Mycobacterium tuberculosis (Mtb) is one of the most successful bacterial pathogens in human history. Even in the antibiotic era, Mtb is widespread and causes millions of new cases of tuberculosis each year. The ability to disrupt the host’s innate and adaptive immunity, as well as natural persistence, complicates disease control. Tuberculosis traditional therapy involves the long-term use of several antibiotics. Treatment failures are often associated with the development of resistance to one or more drugs. The development of medicines that act on new targets will expand treatment options for tuberculosis caused by multidrug-resistant or extensively drug-resistant Mtb. Therefore, the development of drugs that target virulence factors is an attractive strategy. Such medicines do not have a direct bacteriostatic or bactericidal effect, but can disarm the pathogen so that the host immune system becomes able to eliminate it. Although cell wall-associated targets are being actively studied for anti-TB drug development, other virulence factors important for adaptation and host interaction are also worth comprehensive analysis. In this review, specific Mtb virulence factors (such as secreted phosphatases, regulatory systems, and the ESX-1 secretion system) are identified as promising targets for novel anti-virulence drug development. Additionally, models for the search of virulence inhibitors are discussed, such as virtual screening in silico, in vitro enzyme inhibition assay, the use of recombinant Mtb strains with reporter constructs, phenotypic analysis using in vitro cell infection models and specific environments.

Tuberculosis is one of the most threatening infectious diseases and represents an important and significant reason for mortality in high-burden regions. The only licensed vaccine, BCG, is hardly capable of establishing long-term tuberculosis protection and is highly variable in its effectiveness. Even after 100 years of BCG use and research, we still cannot unequivocally answer the question of which immune correlates of protection are crucial to prevent Mycobacterium tuberculosis (Mtb) infection or the progression of the disease. The development of a new vaccine against tuberculosis arises a nontrivial scientific challenge caused by several specific features of the intracellular lifestyle of Mtb and the ability of the pathogen to manipulate host immunity. The purpose of this review is to discuss promising strategies and the possibilities of creating a new vaccine that could replace BCG and provide greater protection. The considered approaches include supplementing mycobacterial strains with immunodominant antigens and genetic engineering aimed at altering the interaction between the bacterium and the host cell, such as the exit from the phagosome. Improved new vaccine strains based on BCG and Mtb undergoing clinical evaluation are also overviewed.

Using the tissue-engineered constructs based on scaffolds that imitate the extracellular matrix of living tissues unveils new opportunities in the treatment of various pathologies and injuries...

Photocurable biocompatible hydrogels were fabricated from methacrylated gelatin and silk proteins (a recombinant analogue of spidroin from Nephila clavipesspider web and fibroin from the cocoons of...

2-Ethyl-6-methyl-3-hydroxypyridine succinate (EMHPS, Mexidol) is an original antioxidant and an anti-ischemic drug with the possibility of wide applications in the complex therapy of diseases, accompanied by the development of oxidative stress and ischemia; for example, ischemic stroke, chronic cerebral ischemia, and chronic heart failure. The use of EMHPS in the complex therapy of the above diseases may cause the development of drug–drug interactions, particularly pharmacokinetic interactions at the level of transporter proteins. In the present study, we evaluated the interaction of EMHPS with ABCB1 and SLCO1B1. In Caco-2 cells, it was shown that EMHPS is not a substrate of ABCB1 and that it does not affect its expression, but at the same time, it inhibits the activity of this transporter. Its inhibitory activity was inferior to verapamil—a classic inhibitor of ABCB1. In HEK293 and HEK293-SLCO1B1 cells, it was shown that EMHPS is not a substrate of SLCO1B1 either, but that it inhibited the activity of the transporter. However, its inhibitory activity was inferior to the classic inhibitor of SLCO1B1-rifampicin. Furthermore, it was found out that EMHPS does not affect SLCO1B1 expression in HepG2 cells. The approach proposed by the FDA (2020) and the International Transporter Consortium (2010) was used to assess the clinical significance of the study results. The effect of EMHPS on SLCO1B1 and the systemic inhibition of ABCB1 by EMPHS are not clinically significant, but ABCB1 inhibition by EMHPS in the gastrointestinal tract should be tested in vivo through clinical trials.