Holins and spanins are bacteriophage-encoded enzymes that control the onset and efficiency of bacterial cell lysis in the late stage of the bacteriophage life cycle. Their ability to compromise bacterial membranes has attracted attention in various domains. With rise in antimicrobial resistance surpassing the development of new antimicrobials, phage-encoded lysis proteins, especially holins and spanin, have now become prospective for implementation of next-generation therapeutics because of their specific activity and low impact on the host. Furthermore, understanding their complex regulation, structural diversity, and controlled lytic activity has led to the expansion of their potential in fields such as vaccine development, drug delivery, bioprocessing, and other medical or industrial applications. This review highlights recent insights into holin and spanin biology, focusing on how these lethal, membrane-disrupting proteins function, and discusses their potential use in a wide range of applications.
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