Antibiotic resistance is an escalating, worldwide problem. Due to excessive use of antibiotics, multidrug-resistant bacteria have become a serious threat and a major global healthcare problem of the 21st century. This fact creates an urgent need for new and effective antimicrobials. The common strategies for antibiotic discovery are based on either modifying existing antibiotics or screening compound libraries, but these strategies have not been successful in recent decades. An alternative approach could be to use gene-specific oligonucleotides, such as peptide nucleic acid (PNA) oligomers, that can specifically target any single pathogen. This approach broadens the range of potential targets to any gene with a known sequence in any bacterium, and could significantly reduce the time required to discover new antimicrobials or their redesign, if resistance arises. We review the potential of PNA as an antibacterial molecule. First, we describe the physicochemical properties of PNA and modifications of the PNA backbone and nucleobases. Second, we review the carriers used to transport PNA to bacterial cells. Furthermore, we discuss the PNA targets in antibacterial studies focusing on antisense PNA targeting bacterial mRNA and rRNA.

The identification of novel targets for antimicrobial agents is crucial for combating infectious diseases caused by evolving bacterial pathogens. Components of bacterial toxin–antitoxin (TA) systems have been recognized as promising therapeutic targets. These widespread genetic modules are usually composed of two genes that encode a toxic protein targeting an essential cellular process and an antitoxin that counteracts the activity of the toxin. Uncontrolled toxin expression may elicit a bactericidal effect, so they may be considered “intracellular molecular bombs” that can lead to elimination of their host cells. Based on the molecular nature of antitoxins and their mode of interaction with toxins, TA systems have been classified into six groups. The most prevalent are type II TA systems. Due to their ubiquity among clinical isolates of pathogenic bacteria and the essential processes targeted, they are promising candidates for the development of novel antimicrobial strategies. In this review, we describe the distribution of type II TA systems in clinically relevant human pathogens, examine how these systems could be developed as the targets for novel antibacterials, and discuss possible undesirable effects of such therapeutic intervention, such as the induction of persister cells, biofilm formation and toxicity to eukaryotic cells.

The study addresses the utilization of food waste by-products from faba bean (Vicia faba L.) pods (FBP) as an alternative feed supplement to promote sustainable piglet growth by reducing antimicrobial use. Objectives include evaluation of FBP in terms of nutritional components (proximate composition, fibres, minerals), phytochemical composition (total phenols, HPLC-MS profiling), and in vitro biological activities. Air-dried FBP from the cultivar ‘Bizon’ contained high levels of crude protein (144 g/kg), dietary fibre (413 g/kg), potassium (27.8 g/kg), and iron (126 mg/kg). Phytochemical analysis of methanolic extract from FBP revealed significant levels of polyphenols, including vestitol, piscidic acid, hydroxyeucomic acid, quercetin, and kaempferol glycosides with no detectable tannins. The extract showed negligible activity against porcine digestive enzymes (α-amylase, lipase, and trypsin) (IC₅₀ > 4 mg/mL) and demonstrated a dose-dependent antibacterial activity against Escherichia coli and Salmonella enterica in concentrations of 1–8 mg/mL. The extract had low cytotoxicity (IC₅₀ = 432.6 µg/mL) against IPEC-J2 – cells derived from porcine jejunal epithelium. The results indicate that FBP ‘Bizon’ is a valuable source of bioactive compounds with antibacterial properties, without adverse effects on porcine enzymes or IPEC-J2 cells, supporting its potential as a sustainable feed in piglet nutrition, in line with circular economy concepts.

Wound healing is a complex process in which TGFβ plays a key role. Previous studies have shown that syringin, a phenylpropanoid glycoside present in lilac bark (Syringa vulgaris L.), stimulates TGFβ expression in human monocyte-derived macrophages in addition to inhibiting the secretion of pro-inflammatory cytokines. Here, we investigated the effect of syringin on migration, invasion, and TGFβ production, as well as the effect on the release of pro-inflammatory cytokines in human dermal fibroblasts (NHDF) and keratinocytes (HaCaT) and its mechanism of action. NHDF and HaCaT cells were treated with the tested compound (12.5–100 µM), and a scratch assay was performed. The effect of migration using modified Boyden chambers was analyzed. TGFβ and IL-6 release were also assessed using ELISA kits. Cell proliferation was assessed using MTT and BrdU incorporation tests, while cytotoxicity was assessed using a neutral red uptake test. Smad2 and Smad3 phosphorylation were assessed using Western Blotting. ACTA2, COL1A1, and TIMP3 expression was analyzed using qPCR. Cells treated with syringin showed an increase in invasion potential in the scratch assay. A significant increase in skin fibroblast migration through the porous membrane was also observed. Syringin increased TGFβ release and inhibited IL-6 release by NHDF and HaCaT cells. No effect of syringin on cell proliferation or cytotoxic effects was observed. Western blot analysis showed significant activation of Smad2 and Smad3 in the presence of syringin in NHDF cells, but not in HaCaT. Quantitative PCR analysis revealed a strong increase in ACTA2 and COL1A1 gene expression in fibroblast cells treated with syringin. The present study demonstrated that syringin present in S. vulgaris stem bark increased dermal fibroblasts and keratinocytes’ wound healing function through activation of cell migration.

Bacterial populations can display different susceptibilities to antibiotics among individual cells, even though they originate from the same parent cell. This variability can lead to treatment failure and the emergence of resistant bacteria. Understanding the factors influencing this variability is crucial for developing effective antibiotic treatments. The underlying cause of variation in susceptibility distribution within bacterial populations remains unclear, necessitating the development of new tools for measurement. Here, we use a droplet microfluidic single-cell antibiotic susceptibility assay and focus on antibiotic resistance conveyed by the TEM β-lactamases family. We investigate how the catalytic activity of β-lactamase, and the genetic characteristics of the host strains affect the susceptibility distribution within bacterial populations at the single-cell level. For this purpose, we selected TEM-1 with the least catalytic activity against cefotaxime, followed by its two variants, R164S and G238S, exhibiting moderate and significant catalytic activity, respectively. The results showed that increasing the catalytic activity causes an increase in the population’s mean level of antibiotic resistance. While the type of β-lactamase influences the susceptibility distribution of the strains, this effect is independent of the catalytic activity of the strains. Besides, the genetic characteristics of the strains receiving the β-lactam resistance gene is an important factor that plays a role in the distribution of susceptibility.

Background/Objectives: Rheum officinale, an ethnomedicinal plant, has roots widely employed in modern pharmacological formulations. However, many of its biological activities remain only partly recognized. Furthermore, the metabolome and biological activity of its edible petioles, often considered a waste product, have received limited scientific attention. Methods and Results: The examination of anti-inflammatory properties of both root and petiole extracts (1–50 µg/mL) revealed the inhibition of the pro-inflammatory cytokine release from human peripheral blood mononuclear cells, a reduction in ALOX5 gene expression in human umbilical vein endothelial cells, and the significant inhibition (>60%) of cyclooxygenase-2 and 5-lipoxygenase activities. Importantly, no cytotoxic effects were detected at the tested concentrations. Conclusions: The petiole extract demonstrated anti-inflammatory efficiency comparable to, or exceeding that of the root extract, suggesting that R. officinale petioles could be valuable source of bioactive compounds for future investigations.