Antimicrobial peptides (AMPs) are expressed in various living organisms as first-line host defenses against potential harmful encounters in their surroundings. AMPs are short polycationic peptides exhibiting various antimicrobial activities. The principal antibacterial activity is attributed to the membrane-lytic mechanism which directly interferes with the integrity of the bacterial cell membrane and cell wall. In addition, a number of AMPs form a transmembrane channel in the membrane by self-aggregation or polymerization, leading to cytoplasm leakage and cell death. However, an increasing body of evidence has demonstrated that AMPs are able to exert intracellular inhibitory activities as the primary or supportive mechanisms to achieve efficient killing. In this review, we focus on the major intracellular targeting activities reported in AMPs, which include nucleic acids and protein biosynthesis and protein-folding, protease, cell division, cell wall biosynthesis, and lipopolysaccharide inhibition. These multifunctional AMPs could serve as the potential lead peptides for the future development of novel antibacterial agents with improved therapeutic profiles.

IFN-regulatory factor 5 (IRF-5), a member of the IRF family, is a transcription factor that has a key role in the induction of the antiviral and inflammatory response. When compared with C57BL/6 mice, Irf5 ^−/− mice show higher susceptibility to viral infection and decreased serum levels of type I IFN and the inflammatory cytokines IL-6 and TNF-α. Here, we demonstrate that IRF-5 is involved in B-cell maturation and the stimulation of Blimp-1 expression. The Irf5 ^−/− mice develop an age-related splenomegaly, associated with a dramatic accumulation of CD19 ⁺ B220 ⁻ B cells and a disruption of normal splenic architecture. Splenic B cells from Irf5 ^−/− mice also exhibited a decreased level of plasma cells. The CD19 ⁺ Irf5 ^−/− B cells show a defect in Toll-like receptor (TLR) 7- and TLR9-induced IL-6 production, and the aged Irf5 ^−/− mice have decreased serum levels of natural antibodies; however, the antigen-specific IgG1 primary response was already dependent in IRF-5 in young mice, although the IgM response was not. Analysis of the profile of transcription factors associated with plasma cell differentiation shows down-regulation of Blimp-1 expression, a master regulator of plasma cell differentiation, which can be reconstituted with ectopic IRF-5. IRF-5 stimulates transcription of the Prdm1 gene encoding Blimp-1 and binds to the IRF site in the Prdm1 promoter. Collectively, these results reveal that the age-related splenomegaly in Irf5 ^−/− mice is associated with an accumulation of CD19 ⁺ B220 ⁻ B cells with impaired functions and show the role of IRF-5 in the direct regulation of the plasma cell commitment factor Blimp-1 and in B-cell terminal differentiation.

Actinobacteria constitute prolific sources of novel and vital bioactive metabolites for pharmaceutical utilization. In recent years, research has focused on exploring actinobacteria that thrive in extreme conditions to unearth their beneficial bioactive compounds for natural product drug discovery. Natural products have a significant role in resolving public health issues such as antibiotic resistance and cancer. The breakthrough of new technologies has overcome the difficulties in sampling and culturing extremophiles, leading to the outpouring of more studies on actinobacteria from extreme environments. This review focuses on the diversity and bioactive potentials/medically relevant biomolecules of extremophilic actinobacteria found from various unique and extreme niches. Actinobacteria possess an excellent capability to produce various enzymes and secondary metabolites to combat harsh conditions. In particular, a few strains have displayed substantial antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), shedding light on the development of MRSA-sensitive antibiotics. Several strains exhibited other prominent bioactivities such as antifungal, anti-HIV, anticancer, and anti-inflammation. By providing an overview of the recently found extremophilic actinobacteria and their important metabolites, we hope to enhance the understanding of their potential for the medical world.