylate Gtfs in the enzymatic mechanism. By overexpressing 15 KATs in S. mutans, the synthesized water-insoluble extracellular polysaccharides (EPS) and biofilm biomass were measured, and KAT (actG) was identified. The in-frame deletion mutant of actG was constructed to validate the function of actG. The results showed that actG could negatively regulate the water-insoluble EPS synthesis and biofilm formation. We used mass spectrometry (MS) to identify GtfB and GtfC as the possible substrates of ActG. This was also demonstrated by in vitro acetylation assays, indicating that ActG could increase the acetylation levels of GtfB and GtfC enzymatically and decrease their activities. We further found that the expression level of actG in part explained the virulence differences in clinically isolated strains. Moreover, overexpression of actG in S. mutans attenuated its cariogenicity in the rat caries model. Taken together, our study demonstrated that the KAT ActG could induce the acetylation of GtfB and GtfC enzymatically in S. mutans, providing insights into the function of lysine acetylation in bacterial virulence and pathogenicity.

Improving Hydrophobicity of Tropical Hardwood along Axial Positions

Wood is hygroscopic and is considered dimensionally unstable materials when exposed to wet conditions. To increase the hydrophobicity of wood, this study focused on the modification of tropical hardwood (Triplochiton scleroxylon) along different positions of the stem using acetic anhydride The weight percent gain (WPG) was determined and acetylation reaction was confirmed with FTIR. The dimensional stability of the wood was characterized by water absorption (WA), volumetric swelling (VS), anti-swelling efficiency (ASE), and water repellent efficiency (WRE). Data obtained were subjected to analysis of variance at α0.05. It was observed that the weight gain (WG) by acetylation increases along the axial position (base to top) of T. scleroxylon wood. IR-spectra confirmed properly the substitution of the acetyl group. The treatment resulted in a marked improvement in the WA and VS, ASE, and WRE of acetylated T. scleroxylon wood were also found to improve considerably from base to top of the wood. It could be said that the WPG and hydrophobicity increased, but the percentage of water absorption and volumetric swelling diminished. Hence, the modified wood showed good hydrophobicity and improved dimensional stability.

An essential ER-resident N-acetyltransferase in Plasmodium falciparum

N-terminal acetylation is a common eukaryotic protein modification that involves the addition of an acetyl group to the N-terminus of a polypeptide. This modification is largely performed by cytosolic N-terminal acetyltransferases (NATs). Most associate with the ribosome, acetylating nascent polypeptides co-translationally. In the malaria parasite Plasmodium falciparum, exported effectors are translated into the ER, processed by the aspartic protease plasmepsin V and then N-acetylated, despite having no clear access to cytosolic NATs. Here, we used post-transcriptional knockdown to investigate the most obvious candidate, Pf3D7_1437000. We found that it co-localizes with the ER-resident plasmepsin V and is required for parasite growth. However, depletion of Pf3D7_1437000 had no effect on protein export or acetylation of the exported proteins HRP2 and HRP3. Pf3D7_1437000-depleted parasites arrested later in their development cycle than export-blocked parasites, suggesting the protein's essential role is distinct from protein export.

Green Synthesis of New Pyrrolo [1,2-a] quinoxalines as Antiproliferative Agents in GPER-expressing Breast Cancer Cells

4,5-Dihydropyrrolo [1,2-a]quinoxalines are interesting druggable scaffolds, with multifaceted biological properties, including anticancer properties targeting the G protein-coupled estrogen receptor 1 (GPER). In this work, the synthesis and preliminary antiproliferative activity of a small set of new 4,5-dihydropyrrolo[1,2-a]quinoxalines (18-20) and pyrrolo[1,2-a]quinoxalines (21, 22) has been reported, inspired by known antiproliferative agents (G-1, G-15, and G-36). The synthesis of the pyrroloquinoxalinic core was employed following the Pictet–Spengler reaction, using the surfactant p-dodecylbenzene sulphonic acid (p-DBSA), as catalyst. It demonstrated efficiency in the catalysis of the 4-phenylpyrrole [1,2-a] quinoxaline type compound formation in mild solvents such as water, ethanol, and hydroalcoholic solutions. In addition, the reactions proceeded in a short time (between 15 and 120 minutes) at room temperature and with high yields. The in vitro MTT assays showed that the presence of isopropyl groups furnished promising antiproliferative compounds. Although, the acetyl group provided also antiproliferative effects, breaking down its responsibility in the GPER transactivation. Nevertheless, it is possible to conclude that the 4,5-dihydropyrrolo[1,2-a]quinoxalines remain a feasible scaffold to develop anticancer agents against GPER-expressing cells.

Sirtuins as Interesting Players in the Course of HIV Infection and Comorbidities

The sirtuins (SIRTs) are a family of enzymes from the group of NAD+-dependent deacetylases. Through the reaction of splitting the acetyl group of various transcription factors and histones they regulate many processes in the organism. The activity of sirtuins is linked to metabolic control, oxidative stress, inflammation and apoptosis, and they also affect the course of viral infections. For this reason, they may participate in the pathogenesis and development of many diseases, but little is known about their role in the course of human immunodeficiency virus (HIV) infection, which is the subject of this review. In the course of HIV infection, comorbidities such as: neurodegenerative disorders, obesity, insulin resistance and diabetes, lipid disorders and cardiovascular diseases, renal and bone diseases developed more frequently and faster compared to the general population. The role of sirtuins in the development of accompanying diseases in the course of HIV infection may also be interesting. There is still a lack of detailed information on this subject. The role of sirtuins, especially SIRT1, SIRT3, SIRT6, are indicated to be of great importance in the course of HIV infection and the development of the abovementioned comorbidities.