holin

Holin refers to a class of small, hydrophobic proteins encoded by bacteriophages and, in some instances, by bacterial genomes. In the lytic cycle of a phage, holins accumulate in the host cell’s cytoplasmic membrane and act as timing devices that form pores when a threshold is reached. This pore formation allows endolysins, enzymes that degrade peptidoglycan, to access the cell wall, leading to lysis and release of progeny virions.

Mechanism and classification are based on how holins function and their membrane topology. Holins are typically late-expressed and trigger lysis by forming lesions in the bacterial inner membrane. Canonical holins usually contain two or three transmembrane segments and form relatively large pores. Pinholins form numerous small lesions that rapidly dissipate the membrane potential, a process that activates associated SAR endolysins released into the periplasm. Some phages employ multiple holin types or anti-holin regulators to fine-tune lysis timing.

Distribution and role in biology. Holins are widespread among double-stranded DNA phages and have been identified in diverse phage genomes. Their primary natural role is to coordinate host cell lysis with phage replication, ensuring efficient release of progeny. In addition to their natural function, holin systems have been studied for biotechnological applications that require controlled cell disruption.

Applications and research. Holin-endolysin systems are explored for regulated lysis in bacterial production processes, enabling intracellular product release without external chemical inducers. They are also investigated in the context of phage therapy and synthetic biology as components of programmable lysis circuits. Ongoing research aims to elucidate structure–function relationships and to engineer holins with customized timing and pore properties.