Removes the 4'-phosphate group from tetra- and hexaacylated lipid A species, has no 1-phosphatase or Kdo hydrolase activity. Absence of the 4'-phosphate group renders the bacteria resistant to host-derived cationic antimicrobial peptides (CAMP), allowing it to camouflage itself from the host innate immune response, and plays a critical role in the long-term colonization of the host's stomach. Bacterial outer membrane biogenesis; LPS lipid A biosynthesis. Loss of Kdo(2)-lipid A 4'-phosphatase activity, accumulation of 4'-phosphate hexaacylated lipid A. 360-fold decrease in resistance to cationic antimicrobial peptide (CAMP) polymyxin B (PMB), increased cell-surface binding of CAMP, 20-fold decrease in resistance to endogenous antibacterial peptide Hp (rplA). Lipopolysaccharide (LPS) from the deleted strain induces the human innate immune response via Toll-like receptor 4 (TLR4) 6-fold in cultured cells (similar effects are seen with mouse cells, has no effect on TLR2-mediated induction). Almost complete loss of colonization of C57BL/6J mouse stomach (using mouse-adapted H.pylori strains B128 and X47). No changes in O-antigen or cell motility. A double lpxE-lpxF mutant accumulates 1-, 4'-bisphosphate hexaacylated lipid A, has 1000-fold decrease in resistance to PMB (a similar reduction in resistance is seen for other human-derived CAMPs), a 70-fold decrease in resistance to endogenous antibacterial peptide Hp, induces the innate immune response via TLR4 10-fold, complete loss of colonization of C57BL/6J mouse stomachs (strains B128 and X47). In this organism most lipid A is tetraacylated without a phosphate group at the 4'-position and a phosphoethanolamine residue at the 1-position. Belongs to the lipid A LpxF 4'-phosphatase family.