Bacterial infections remain the leading cause of death in children, the elderly, and immunocompromised patients. Andrographolide (AG), the main active component of the herb <i>Andrographis paniculata</i>, has been used for many years for anti-inflammatory and antibacterial infections. AG has an antibacterial effect on a wide variety of bacteria, which is reflected in the inhibition of bacterial pathogenic factors and the regulation of immunity to downregulate infectious inflammation caused by bacteria. In the current climate of frequently occurring antibiotic resistance, AG might be considered a promising lead for new antibacterial drug development. This review outlines the therapeutic potential of AG and its analogs in combating various bacterial infections, focusing on the mechanisms of action.

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New strategies against antibiotic-resistant bacterial pathogens are urgently needed but are not within reach. Here, we present in vitro and in vivo antimicrobial activity of TSPphg, a novel phage lysin identified from extremophilic Thermus phage TSP4 by sequencing its whole genome. By breaking down the bacterial cells, TSPphg is able to cause bacteria destruction and has shown bactericidal activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains of Klebsiella pneumoniae, in which the complete elimination and highest reduction in bacterial counts by greater than 6 logs were observed upon 50 µg/mL TSPphg treatment at 37 • C for 1 h. A murine skin infection model further confirmed the in vivo efficacy of TSPphg in removing a highly dangerous and multidrug-resistant Staphylococcus aureus from skin damage and in accelerating wound closure. Together, our findings may offer a therapeutic alternative to help fight bacterial infections in the current age of mounting antibiotic resistance, and to shed light on bacteriophage-based strategies to develop novel anti-infectives.

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