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Aspergillus fumigatus is a widely distributed pathogen responsible for severe infections, particularly in immunocompromised individuals. Triazoles are the primary treatments options for Aspergillus infections; however, the emergence of acquired resistance to this antifungal class is becoming a growing concern. In this study, we investigated the potential of the antiviral drug, lopinavir (LPV) to restore the susceptibility of A. fumigatus strains to a set of azoles, while also reducing the required azole dosage for treatment of susceptible isolates. The combination of LPV with either itraconazole (ITC) or posaconazole (POS) demonstrated potent synergistic interactions against 16 out of 23 (~70%) and 21 out of 23 (~91%) A. fumigatus isolates, respectively. Moreover, the combination showed synergistic activity against other clinically important Aspergillus species, including A. niger, A. flavus, and A. brasiliensis. The fractional inhibitory concentration index (FICI) for the combinations ranged from 0.18 to 0.313 for ITC and 0.091 to 0.313 for POS, indicating strong synergistic effects. Further investigation revealed that efflux pump inhibition contributed to the synergy observed between azole and LPV. Morphological examination of the fungal cells subjected to this combinational therapy at sub-inhibitory doses showed the presence of carbohydrate granules/patches. The identification of LPV as a promising adjunct therapy holds promise for addressing the emerging challenge of azole resistance in Aspergillus species and improving treatment outcomes for patients. [ABSTRACT FROM AUTHOR]

In recent years, the field of 3D bioprinting has witnessed the intriguing development of a new type of bioink known as microbial inks. Bioinks, typically associated with mammalian cells, have been reimagined to involve microbes, enabling many new applications beyond tissue engineering and regenerative medicine. This review presents the latest advancements in microbial inks, including their definition, types, composition, salient characteristics, and biomedical applications. Herein, microbes are genetically engineered to produce 1) extrudable bioink and 2) life-like functionalities such as self-regeneration, self-healing, self-regulation, biosynthesis, biosensing, biosignaling, biosequestration, etc. We also discuss some of the promising applications of 3D extrusion printed microbial inks, such as 1) drugs and probiotics delivery, 2) metabolite production, 3) tissue engineering, 4) bioremediation, 5) biosensors and bioelectronics, 6) biominerals and biocomposites, and 7) infectious disease modeling. Finally, we describe some of the current challenges of microbial inks that needs to be addressed in the coming years, to make a greater impact in health science and technology and many other fields., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [A.D.-T. is a cofounder of Tantu Therapeutics, Inc. A.D.-T. and A.M.-B. are inventors on a US Patent #12,060,398 on programmable microbial inks. All authors declare no other competing financial interests]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biological nanopores for single-pore sensing have the advantage of size homogeneity, structural reproducibility, and channel amenability. In order to translate this to clinical applications, the functional biological nanopore must be inserted into a stable system for high-throughput analysis. Here we report factors that control the rate of pore insertion into polymer membrane and analyte translocation through the channel of viral DNA packaging motors of Phi29, T3 and T7. The hydrophobicity of aminol or carboxyl terminals and their relation to the analyte translocation were investigated. It was found that both the size and the hydrophobicity of the pore terminus are critical factors for direct membrane insertion. An N-terminus or C-terminus hydrophobic mutation is crucial for governing insertion orientation and subsequent macromolecule translocation due to the one-way traffic property. The N- or C-modification led to two different modes of application. The C-terminal insertion permits translocation of analytes such as peptides to enter the channel through the N terminus, while N-terminus insertion prevents translocation but offers the measurement of gating as a sensing parameter, thus generating a tool for detection of markers. A urokinase-type Plasminogen Activator Receptor (uPAR) binding peptide was fused into the C-terminal of Phi29 nanopore to serve as a probe for uPAR protein detection. The uPAR has proven to be a predictive biomarker in several types of cancer, including breast cancer. With an N-terminal insertion, the binding of the uPAR antigen to individual peptide probe induced discretive steps of current reduction due to the induction of channel gating. The distinctive current signatures enabled us to distinguish uPAR positive and negative tumor cell lines. This finding provides a theoretical basis for a robust biological nanopore sensing system for high-throughput macromolecular sensing and tumor biomarker detection.

RNA nanotechnology is the bottom-up self-assembly of nanometer-scale architectures, resembling LEGOs, composed mainly of RNA. The ideal building material should be (1) versatile and controllable in shape and stoichiometry, (2) spontaneously self-assemble, and (3) thermodynamically, chemically, and enzymatically stable with a long shelf life. RNA building blocks exhibit each of the above. RNA is a polynucleic acid, making it a polymer, and its negative-charge prevents nonspecific binding to negatively charged cell membranes. The thermostability makes it suitable for logic gates, resistive memory, sensor set-ups, and NEM devices. RNA can be designed and manipulated with a level of simplicity of DNA while displaying versatile structure and enzyme activity of proteins. RNA can fold into single-stranded loops or bulges to serve as mounting dovetails for intermolecular or domain interactions without external linking dowels. RNA nanoparticles display rubber- and amoeba-like properties and are stretchable and shrinkable through multiple repeats, leading to enhanced tumor targeting and fast renal excretion to reduce toxicities. It was predicted in 2014 that RNA would be the third milestone in pharmaceutical drug development. The recent approval of several RNA drugs and COVID-19 mRNA vaccines by FDA suggests that this milestone is being realized. Here, we review the unique properties of RNA nanotechnology, summarize its recent advancements, describe its distinct attributes inside or outside the body and discuss potential applications in nanotechnology, medicine, and material science.

Here, we report the isolation, identification, whole-genome sequencing, and annotation of the bacterium Yimella sp. strain RIT 621. Concentrated spent medium extract treated with ethyl acetate was found to produce bactericidal compounds against the Gram-positive bacterium Bacillus subtilis BGSC 168 and the Gram-negative bacterium Escherichia coli ATCC 25922., (Copyright © 2019 Parthasarathy et al.)