Combined Use of Antimicrobial Peptides with Antiseptics against Multidrug-Resistant Bacteria: Pros and Cons.

Antimicrobial peptides (AMPs) are acknowledged as a promising template for designing new antimicrobials. At the same time, existing toxicity issues and limitations in their pharmacokinetics make topical application one of the less complicated routes to put AMPs-based therapeutics into actual medical practice. Antiseptics are one of the common components for topical treatment potent against antibiotic-resistant pathogens but often with toxicity limitations of their own. Thus, the interaction of AMPs and antiseptics is an interesting topic that is also less explored than combined action of AMPs and antibiotics. Herein, we analyzed antibacterial, antibiofilm, and cytotoxic activity of combinations of both membranolytic and non-membranolytic AMPs with a number of antiseptic agents. Fractional concentration indices were used as a measure of possible effective concentration reduction achievable due to combined application. Cases of both synergistic and antagonistic interaction with certain antiseptics and surfactants were identified, and trends in the occurrence of these types of interaction were discussed. The data may be of use for AMP-based drug development and suggest that the topic requires further attention for successfully integrating AMPs-based products in the context of complex treatment. AMP/antiseptic combinations show promise for creating topical formulations with improved activity, lowered toxicity, and, presumably, decreased chances of inducing bacterial resistance. However, careful assessment is required to avoid AMP neutralization by certain antiseptic classes in either complex drug design or AMP application alongside other therapeutics/care products.

Hemolytic Activity, Cytotoxicity, and Antimicrobial Effects of Silver Nanoparticles Conjugated with Lincomycin or Cefazolin.

The overuse of antibiotics has led to the emergence of resistant bacteria. A good alternative is silver nanoparticles, which have antibacterial activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant strains. Their combination with already known antibiotics has a synergistic effect. In this work, we studied the synthesis of conjugates of silver nanoparticles with two antibiotics, lincomycin and cefazolin. Albumin and glutathione were used as spacer shells with functional groups. The physicochemical properties of the obtained conjugates, their cytotoxicity and synergism of antimicrobial activity were studied. The 50% antimicrobial activity of the obtained samples was shown, which allows them to be recommended for use as topical drug preparations.

Incidence of Common Herpesviruses in Colonic Mucosal Biopsies Following Hematopoietic Stem Cell Transplantation.

Intestinal complications are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, only scarce data concern herpesvirus incidence in the colonic mucosa post-HSCT. Our purpose was to assess the frequency and clinical significance of cytomegalovirus (CMV), Epstein−Barr virus (EBV), human herpesvirus type 6 (HHV6), and herpes simplex virus (HSV) in the colonic mucosa post-HSCT. The study group included 119 patients of different ages, mostly with leukemias and lymphomas, subjected to allo-HSCT from haploidentical related (48%) or HLA-compatible donors (52%). In total, 155 forceps biopsies of the colonic mucosa were taken in cases of severe therapy-resistant intestinal syndrome post-HSCT. Most samples were taken from the descending, sigmoid, and transverse colon. Intestinal GVHD or local infections were assessed clinically and by histology. EBV, CMV, HSV, and HHV6 were tested in colonic mucosal lysates with commercial PCR assays. HSV was found in <8% of colonic samples, along with high HHV6 and CMV positivity (up to 62% and 35%, respectively) and a higher EBV incidence at 5−6 months post-HSCT (35%). For CMV and EBV, significant correlations were revealed between their rates of detection in blood and colonic mucosa (r = 0.489 and r = 0.583; p < 0.05). No significant relationships were found between the presence of herpesviruses and most patients' characteristics. EBV positivity in colonic samples was correlated with delayed leukocyte and platelet recovery post-HSCT. Higher EBV frequency in the colonic mucosa was found in deceased patients (56% versus 21%, p = 0.02). The correlations among EBV positivity in the colon, lethality rates and delayed hematopoietic reconstitution suggest some relationship with systemic and local EBV reactivation post-transplant.

Hemolytic Activity, Cytotoxicity, and Antimicrobial Effects of Human Albumin- and Polysorbate-80-Coated Silver Nanoparticles.

In this study, we aimed to develop a technique for colloidal silver nanoparticle (AgNP) modification in order to increase their stability in aqueous suspensions. For this purpose, 40-nm spherical AgNPs were modified by the addition of either human albumin or Tween-80 (Polysorbate-80). After detailed characterization of their physicochemical properties, the hemolytic activity of the nonmodified and modified AgNPs was investigated, as well as their cytotoxicity and antimicrobial effects. Both albumin- and Tween-80-coated AgNPs demonstrated excellent stability in 0.9% sodium chloride solution (>12 months) compared to nonmodified AgNPs, characterized by their rapid precipitation. Hemolytic activity of nonmodified and albumin-coated AgNPs was found to be minimal, while Tween-80-modified AgNPs produced significant hemolysis after 1, 2, and 24 h of incubation. In addition, both native and Tween-80-covered AgNPs showed dose-dependent cytotoxic effects on human adipose-tissue-derived mesenchymal stem cells. The albumin-coated AgNPs showed minimal cytotoxicity. The antimicrobial effects of native and albumin-coated AgNPs against S. aureus, K. pneumonia, P. aeruginosa, Corynebacterium spp., and Acinetobacter spp. were statistically significant. We conclude that albumin coating of AgNPs significantly contributes to improve stability, reduce cytotoxicity, and confers potent antimicrobial action.

Pattern of circulating SARS-CoV-2-specific antibody-secreting and memory B-cell generation in patients with acute COVID-19.

OBJECTIVES: To predict the spread of coronavirus disease (COVID-19), information regarding the immunological memory for disease-specific antigens is necessary. The possibility of reinfection, as well as the efficacy of vaccines for COVID-19 that are currently under development, will largely depend on the quality and longevity of immunological memory in patients. To elucidate the process of humoral immunity development, we analysed the generation of plasmablasts and virus receptor-binding domain (RBD)-specific memory B (Bmem) cells in patients during the acute phase of COVID-19. METHODS: The frequencies of RBD-binding plasmablasts and RBD-specific antibody-secreting cells (ASCs) in the peripheral blood samples collected from patients with COVID-19 were measured using flow cytometry and the ELISpot assay. RESULTS: The acute phase of COVID-19 was characterised by the transient appearance of total as well as RBD-binding plasmablasts. ELISpot analysis indicated that most patients exhibited a spontaneous secretion of RBD-specific ASCs in the circulation with good correlation between the IgG and IgM subsets. IL-21/CD40L stimulation of purified B cells induced the activation and proliferation of Bmem cells, which led to the generation of plasmablast phenotypic cells as well as RBD-specific ASCs. No correlation was observed between the frequency of Bmem cell-derived and spontaneous ASCs, suggesting that the two types of ASCs were weakly associated with each other. CONCLUSION: Our findings reveal that SARS-CoV-2-specific Bmem cells are generated during the acute phase of COVID-19. These findings can serve as a basis for further studies on the longevity of SARS-CoV-2-specific B-cell memory.