Second-Generation Meridianin Analogues Inhibit the Formation of Mycobacterium smegmatis Biofilms and Sensitize Polymyxin-Resistant Gram-Negative Bacteria to Colistin

Drug-resistant bacteria are rapidly becoming a significant problem across the globe. One element that factors into this crisis is the role played by bacterial biofilms in the recalcitrance of some infections to the effects of conventional antibiotics. Bacteria within a biofilm are highly tolerant of both antibiotic treatment and host immune responses. Biofilms are implicated in many chronic infections, including tuberculosis, in which they can act as bacterial reservoirs, requiring an arduous antibiotic regimen to eradicate the infection. A separate, compounding problem is that antibiotics once seen as last-resort drugs, such as the polymyxin colistin, are now seeing more frequent usage as resistance to front-line drugs in Gram-negative bacteria becomes more prevalent. The increased use of such antibiotics inevitably leads to an increased frequency of resistance. Drugs that inhibit biofilms and/or act as adjuvants to overcome resistance to existing antibiotics will potentially be an important component of future approaches to antibacterial treatment. We have previously demonstrated that analogues of the meridianin natural product family possess adjuvant and antibiofilm activities. In this study, we explore structural variation of the lead molecule from previous studies, and identify compounds showing both improved biofilm inhibition potency and synergy with colistin.     

化香果提取物体外抑菌活性研究

研究了化香果提取物对水产常见9种致病菌嗜水气单胞菌（Aeromonas hydrophila）、温和气单胞菌（Aeromonas sobria）、豚鼠气单胞菌（Aeromonas caviae）、维氏气单胞菌（Aeromonas veronii）、迟钝爱德华菌（Edwardsiella tarda）、副溶血弧菌（Vibrio parahaemolyticus）、鼠疫耶尔森氏菌（Yersinia pestis）、大肠杆菌（Escherichia coli）和金黄色葡萄球菌（Staphylococcus aureus）的抑菌活性。研究结果表明：化香果提取物对9种细菌均具有抑制作用，最小抑菌浓度为4.50 g/L。对每种细菌而言，抑菌效果随化香果提取物质量浓度的增加而增强，其中对大肠杆菌的抑制能力最强，IC₅₀值为0.035 g/L；金黄色葡萄球菌次之，IC₅₀值为0.053 g/L。对雌雄小鼠急性经口毒性试验结果表明化香果提取物对小鼠的急性经口半数致死量（LD₅₀值）分别为5 010和7 940 mg/kg体质量，表明化香果提取物属于实际无毒级。     

Impact of an Engineered Copper-Titanium Dioxide Nanocomposite and Parent Substrates on the Bacteria Viability,Antioxidant Enzymes and Fatty Acid Profiling

Due to the systematic increase in the production of nanomaterials (NMs) and their applications in many areas of life, issues associated with their toxicity are inevitable. In particular, the performance of heterogeneous NMs, such as nanocomposites (NCs), is unpredictable as they may inherit the properties of their individual components. Therefore, the purpose of this work was to assess the biological activity of newly synthesized Cu/TiO₂-NC and the parent nanoparticle substrates Cu-NPs and TiO₂-NPs on the bacterial viability, antioxidant potential and fatty acid composition of the reference Escherichia coli and Bacillus subtilis strains. Based on the toxicological parameters, it was found that B. subtilis was more sensitive to NMs than E. coli. Furthermore, Cu/TiO₂-NC and Cu-NPs had an opposite effect on both strains, while TiO₂-NPs had a comparable mode of action. Simultaneously, the tested strains exhibited varied responses of the antioxidant enzymes after exposure to the NMs, with Cu-NPs having the strongest impact on their activity. The most considerable alternations in the fatty acid profiles were found after the bacteria were exposed to Cu/TiO₂-NC and Cu-NPs. Microscopic images indicated distinct interactions of the NMs with the bacterial outer layers, especially in regard to B. subtilis. Cu/TiO₂-NC generally proved to have less distinctive antimicrobial properties on B. subtilis than E. coli compared to its parent components. Presumably, the biocidal effects of the tested NMs can be attributed to the induction of oxidative stress, the release of metal ions and specific electrochemical interactions with the bacterial cells.     

A new insight into the adsorption mechanism of patulin by the heat-inactive lactic acid bacteria cells

The primary objective of this study was to identify the characteristics of the heat-inactived lactic acid bacteria (LAB) cells involved in the adsorption of patulin. The bacterial cells were characterized by Scanning Electron Microscopy coupled with Energy Dispersive X-Ray Spectroscopy (SEM-EDS), Transmission Electron Microscopy (TEM) and Brunauer–Emmett–Teller (BET) technique. The patulin-exposed bacterial cells and patulin-unexposed bacterial cells were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Zeta Potential and Contact Angle Method. It was found that Lactobacillus brevis 20023 (LB-20023), which has the highest specific surface area and cell wall volume, showed the highest capacity to adsorb patulin from the aqueous solution. Five major elements (C, N, O, P, and S) were detected by SEM-EDS, and LB-20023 displayed the highest nitrogen-to-carbon (N/C) ratio (0.2938). LB-20023 exhibited the highest hydrophobicity, but the zeta potential was not prominent compared to other bacterial cells. The main functional groups involved in adsorbing patulin were C–O, OH and/or NH groups, suggesting that polysaccharides and/or protein were important functional components. Above all, the adsorption capacity of bacterial cells had close relationships with physical and chemical properties of cell surface, including specific surface area, cell wall volume, nitrogen-to-carbon (N/C) ratio, hydrophobicity and functional groups. Further study will be needed to find other additional functional factors.     

Expression of Main Toll-Like Receptors in Patients with Different Types of Colorectal Polyps and Their Relationship with Gut Microbiota

Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman’s correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.