Nanoprotection from SARS-COV-2: would nanotechnology help in Personal Protection Equipment (PPE) to control the transmission of COVID-19?

The coronavirus disease 2019 (COVID-19) has caused a worldwide outbreak. The severe acute respiratory syndrome coronavirus 2 virus can be transmitted human-to-human through droplets and close contact where personal protective equipment (PPE) is imperative to protect the individuals. The advancement of nanotechnology with significant nanosized properties can confer a higher form of protection. Incorporation of nanotechnology into facemasks can exhibit antiviral properties. Nanocoating on surfaces can achieve self-disinfecting purposes and be applied in highly populated places. Moreover, nano-based hand sanitizers can confer better sterilizing efficacies with low skin irritation as compared to alcohol-based hand sanitizers. The present review discusses the incorporation of nanotechnology into nano-based materials and coatings in facemasks, self-surface disinfectants and hand sanitizers, in the hope to contribute to the current understanding of PPE to combat COVID-19.

In silico genome-scale metabolic modeling and in vitro static time-kill studies of exogenous metabolites alone and with polymyxin B against Klebsiella pneumoniae.

Multidrug-resistant (MDR) Klebsiella pneumoniae is a top-prioritized Gram-negative pathogen with a high incidence in hospital-acquired infections. Polymyxins have resurged as a last-line therapy to combat Gram-negative "superbugs", including MDR K. pneumoniae. However, the emergence of polymyxin resistance has increasingly been reported over the past decades when used as monotherapy, and thus combination therapy with non-antibiotics (e.g., metabolites) becomes a promising approach owing to the lower risk of resistance development. Genome-scale metabolic models (GSMMs) were constructed to delineate the altered metabolism of New Delhi metallo-ß-lactamase- or extended spectrum ß-lactamase-producing K. pneumoniae strains upon addition of exogenous metabolites in media. The metabolites that caused significant metabolic perturbations were then selected to examine their adjuvant effects using in vitro static time-kill studies. Metabolic network simulation shows that feeding of 3-phosphoglycerate and ribose 5-phosphate would lead to enhanced central carbon metabolism, ATP demand, and energy consumption, which is converged with metabolic disruptions by polymyxin treatment. Further static time-kill studies demonstrated enhanced antimicrobial killing of 10 mM 3-phosphoglycerate (1.26 and 1.82 log10 CFU/ml) and 10 mM ribose 5-phosphate (0.53 and 0.91 log10 CFU/ml) combination with 2 mg/L polymyxin B against K. pneumoniae strains. Overall, exogenous metabolite feeding could possibly improve polymyxin B activity via metabolic modulation and hence offers an attractive approach to enhance polymyxin B efficacy. With the application of GSMM in bridging the metabolic analysis and time-kill assay, biological insights into metabolite feeding can be inferred from comparative analyses of both results. Taken together, a systematic framework has been developed to facilitate the clinical translation of antibiotic-resistant infection management.

Exogenous metabolite feeding on altering antibiotic susceptibility in Gram-negative bacteria through metabolic modulation: a review.

BACKGROUND: The rise of antimicrobial resistance at an alarming rate is outpacing the development of new antibiotics. The worrisome trends of multidrug-resistant Gram-negative bacteria have enormously diminished existing antibiotic activity. Antibiotic treatments may inhibit bacterial growth or lead to induce bacterial cell death through disruption of bacterial metabolism directly or indirectly. In light of this, it is imperative to have a thorough understanding of the relationship of bacterial metabolism with antimicrobial activity and leverage the underlying principle towards development of novel and effective antimicrobial therapies. OBJECTIVE: Herein, we explore studies on metabolic analyses of Gram-negative pathogens upon antibiotic treatment. Metabolomic studies revealed that antibiotic therapy caused changes of metabolites abundance and perturbed the bacterial metabolism. Following this line of thought, addition of exogenous metabolite has been employed in in vitro, in vivo and in silico studies to activate the bacterial metabolism and thus potentiate the antibiotic activity. KEY SCIENTIFIC CONCEPTS OF REVIEW: Exogenous metabolites were discovered to cause metabolic modulation through activation of central carbon metabolism and cellular respiration, stimulation of proton motive force, increase of membrane potential, improvement of host immune protection, alteration of gut microbiome, and eventually facilitating antibiotic killing. The use of metabolites as antimicrobial adjuvants may be a promising approach in the fight against multidrug-resistant pathogens.