Recent advancements in bidimensional nanoparticles production such as Graphene (G) and Graphene oxide (GO) have the potential to meet the need for highly functional personal protective equipment (PPE) against SARS-CoV-2 infection. The ability of G and GO to interact with microorganisms provides an opportunity to develop engineered textiles for use in PPE and limit the spread of COVID-19. PPE in current use in high-risk settings for COVID transmission provide only a physical barrier that decreases infection likelihood and does not inactivate the virus. Here, we show that virus pre-incubation with soluble GO inhibits SARS-CoV-2 infection of VERO cells. Furthermore, when G/GO functionalized polyurethane or cotton were in contact SARS-CoV-2, the infectivity of the fabric was nearly completely inhibited. The findings presented here constitute an important innovative nanomaterial-based strategy to significantly increase PPE efficacy in protection against the SARS-CoV-2 virus that may implement water filtration, air purification, and diagnostics methods.

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.

GO trapping reduces mycobacteria entry in macrophages when the bacilli are in the external environment: a possible therapeutic strategy for tuberculosis.

Global pandemic management represents a serious issue for health systems. In some cases, repurposing of existing medications might help find compounds that have the unexpected potential to combat microorganisms. In the same way, changing cell–drug interaction by nanotechnology could represent an innovative strategy to fight infectious diseases. Tuberculosis (TB) remains one of the most alarming worldwide infectious diseases and there is an urgent need for new drugs and treatments, particularly for the emergence and spread of drug-resistant Mycobacterium tuberculosis (Mtb) strains. New nanotechnologies based on carbon nanomaterials are now being considered to improve anti-TB treatments, and graphene oxide (GO) showed interesting properties as an anti-TB drug. GO, which preferentially accumulates in the lungs and is degraded by macrophagic peroxidases, can trap Mycobacterium smegmatis and Mtb in a dose-dependent manner, reducing the entry of bacilli into macrophages. In this paper, combinations of isoniazid (INH), amikacin (AMK) and linezolid (LZD) and GO anti-mycobacterial properties were evaluated against Mtb H37Rv by using a checkerboard assay or an in vitro infection model. Different GO effects have been observed when incubated with INH, AMK or LZD. Whereas the INH and AMK anti-mycobacterial activities were blocked by GO co-administration, the LZD bactericidal effect increased in combination with GO. GO-LZD significantly reduced extracellular mycobacteria during infection and was able to kill internalized bacilli. GO-LZD co-administration is potentially a new promising anti-TB treatment at the forefront in fighting emerging antibiotic-resistant Mtb strains where LZD administration is suggested. This innovative pharmacological approach may lead to reduced treatment periods and decreased adverse effects. More importantly, we demonstrate how nanomaterials–drugs combinations can represent a possible strategy to quickly design drugs for pandemics treatment.

Recent advancements in bidimensional nanoparticles such as Graphene nanoplatelets (G) and the derivative Graphene oxide (GO) have the potential to meet the need for highly functional personal protective equipment (PPE) that confers increased protection against SARS-CoV-2 infection and the spread COVID-19. The ability of G and GO to interact with and bind microorganisms as well as RNA and DNA provides an opportunity to develop engineered textiles for use in PPE. The face masks widely used in health care and other high-risk settings for COVID transmission provide only a physical barrier that decreases likelihood of infection and do not inactivate the virus. Here, we show pre-incubation of viral particles with free GO inhibits SARS-CoV-2 infection of VERO cells. Highly relevant to PPE materials, when either polyurethane or cotton material was loaded with G or GO and culture medium containing SARS-CoV-2 viral particles either filtered through or incubated with the functionalized materials, the infectivity of the medium was nearly completely inhibited. The findings presented here constitute an important nanomaterials-based strategy to significantly increase face mask and other PPE efficacy in protection against the SARS-CoV-2 virus and COVID-19 that may be applicable to additional anti-SARS-CoV-2 measures including water filtration, air purification, and diagnostics.

No abstract

Graphene Oxide has been proposed as a potential adjuvant to develop improved anti-TB treatment, thanks to its activity in entrapping mycobacteria in the extracellular compartment limiting their entry in macrophages. Indeed, when administered together with linezolid, Graphene Oxide significantly enhanced bacterial killing due to the increased production of Reactive Oxygen Species. In this work, we evaluated Graphene Oxide toxicity and its anti-mycobacterial activity on human peripheral blood mononuclear cells. Our data show that Graphene Oxide, different to what is observed in macrophages, does not support the clearance of Mycobacterium tuberculosis in human immune primary cells, probably due to the toxic effects of the nano-material on monocytes and CD4+ lymphocytes, which we measured by cytometry. These findings highlight the need to test GO and other carbon-based nanomaterials in relevant in vitro models to assess the cytotoxic activity while measuring antimicrobial potential.

PE_PGRS proteins of Mycobacterium tuberculosis ( Mtb ) constitute a large family of complex modular proteins whose role is still unclear. Among those, we have previously shown, using the heterologous expression in Mycobacterium smegmatis , that PE_PGRS3 containing a unique arginine-rich C-terminal domain, promotes adhesion to host cells. In this study, we investigate the role of PE_PGRS3 and its C-terminal domain directly in Mtb using functional deletion mutants. The results obtained here show that PE_PGRS3 is localized on the mycobacterial cell wall and its arginine-rich C-terminal region protrudes from the mycobacterial membrane and mediates Mtb entry into epithelial cells. Most importantly, this positively charged helical domain specifically binds phosphorylated phosphatidylinositols and cardiolipin, whereas it is unable to bind other phospholipids. Interestingly, administration of cardiolipin and phosphatidylinositol but no other phospholipids was able to turn-off expression of pe_pgrs 3 activated by phosphate starvation conditions. These findings suggest that PE_PGRS3 has the key role to serve as a bridge between mycobacteria and host cells by interacting with specific host phospholipids and extracting them from host cells, for their direct integration or as a source of phosphate, during phases of TB pathogenesis when Mtb is short of phosphate supply.