The immune system is a critical factor of host survival, allowing resistance to infections and maintaining tissue integrity. The activation of immune responses requires precise regulation to assure a balance between the benefits and costs of these responses. Moreover, the theory of antagonistic pleiotropy proposes that traits beneficial to early-life fitness may sustain costs that manifest later in life, after the period of strongest natural selection, where aging introduces further complexities for cooperative defenses. As a result of this, hosts of different ages may manifest distinct disease courses despite infection with the same pathogen.

NF-κB-inducing kinase (NIK), also known as MAP3K14, is the key kinase driving noncanonical NF-κB signaling and p100 processing. Researchers from China Pharmaceutical University reported the discovery and preclinical evaluation of a novel NIK inhibitor.

Researchers from Merck & Co. reported the development of MK-7762, a novel oxazolidine with antitubercular activity designed to overcome the off-target effects of linezolid.

Multidrug-resistant (MDR) gram-positive bacteria can evade last-line therapies, such as vancomycin, daptomycin and linezolid, through the development of sophisticated resistance mechanisms that include inactivation of target enzymes, mutations in binding sites, alterations in membrane permeability and overexpression of efflux pumps.

Smartbax GmbH has in-licensed a new compound class from the antibacterial portfolio of Aicuris Anti-infective Cures AG to expand its proprietary pipeline of small-molecule antibiotics.

The range of effects caused by rhinoviruses – the pathogens responsible for the common cold – motivated scientists at Yale University to study the human nasal epithelium and uncover a previously undescribed defense mechanism. The interferon-mediated protective response in these cells can limit infection, whereas a maladaptive response tends to worsen it. Based on these findings, the researchers have identified potential therapeutic targets to reduce inflammation associated with rhinovirus infection.

In earlier work, researchers from the Institute of Medicinal Biotechnology (Beijing, China) and collaborators identified a small-molecule inhibitor (IMB-H4) of the BamA-BamD interaction. By binding to the intracellular domain of unfolded BamA, IMB-H4 disrupts the BamA-BamD assembly, leading to outer membrane damage and filamentation in gram-negative bacteria.

Using machine learning as an innovative tool for analyzing complex biological systems, researchers integrated bioinformatics with adaptive algorithms and identified dynein light chain LC8-type 2 (DYNLL2) as a key modulator of sepsis progression. Mechanistically speaking, DYNLL2 interacts with p21-activated kinase 1 (PAK1) to regulate bacterial outer membrane vesicle (OMV) internalization and caspase-11 activation.