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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.)