Increasing multidrug resistance has led to renewed interest in phage-based therapy. A combination of the bacteriophages and antibiotics presents a promising approach enhancing the phage therapy effectiveness. First, phage candidates for therapy should be deeply characterized. Here we characterize the bacteriophage vB_AbaP_AGC01 that poses antibacterial activity against clinical Acinetobacter baumannii strains. Moreover, besides genomic and phenotypic analysis our study aims to analyze phage–antibiotic combination effectiveness with the use of ex vivo and in vivo models. The phage AGC01 efficiently adsorbs to A. baumannii cells and possesses a bacteriolytic lifecycle resulting in high production of progeny phages (317 ± 20 PFU × cell−1). The broad host range (50.27%, 93 out of 185 strains) against A. baumannii isolates and the inability of AGC01 to infect other bacterial species show its high specificity. Genomic analysis revealed a high similarity of the AGC01 genome sequence with that of the Friunavirus genus from a subfamily of Autographivirinae. The AGC01 is able to significantly reduce the A. baumannii cell count in a human heat-inactivated plasma blood model (HIP-B), both alone and in combination with antibiotics (gentamicin (GEN), ciprofloxacin (CIP), and meropenem (MER)). The synergistic action was observed when a combination of phage treatment with CIP or MER was used. The antimicrobial activity of AGC01 and phage-antibiotic combinations was confirmed using an in vivo larva model. This study shows the greatest increase in survival of G. mellonella larvae when the combination of phage (MOI = 1) and MER was used, which increased larval survival from 35% to 77%. Hence, AGC01 represents a novel candidate for phage therapy. Additionally, our study suggests that phages and antibiotics can act synergistically for greater antimicrobial effect when used as combination therapy.
In the post-antibiotic era the issue of bacterial resistance refers not only to antibiotics themselves but also to common antiseptics like octenidine dihydrochloride (OCT). This appears as an emerging challenge in terms of preventing staphylococcal infections, which are both potentially severe and easy to transfer horizontally. Essential oils have shown synergisms both with antibiotics and antiseptics. Therefore the aim of this study was to investigate the impact of lavender essential oil (LEO) on OCT efficiency towards methicillin-resistant S. aureus strains (MRSA). The LEO analyzed in this study increased the OCT’s susceptibility against MRSA strains. Subsequent FTIR analysis revealed cellular wall modifications in MRSA strain cultured in media supplemented with OCT or LEO/OCT. In conclusion, LEO appears to be a promising candidate for an efficient enhancer of conventional antiseptics.
Transforming growth factor-β (TGF-β) is a key protein family member that includes activins, inhibins, and bone morphogenetic proteins (BMPs). It is essential in numerous biological processes, such as chemotaxis, apoptosis, differentiation, growth, and cell migration. TGF-β receptors initiate signaling through two primary pathways: the canonical pathway involving Smad proteins and non-canonical pathways that utilize alternative signaling mechanisms. When TGF-β signaling is disrupted, it has been shown to contribute to the development of various diseases, including cancer. Initially, TGF-β effectively inhibits the cell cycle and promotes apoptosis. However, its role can transition to facilitating tumor growth and metastasis as the disease progresses. Moreover, TGF-β drives cancer progression through epithelial–mesenchymal transition (EMT), modulation of factor expression, and evasion of immune responses. This complexity establishes the need for further research, particularly into pharmacological agents targeting TGF-β, which are emerging as promising therapeutic options. Current clinical and preclinical studies are making significant strides toward mitigating the adverse effects of TGF-β. This underscores the critical importance of understanding its underlying mechanisms to enhance treatment effectiveness and improve survival rates for cancer patients.
The human microbiome has been proven to contribute to the human condition, both in health and in disease. The metagenomic approach based on next-generation sequencing has challenged the dogma of urine sterility. The human urobiome consists of bacteria and eukaryotic viruses as well as bacteriophages, which potentially represent the key factor. There have been several significant findings with respect to the urobiome in the context of urological disorders. Still, the research on the urobiome in chronic kidney disease and kidney transplantation remains underrepresented, as does research on the role of the virome in the urinary microbiota. In this review, we present recent findings on the urobiome with a particular emphasis on chronic kidney disease and post-kidney transplantation status. Challenges and opportunities arising from the research on the human urobiome will also be discussed.
Because of the bacterial drug resistance development, it is reasonable to investigate chemical compounds capable of preventing the spread of resistance to mupirocin (MUP), commonly used in staphylococcal eradication. The objective of the study was to verify the influence of essential oil compounds (EOCs) on the antibacterial activity of MUP against mupirocin-susceptible (MupS) and induced low-level mupirocin-resistant (MupRL) methicillin-resistant Staphylococcus aureus (MRSA) strains. The following parameters were examined: MRSAMupS and MRSAMupRL susceptibility to EOCs (1,8-cineole, eugenol, carvacrol, linalool, (-)-menthone, linalyl acetate, and trans-anethole), the bacterial cell size distribution, and chemical composition by the use of Fourier Transform Infrared Spectroscopy (FTIR) and Raman spectroscopies. The MRSAMupS and MRSAMupRL strains were susceptible to all tested EOCs. 1,8-cineole and (-)-menthone showed synergistic activity against MRSAMupS in combination with mupirocin, whereas 1,8-cineole exhibited synergistic activity against MRSAMupRL as well. In-depth analysis showed that both MRSAMupS and MRSAMupRL displayed similar distributions of the bacterial cell size. The FTIR and Raman spectra of the MRSAMupS and MRSAMupRL strains showed differences in some regions. New bands in the MRSAMupRL Raman spectrum were observed. It was concluded that the use of 1,8-cineole in combination with mupirocin can increase the mupirocin activity against the MRSAMupS and MRSAMupRL strains.
The study aimed to analyze morphological and functional changes of Staphylococcus aureus cells due to trans-anethole (a terpenoid and the major constituent of fennel, anise, or star anise essential oils) exposition, and their consequences for human neutrophils phagocytic activity as well as IL-8 production (recognized as the major chemoattractant). The investigation included the evaluation of changes occurring in S. aureus cultures, i.e., staphyloxanthin production, antioxidant activities, cell size distribution, and cells composition as a result of incubation with trans-anethole. It was found that the presence of trans-anethole in the culture medium reduced the level of staphyloxanthin production, as well as decreased antioxidant activities. Furthermore, trans-anethole-treated cells were characterized by larger size and a tendency to diffuse in comparison to the non-treated cells. Several cell components, such as phospholipids and peptidoglycan, were found remarkably elevated in the cultures treated with trans-anethole. As a result of the aforementioned cellular changes, the bacteria were phagocytized by neutrophils more efficiently (ingestion and parameters associated with killing activity were at a higher level as compared to the control system). Additionally, IL-8 production was at a higher level for trans-anethole modified bacteria. Our results suggest that trans-anethole represents a promising measure in combating severe staphylococcal infections, which has an important translational potential for clinical applications.