BackgroundMultidrug resistant Klebsiella pneumoniae have caused major therapeutic problems worldwide due to the emergence of the extended-spectrum β-lactamase producing strains. Although there are >10 major facilitator super family (MFS) efflux pumps annotated in the genome sequence of the K. pneumoniae bacillus, apparently less is known about their physiological relevance.Principal FindingsInsertional inactivation of kpnGH resulting in increased susceptibility to antibiotics such as azithromycin, ceftazidime, ciprofloxacin, ertapenem, erythromycin, gentamicin, imipenem, ticarcillin, norfloxacin, polymyxin-B, piperacillin, spectinomycin, tobramycin and streptomycin, including dyes and detergents such as ethidium bromide, acriflavine, deoxycholate, sodium dodecyl sulphate, and disinfectants benzalkonium chloride, chlorhexidine and triclosan signifies the wide substrate specificity of the transporter in K. pneumoniae. Growth inactivation and direct fluorimetric efflux assays provide evidence that kpnGH mediates antimicrobial resistance by active extrusion in K. pneumoniae. The kpnGH isogenic mutant displayed decreased tolerance to cell envelope stressors emphasizing its added role in K. pneumoniae physiology.Conclusions and SignificanceThe MFS efflux pump KpnGH involves in crucial physiological functions besides being an intrinsic resistance determinant in K. pneumoniae.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic has been validated as an extreme clinical calamity and has affected several socio-economic activities globally. Proven transmission of this virus occurs through airborne droplets from an infected person. The recent upsurge in the number of infected individuals has already exceeded the number of intensive care beds available to patients. These extraordinary circumstances have elicited the need for the development of diagnostic tools for the detection of the virus and, hence, prevent the spread of the disease. Early diagnosis and effective immediate treatment can reduce and prevent an increase in the number of cases. Conventional methods of detection such as quantitative real-time polymerase chain reaction and chest computed tomography scans have been used extensively for diagnostic purposes. However, these present several challenges, including prolonged assay requirements, labor-intensive testing, low sensitivity, and unavailability of these resources in remote locations. Such challenges urgently require fast, sensitive, and accurate diagnostic techniques for the timely detection and treatment of coronavirus disease 2019 (COVID-19) infections. Point-of-care biosensors that include paper- and chip-based diagnostic systems are rapid, cost-effective, and user friendly. In this article nanotechnology-based potential biosensors for SARS-CoV-2 diagnosis are discussed with particular emphasis on a lateral flow assay, a surface-enhanced Raman scattering-based biosensor, a localized surface plasmon resonance-based biosensor, Förster resonance energy transfer, an electrochemical biosensor, and artificial intelligence-based biosensors. Several biomolecules, such as nucleic acids, antibodies/enzymes, or aptamers, can serve as potential detection molecules on an appropriate platform, such as graphene oxide, nanoparticles, or quantum dots. An effective biosensor can be developed by using appropriate combinations of nanomaterials and technologies.

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Amyloid beta (Aβ) peptide aggregation is considered as one of the key hallmarks of Alzheimer’s disease (AD). Moreover, Aβ peptide aggregation increases considerably in the presence of metal ions and triggers the generation of reactive oxygen species (ROS), which ultimately leads to oxidative stress and neuronal damage. Based on the ‘multitarget-directed ligands’ (MTDLs) strategy, we designed, synthesized, and evaluated a novel series of triazole-based compounds for AD treatment via experimental and computational methods. Among the designed MTDLs [4­(a–x)], the triazole derivative 4v exhibited the most potent inhibition of self-induced Aβ42 aggregation (78.02%) with an IC50 value of 4.578 ± 0.109 μM and also disassembled the preformed Aβ42 aggregates significantly. In addition, compound 4v showed excellent metal chelating ability and maintained copper in the redox-dormant state to prevent the generation of ROS in copper-ascorbate redox cycling. Further, 4v significantly inhibited Cu2+-induced Aβ42 aggregation and disassembled the Cu2+-induced Aβ42 protofibrils as compared to the reference compound clioquinol (CQ). Importantly, 4v did not show cytotoxicity and was able to inhibit the toxicity induced by Aβ42 aggregates in SH-SY5Y cells. Molecular docking results confirmed the strong binding of 4v with Aβ42 monomer and Aβ42 protofibril structure. The experimental and molecular docking results highlighted that 4v is a promising multifunctional lead compound for AD.