1.E.14 The CidA/LrgA Holin (CidA/LrgA Holin) Family
See 1.E for a generalized description of holins.
CidA (TC# 1.E.14.1.2) and LrgA (TC# 1.E.14.1.1) of Staphylococcus aureus are homologous holin and anti-holin proteins, each with 4 putative TMSs (Ranjit et al. 2011). They are members of a large family of putative murine hydrolase exporters from a wide range of Gram-positive and Gram-negative bacteria as well as archaea. Most vary in size between 100 and 160 aas although a few are larger. It has been proposed that CidAB (23% and 32% identical to LrgAB, respectively) are involved in programmed cell death in a process that is analogous to apoptosis in eukaryotes (Bayles, 2003). They regulate and influence biofilm formation by releasing DNA from lysed cells which contributes to the biofilm matrix. CidA, a 131 aa protein with 4 putative TMSs, is believed to be the holin which exports the autolysin CidB, while LrgA may be an antiholin. If this is a general mechanism for programmed cell death, this would explain their near ubiquity in the prokaryotic world.
The cidABC operon is activated by CidR in the presence of acetic acid (Yang et al., 2005). Both CidAB and LrgAB affect biofilm formation, oxidative stress, stationary phase survival and antibiotic tolerance in a reciprocal fashion, and their genes are regulated by the LytSR two component regulatory system (Sharma-Kuinkel et al. 2009). Microfluidic techniques have been used to follow gene expression temporally and spatially during biofilm formation, revealing that both cidA and lrgA are expressed mostly in the interior of tower structures in the biofilms, regulated by oxygen availability (Moormeier et al. 2013). Analogous proteins may be linked to competence in S. mutants (Ahn et al. 2012).