Actinomycetes of the genus Streptomyces are members of the phylum Actinomycetota, Gram-positive, filamentous, spore-forming bacteria. Members of the genus Streptomyces are known as producers many different bioactive natural products, such as antibiotics, antifungal, antitumor agents. Despite the large number of already known antibiotics, the actinomycetes of the genus Streptomyces still occupy an important position due to the rich variety of unique secondary metabolites and are excellent candidates for the search for new antibiotics and antifungal agents for medical purposes. Most species of the genus Streptomyces have been isolated from soils. Currently, the attention of researchers is directed to the study of actinomycetes complexes not only in soils, but also in reservoirs, plants, invertebrates. Tambukan is a lake (43°57'37"N 43°9'40"E) with bitter-salt water on Northern Caucasus. The bottom of the lake consists of a thick layer of silty mud containing sulfates and chlorides of sodium and magnesium, with a mineralization of 55-60 g/l. The medicinal water and mud of Tambukan Lake is in pelotherapy offered by health resorts and have been used by famous individuals. Thus, the actinomycetes isolated from the silty mud of Tambukan Lake are of interest not only potential producers of new antibiotics, but also as inhabitants of extreme conditions.

The goal of this study was to isolate actinomycetes from the silty mud of Tambukan Lake and to study their antimicrobial and antifungal activity. In the study ten cultures were isolated from the silty mud. A taxonomic analysis, based on the morphological, physiological, biochemical, and molecular investigation of selected strains, revealed that the isolates were affiliated to the Streptomyces genus. An assessment of antimicrobial proprieties of the ten strains, showed antimicrobial activities against fungi and bacteria: Staphylococcus aureus INA 00985, Staphylococcus aureus INA 00761 (MRSA), Micrococcus luteus ATCC 9341, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Saccharomyces cerevisiae ИНА 01042, Candida albicans ATCC 14053, Aspergillus niger ATCC 16404, Fusarium solani ВКПМ F-890, Fusarium oxysporum ВКПМ F-148. Three strains: Streptomyces fulvissimus 5T₂, Streptomyces globisporus 20T₂, Streptomyces intermedius 23T₂ demonstrated strong antimicrobial activities against fungi. These strains of the genus Streptomyces can be considered as potential producers of new antifungal agents.

This study was supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of the Federal Scientific and Technical Program for the Development of Genetic Technologies for 2019-2027 (agreement №075-15-2021-1345, unique identifier RF----193021X0012).

Since the last decade, self-medication with antibiotics (SMA) has become considerably common, which is a critical factor for driving antibiotic resistance. Individuals involved in SMA generally do not have adequate knowledge regarding the appropriate use, indications and dosage of these drugs. The objective of the present study was to investigate population SMA practices, knowledge and sociodemographic factors associated with SMA in Islamabad, Pakistan. The study has adopted a cross-sectional methodology and data collection was performed from randomly selected participants through an interview-administered questionnaire. Statistical analysis was carried out using SPSS v. 24. Out of 480 participants involved in the study, 55.6% (n=267) were male, and the total prevalence of SMA was 32.5%. Ciprofloxacin (42.9%) was the most commonly used antibiotic to treat coughs or colds, a runny nose, flu or sore throat, diarrhea or fevers, which were the relevant reasons for SMA. Findings from multivariate logistic regressions showed that predictors of SMA were male gender (95% CI: 0.383-1.005), age (95% CI: 0.317-0.953) and highest education-level (95% CI: 0.961-0.649). Despite of reasonable access to healthcare facilities, people are still obtaining antibiotics without prescription, bypassing diagnostic and consultative healthcare services. Thus, the government must implement strict healthcare policies to restrict the sales of antibiotics without prescriptions, while at the same time, targeted public awareness campaigns about the proper use of antibiotics are also required.

Introduction: Antibiotics are medicines of critical importance, but the emergence of antimicrobial resistance (AMR) is a serious threat to healthcare institutions worldwide. One of the most important hallmarks in the development of resistance is the imprudent use of antibiotics, including their non-prescription procurement and self-medication, bypassing diagnostic and consultative healthcare services. Many international campaigns have aimed to educate the general public regarding the dangers of AMR, including the European Antibiotic Awareness Day (EAAD) and the World Antibiotic Awareness Week (WAAW). Aims: The aim of this infodemiological study was to assess the changes in antibiotic-related Internet queries from Hungary, and to identify the possible association between information seeking behaviour for antibiotics and various infectious diseases. Materials and methods: Qualitative and quantitative data, and spatio-temporal distribution of queries about antibiotics were extracted from the Google Trends analysis tool for the time-period between 2010.01.01-2020.12.31. In addition, search intensity data were also collected related to the colloquial Hungarian keywords for “flu”, “common cold”, “UTI”, “sore throat”, “cough”,“sinus infection” and „probiotic”. Search intensity was expressed as relative search volume (RSV), a normalized score ranging between 0-100. Parametric tests were performed by IBM SPSS Statistics 22.0. Results: Search intensity for antibiotic-related in-formation (based on the keyword “antibiotikum”) has increased by 211.1% (26.2±4.8 vs. 55.1±12.6) between 2010 and 2020; search instensity shows significant growth even when the data was controlled for the increased number of Internet users (26.2±4.8 vs. 43.3±9.9; p<0.001). The most common related queries were “antibiotic and alcohol” (RSV range: 72-100), “antibiotic and contraceptive” (RSV range: 43-82), “antibiotic side effects” (RSV range: 39-82), “antibiotic diarrhoea” (RSV range: 44-86) and “antibiotic for UTI” (RSV range: 29-100). Educational campaigns (EAAD and WAAW) seemingly had no effect on the intensity of antibiotic-related searches (before: 66.59±15.49 vs. after: 67.91±14.07; p>0.05). Strong positive correlations were found between antibiotic-related online queries and searches related to the colloquial Hungarian keywords for flu (r=0.594), sore throat (r=0.644), cough (r=0.707) and probiotics (r=0.812), while moderately strong for the common cold (r=0.465); in every case, p values <0.001 were recorded. Conclusions: Owing to its quick and easy accessibility, the Internet has become an important source of health-related information for the public. Analysis of antibiotic-related Internet queries may be a valuable source of information of collective health utilization trends. Noteworthy associations were seen between information-seeking behaviour on commonly occurring infectious ailments.

Tuberculosis (TB) remains a major public health concern and currently is the leading cause of human death by an infectious disease. According to the World Health Organization, around 10 million people were infected with the Mycobacterium tuberculosis in 2018 and 1.5 million deceased.¹

The development of novel pharmaceutical tools to efficiently tackle tuberculosis are in the order of the day due to the rapid development of resistant strains of Mycobacterium tuberculosis.² Our group reported different classes of pharmaceutical drugs as organic salts and ionic liqudis (API-OSILs) for therapeutical applications including tuberculosis treatment.^3,4

Herein, we report novel potential formulations of a repurposed drug, the antimalarial mefloquine (MFL), which was combined with suitable and biocompatible counter-ions. Eight mefloquine organic salts were obtained by ion metathesis reaction between mefloquine hydrochloride ([MFLH][Cl]) and several organic acid sodium salts in high yields. One of the salts ([MFLH][MsO]) presented increased water solubility in comparison with [MFLH][Cl]. Moreover, all salts with the exception of [MFLH][AOT] showed improved permeability and diffusion through synthetic membranes. Finally, in vitro activity studies against Mycobacterium tuberculosis revealed that these ionic formulations exhibited up to 1.5-times lower MIC values when compared with [MFLH][Cl], in particular [MFLH][(1R)-CSA], [MFLH][(1S)-CSA] and [MFLH][HEPES].

In the case of meropenem based pharmaceutical ionic liquids, several organic cations were considered using acid-base neutralization reaction. The detailed characterization of the compounds as well as biological studies were also performed.

Nowadays, the rise of bacterial resistance gets on the podium in the race among the most worrisome Public Health issues. Currently available antibiotics are becoming ineffective to treat infectious diseases, prompting a challenging development of new antibiotics with innovative chemical scaffolds and Modes of Action (MoAs).

We recently reported the serendipitous discovery of the class of the AlkylGuanidino Ureas (AGUs), amphipathic compounds exerting a potent broad-spectrum bactericidal activity. Briefly, a bis-guanidino amine (1) was found to spontaneously generate a multicomponent mixture including oligomers through a hypothesized carbon dioxide capture. A multidisciplinary approach of in-depth MS studies, design, and synthesis led to the identification of a tetrasubstituted guanidino urea (2) endowed with Minimal Inhibitory Concentration (MIC) values ranging from 0.5 to 16 μg/mL on both Gram-positive and Gram-negative bacterial species, including antibiotic-resistant clinical isolates. Thus, we designed and synthesized a library of analogues of 2 by modifying the length of the alkyl spacers and the N-guanidino substitutions, allowing the collection of interesting preliminary structure-activity relationships (SARs).

An insight into the AGUs MoA was reached through a derivatives rational design via a molecular simplification approach and a simplified derivative (3) emerged for its antibacterial profile (MICs range 0.5-16 μg/mL). Also, we developed a modified Parallel Artificial Membrane Permeability Assay (PAMPA) by using bacterial phospholipids-endowed bilayers and poorly permeable probes to assess the ability of AGUs to disrupt the bilayers and affect their permeability. Furthermore, molecular dynamics on simulated bacterial bilayers highlighted the strong interaction of AGUs with the membranes in a “carpet-like” manner. However, in cellulo assays with propidium iodide and SYTO 9 validated the model-based experiments and confirmed the AGUs membrane-active MoA. In summary, the AGUs class is proven to be worthy of interest in the Med Chem frame for its innovative chemical structure and potent antibacterial activity, with no evidence of detrimental effects.

The adaptations that alkaliphilic fungi have developed due to their extreme habitat, promote the production of active antibiotic compounds with the potential to control microorganisms, causing infections associated with health care. The discovery of novel peptaibols from marine fungi, fungi habitats from saline and soda soils and other unique locations offer further antibiotic discovery findings from natural sources. Our results, together with previous information regarding the effect on pathogenic fungi and cancer cells, show that lipopeptaibols emericellipsins A-E (EmiA-E) from the alkaliphilic fungus E. alkalina is a promising treatment alternative to licensed antifungal drugs for invasive mycosis therapy for multidrug-resistant aspergillosis and cryptococcosis. EmiA was similar to that of amphotericin B against drug-resistant pathogenic fungi. In a continuation of our investigations into chemodiversity and yield of antimicrobial peptides, we focused in this study on the peptaibol production of the Emericellopsis strains derived from different soda and saline environments.

Thirty-eight alkaliphilic and alkalitolerant Emericellopsis strains (E.alkalina, E. cf. maritima, E. cf. terricola, Emericellopsis sp.) isolated from different saline and soda soils and belonging to marine, terrestrial, and soda soil ecological clades were investigated for EmiA biosynthesis. Our strategy to analyze other Emericellopsis sp. from different soda and saline environments proved to be useful in identifying new compounds. The analysis of the Emericellopsis sp. strains (1KS17-1, 2KS17-1) belonging to marine and terrestrial clades from chloride soils revealed another novel form with a mass of 1032.7 Da\as defined by MALDI-TOF Ms/Ms spectra as the EmiA lacking a hydroxyl (dEmiA). Bioactivity-based assays of this dEmiA form detected activity on Aspergillus niger and Candida albicans fungi with MIC 4 and 2 µg/mL respectively. EmiA displayed strong inhibitory effects on cell proliferation and viability of HCT 116 cells in a dose- and time-dependent manners and induced apoptosis.

This study was supported by the Russian Science Foundation (grant no. 21-75-00062) and the Russian Foundation for Basic Research (project no. 20-04-00992 A).