TamAB is regulated by PhoPQ and functions in outer membrane homeostasis during pathogenesis.

survive and replicate in macrophages, which normally kill bacteria by exposing them to a variety of harsh conditions and antimicrobial effectors, many of which target the bacterial cell envelope. The PhoPQ two-component system responds to the phagosome environment and induces factors that protect the outer membrane, allowing adaptation and growth in the macrophage. We show that PhoPQ induces the transcription of the operon both and in macrophages. The TamA protein is structurally similar to BamA, an essential protein in the Bam complex that assembles β-barrel proteins in the outer membrane, while TamB is an AsmA-family protein implicated in lipid transport between the inner and outer membranes. We show that the Bam machinery is stressed under low Mg, low pH conditions that mimic the phagosome. Not surprisingly, mutations affecting Bam function confer significant virulence defects. Although loss of TamAB alone confers no virulence defect, a deletion confers a synthetic phenotype in mutant backgrounds in animals and macrophages, and upon treatment with vancomycin or sodium dodecyl sulfate. Mutations affecting YhdP, which functions in partial redundancy with TamB, also confer synthetic phenotypes with mutations in the animal, but this interaction is not evident . Thus, in the harsh phagocytic environment of the macrophage, the outer membrane Bam machinery is compromised, and the TamAB system, and perhaps other PhoPQ-regulated factors, is induced to compensate. It is most likely that TamAB and other systems assist the Bam complex indirectly by affecting outer membrane properties. IMPORTANCE The TamAB system has been implicated in both outer membrane protein localization and phospholipid transport between the inner and outer membranes. We show that the β-barrel protein assembly complex, Bam, is stressed under conditions thought to mimic the macrophage phagosome. TamAB expression is controlled by the PhoPQ two-component system and induced in macrophages. This system somehow compensates for the Bam complex as evidenced by the fact that mutations affecting the two systems confer synthetic phenotypes in animals, macrophages, and in the presence of vancomycin or SDS. This study has implications concerning the role of TamAB in outer membrane homeostasis. It also contributes to our understanding of the systems necessary for to adapt and reproduce within the macrophage phagosome.