## 1 Introduction
These observations are in agreement with the known higher selectivity exerted by MsbA for hexaacylated lipid A as compared to the less favored underacylated species. Individually, all three late acyltransferases are nonessential, although \(\Delta\)_lpxL  
Figure 1: Schematic drawing depicting various players that regulate the first committed step in LPS biosynthesis catalyzed by LpxC and maintain a balance between LPS and phospholipids. Shown is the utilization of the common metabolic precursor (\(R\))-3-hydroxymyristate by LpxA and by FabZ in LPS and phospholipid biosynthesis, respectively. LpxC amounts are regulated by its turnover by the FtsH-LapB complex and at high temperature by HsIVU protease. LapC and LapD act as antagonist of LapB to regulate LPS biosynthesis as per its demand. Also shown is LapB interaction with LpxA and FabZ, thus acting as a central hub. LpxC amounts can also be fine-tuned by GcvB sRNA. exhibits a temperature-sensitive growth phenotype. However, LpxL and LpxM become essential when cardiolipin synthase A, encoded by the _clsA_ gene, is absent, suggesting that MsbA and ClsA could cooperate in LPS trafficking, although the precise mechanism of their interaction remains unknown [15; 16]. Thus, besides the regulatory control exerted by the regulation of LpxC amounts, the preferential selection of hexaacylated lipid A species by MsbA constitutes early checkpoints in controlling the proper amounts of LPS and its translocation across the inner membrane [17]. Initial studies on the regulation of LpxC deacetylase revealed that its levels are controlled in a 20-fold range in relation to the lipid A content without any increase in the corresponding mRNA levels of the encoded gene [18]. Subsequently, it was shown that LpxC is a substrate of FtsH protease and this proteolytic activity might be affected by alterations in acyl-ACP pools [5]. Such a model of FtsH-mediated proteolysis of LpxC could, in turn, provide a balance between biosynthesis of phospholipids and lipid A since both derive their fatty acyl chains from the same (\(R\))-3-hydroxyacyl-ACP pool (Figure 1) [5]. In an important breakthrough, a new essential inner membrane protein was identified and shown to co-purify with FtsH and several proteins involved in either LPS and phospholipid biosynthesis or LPS translocation, and hence designated the LPS assembly protein LapB [19]. The absence of LapB could be tolerated either in the presence of a hyperactive _fabZ_ variant that allowed an _ftsH_ deletion or when the biosynthesis of LPS was reduced [19; 20]. The co-purification of LapB with FtsH, FabZ, WaaC and Lpt proteins led to the proposal that LapB could act as a hub for LPS assembly in the IM and further cooperate with FtsH to regulate LpxC turnover [19]. More recent studies have validated these earlier observations and indeed, LapB was found to interact with LpxA, LpxC, LpxD and FabZ [21]. Similarly, recent structural and biochemical studies have shown that LpxC degradation by FtsH requires LapB [22]. However, how such LpxC degradation by FtsH-LapB is adjusted to the cellular demand for LPS remained unknown till the more recent discovery of LapC [2]. We and other independent research groups have shown that LapC acts as an antagonist of the proteolytic pathway of LpxC mediated by FtsH-LapB [6; 23; 24; 25; 26]. Our results were further supported by an examination of the properties of strains with chromosomal mutations that cause truncations in the periplasmic domain of LapC [6]. Such mutant bacteria exhibited a temperature-sensitive (Ts) phenotype, hypersensitivity to the LpxC inhibitor CHIR090, hyperdegradation of LpxC and consequently reduced levels of LPS (Figure 1). Thus, not only our group, but parallel independent studies, identified extragenic suppressors of _lapC_ mutant bacteria mapping to the _lapA/B_ operon, _lpxC_ and _ftsH_ genes [6; 23; 24; 26; 27]. Furthermore, an additional partner, LapD, which also co-purifies with LapB, was identified [28].