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Human coronaviruses are a continuous threat to the human population and have limited antiviral treatments, and the recent COVID-19 pandemic sparked interest in finding new antiviral strategies, such as natural products, to combat emerging coronaviruses. Rapid efforts in the scientific community to identify effective antiviral agents for coronaviruses remain a focus to minimize mortalities and global setbacks. In this study, an essential oil derived from Myrtus communis L. (MEO) is effective against HCoV-229E and HCoV-OC43 virus infections in comparison to two FDA-approved drugs, Remdesivir and Nirmatrelvir. Gas-chromatography and mass spectrometry were used to identify the chemical composition of MEO. Slight antioxidant activity was observed in MEO, indicating a role in oxidative stress. A dose–response curve measuring the EC50 indicates a high potency against HCoV-229E and HCoV-OC43 virus infections on Huh7.5 cells with low cytotoxicity using a PrestoBlue cell viability assay. Our findings demonstrate that MEO exhibits potent antiviral activity against HCoV-229E and HCoV-OC43 on Huh7.5 cells within a low-cytotoxicity range, but not on SARS-CoV-2. Artificial bacterial chromosome plasmids that expressed SARS-CoV-2 used for replicon—to determine viral replication and viral assembly/egress on HEK293T/17 cells—and virus-like particles on Huh7.5-AT cells—to determine viral entry and assembly/egress—showed no antiviral activity with MEO in comparison to Remdesivir. This study reveals the potential effectiveness of MEO as an alternative natural remedy to treat human coronaviruses and a potential antiviral agent for future coronavirus infections. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a major problem and a major global health concern. In total, there are 16 million deaths yearly from infectious diseases, and at least 65% of infectious diseases are caused by microbial communities that proliferate through the formation of biofilms. Antibiotic overuse has resulted in the evolution of multidrug-resistant (MDR) microbial strains. As a result, there is now much more interest in non-antibiotic therapies for bacterial infections. Among these revolutionary, non-traditional medications is quorum sensing inhibitors (QSIs). Bacterial cell-to-cell communication is known as quorum sensing (QS), and it is mediated by tiny diffusible signaling molecules known as autoinducers (AIs). QS is dependent on the density of the bacterial population. QS is used by Gram-negative and Gram-positive bacteria to control a wide range of processes; in both scenarios, QS entails the synthesis, identification, and reaction to signaling chemicals, also known as auto-inducers. Since the usual processes regulated by QS are the expression of virulence factors and the creation of biofilms, QS is being investigated as an alternative solution to antibiotic resistance. Consequently, the use of QS-inhibiting agents, such as QSIs and quorum quenching (QQ) enzymes, to interfere with QS seems like a good strategy to prevent bacterial infections. This review sheds light on QS inhibition strategy and mechanisms and discusses how using this approach can aid in winning the battle against resistant bacteria. [ABSTRACT FROM AUTHOR]

The use of essential oil (EO) in treating infected wounds is still challenging. A lot of effort has been made to make such an application more convenient. Recently, microneedles (MNDs) have been considered as a smart dermal delivery system to overcome the poor absorption and distribution, low bioavailability, and skin penetration of some drugs. The aim of our study is to evaluate the wound healing activity of juniper-EO-loaded MNDs (EO MNDs) against wounds with bacterial and fungal infection. The Polyvinylpyrrolidone (PVP) MNDs were prepared using the gel-filled mold technique and loaded with juniper EO. In vivo models were created and wounds on rats were infected with two clinically isolated bacterial strains Pseudomonas aeruginosa and Staphylococcus aureus. Furthermore, Candida albicans was used to mimic fungal infection and juniper EO MNDs were tested. The obtained results showed an improvement in wound healing which started from the third day after application of the juniper EO MNDs, and at the sixth day post-infection, the treated wounds were significantly smaller than untreated wounds. A complete healing was shown by the 12th day after infection. Furthermore, our cytotoxicity results showed a cytotoxic effect of juniper EO MNDs on epithelial cells, which explained the faster wound healing in rats. Our study showed that juniper EO MNDs represent a novel strategy in EO delivery with minimal invasion. Juniper EO MNDs demonstrated significant antimicrobial activity against both the bacterial strains Pseudomonas aeruginosa and Staphylococcus aureus and against one fungal strain, Candida albicans. Finally, application of juniper EO MNDs exerted promising activity in the treatment and healing of wound infection. [ABSTRACT FROM AUTHOR]

The clinical problem of multidrug resistance (MDR) in bacteria is due to the lack of novel antibiotics in development and the dwindling pipeline of drugs receiving market authorization. Repurposing of non-antibiotic pharmacological agents may be an attractive pathway to provide new antimicrobial drugs. The aim of the present study was to ascertain the antibacterial and adjuvant properties of a wide range of pharmaceuticals against antibiotic-susceptible and drug-resistant bacteria. Sixty-five (n = 65) pharmacological agents were included in our experiments. For Gram-positive bacteria, Staphylococcus aureus ATCC 43300 (methicillin-resistant), S. epidermidis ATCC 12228, Streptococcus pyogenes ATCC 12384 and Enterococcus faecalis ATCC 29212 were used, while for Gram-negative bacteria, Enterobacter cloacae ATCC 13047 (extended-spectrum ß-lactamase-positive), Klebsiella pneumoniae ATCC 49619, Serratia marcescens ATCC 29632 and Pseudomonas aeruginosa ATCC 27853 were included as representative strains. The minimum inhibitory concentrations (MICs) of the tested compounds were determined using the standard broth microdilution method, while a MIC reduction assay was included to ascertain the effect of the tested compounds on the MICs of standard antibiotics (ceftriaxone, ciprofloxacin and gentamicin). Seventeen and twelve drug molecules tested showed measurable antibacterial activities (MIC: 32-512 µg/mL) against Gram-positive and Gram-negative bacteria, respectively. Several compounds decreased the MICs of ciprofloxacin and gentamicin. Although there are increasing number of studies in this field, there are still significant gaps in the evidence to the potential use of non-antibiotic drugs in antimicrobial drug repurposing. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb) PE PGRS33 is a surface-exposed protein that was shown to interact with Toll-like receptor 2 on host macrophages to induce inflammatory signals and promote entry in macrophages. In this study, we investigated PE PGRS33 as a potential target of a humoral response aimed at hampering key processes in tuberculosis pathogenesis. PE PGRS33 protein was successfully expressed and purified under native condition in Escherichia coli. The purified protein retained its native functional and biological properties, showing the ability to elicit proinflammatory signals in murine and human macrophages. Interestingly, a polyclonal antiserum raised against native PE PGRS33 showed no cross-reactions with other mycobacterial proteins. The anti-PE PGRS33 serum was also able to inhibit Mtb entry into macrophages, but it did not reduce entry of the Mtb▵ pe pgrs33 strain. Addition of native recombinant PE PGRS33 to the Mtb▵ pe pgrs33 strain during infection restored the Mtb wild-type entry phenotype in macrophage. Moreover, the anti-PE PGRS33 serum was able to neutralize the proinflammatory activity of PE PGRS33 in vitro. Furthermore, mice immunized with native recombinant PE PGRS33, but not with a DNA vaccine expressing PE PGRS33, were able to restrict M. smegmatis in vivo. These results highlight the potential use of PE PGRS33 as a target of a neutralizing humoral response against tuberculosis. [ABSTRACT FROM AUTHOR]

PE_PGRSs of Mycobacterium tuberculosis (Mtb) represent a family of complex and peculiar proteins whose role and function remain elusive. In this study, we investigated PE_PGRS3 and PE_PGRS4, two highly homologous PE_PGRSs encoded by two contiguous genes in the Mtb genome. Using a gene-reporter system in Mycobacterium smegmatis (Ms) and transcriptional analysis in Mtb, we show that PE_PGRS3, but not PE_PGRS4, is specifically expressed under low phosphate concentrations. Interestingly, PE_PGRS3, but not PE_PGRS4, has a unique, arginine-rich C-terminal domain of unknown function. Heterologous expression of PE_PGRS3 in Ms was used to demonstrate cellular localisation of the protein on the mycobacterial surface, where it significantly affects net surface charge. Moreover, expression of full-length PE_PGRS3 enhanced adhesion of Ms to murine macrophages and human epithelial cells and improved bacterial persistence in spleen tissue following infection in mice. Expression of the PE_PGRS3 functional deletion mutant lacking the C-terminal domain in Ms did not enhance adhesion to host cells, showing a phenotype similar to the Ms parental strain. Interestingly, enhanced persistence of Ms expressing PE_PGRS3 did not correlate with increased concentrations of inflammatory cytokines. These results point to a critical role for the ≈ 80 amino acids long, arginine-rich C-terminal domain of PE_PGRS3 in tuberculosis pathogenesis., (© 2018 John Wiley & Sons Ltd.)