## 4 Discussion  
The studies reported here both confirm and extend several of the observations made by [PERSON] et al. [15], who demonstrated CII\({}_{1-82}\), deleted for the terminal 15 amino acids, was degraded very slowly by FtsH, compared to CII WT, suggesting the terminal amino acids of the CII monomer represent an important target for FtsH proteolysis and thus CII protein stability within the cell. But they concluded that the terminal 16 amino acids were not required for CII activity, i.e., CII\({}_{1-81}\) was functional, CII\({}_{1-80}\) was non-functional. These results parallel our finding a CII\({}_{1-77}\) protein deleted for the COOH-terminal 20 amino acids was unable to complement for CII. However, we found that the terminal amino acids of WT CII\({}_{1-97}\) can influence its ability to complement, its toxicity and its effect on plasmid stability in a WT host. Whereas, CII\({}_{1-92}\) and CII\({}_{1-87}\) were as active as CII\({}_{1-97}\) for CII complementation, CII toxicity was reduced by 20-fold in CII\({}_{1-92}\) and plasmid loss was fully suppressed in CII\({}_{1-87}\). Thus, the C-terminal end of CII is not without activity in a WT host. Deletion of the C-terminal 10 residues in CII\({}_{1-87}\) eliminated complementation in hosts with five distinct point mutations in _rpoB_, each conferring rifampicin resistance, suggesting that these residues influence CII complementation. The CII complementation assay employed here assumed that _cII_ expression from a plasmid would stimulate, in trans, _pE_ transcription from infecting _imm_434 heteroimmune phages, each with a nullifying _cII_ mutation. No complementation is observed at 30 \({}^{\circ}\)C, since there is no _cII_ expression. But, expressing a high level of CII\({}_{434}\) repressor will shut down _imm_434 _pL_ and _pR_ transcription from the infecting phage, blocking plaque formation (lytic phage growth), without influencing _cII_ expression encoded on the _imm_\(\lambda\) plasmid. This assay measured two components of CII activity. Trace levels of _cII_ expression were expected at 37 \({}^{\circ}\)C (and hence turbid plaque formation but not inhibition of lytic growth). Intermediate levels of _cII_ expression were expected at 39 \({}^{\circ}\)C (compared to 42 \({}^{\circ}\)C with fully constitutive _cII_ expression), turbid plaque formation and perhaps plaque inhibition. It was found: (i) constructs exhibiting weak CII complementation supported turbid or weak-turbol plaque formation at 37 and 39 \({}^{\circ}\)C; (ii) cells defective for CII complementation gave clear pfu at 37 and 39 \({}^{\circ}\)C; and (iii) cells with full CII complementation prevented plaque formation at both 37 and 39 \({}^{\circ}\)C. [PERSON] et al. [15] suggested that CII inhibits lytic phage functions perhaps through an effect on phage DNA replication and/or Q gene expression. The results for high CII complementation, do not distinguish between (i) CII action to stimulate very high CI\({}_{434}\) expression that can shut down phage transcription, from (ii) an activity of CII that independently and perhaps non-specifically, inhibits lytic growth, e.g., by inhibiting replication, or by any other mechanism. There are some hints to tease apart the two potential actions of CII, each manifested by the inhibition of phage plating and to make sense of mutations arising within and outside of _cII_ that influence CII activity. Extrinsic factors modulate the link between high CII complementation and high CII toxicity. Early studies identified host _hflA_ and _hflB_ mutations (conferring high frequency of lysogeny phenotype) that enable \(\lambda^{+}\) and \(\lambda\)_cIII_ mutants to lysogenize these cells at high frequencies [54], suggesting higher CII activity in these cells. What seems undisputed is that the FtsH (HflB) ATP-dependent membrane protease degrades CII [15] and that the HflK-HflC proteins encoded by the _hflA_ locus can individually inhibit the FtsH-mediated proteolysis of CII in vitro [16].