Acinetobacter baumannii is an opportunistic nosocomial pathogen and one of the six most important multidrug-resistant microorganisms in hospitals worldwide. This human pathogen is responsible for a vast array of infections, of which ventilator-associated pneumonia and bloodstream infections are the most common, and mortality rates can reach 35%. Community-acquired infections have also been reported, but few strains have been recovered from environmental sources and infection reservoirs external to the hospital have not been identified. The majority of A. baumannii infections are caused by two main population clones with worldwide distribution. Infection outbreaks are often associated with multidrug resistance, including the recent emergence of strains resistant to all available antibiotics. Nevertheless, A. baumannii virulence traits and pathogenic potential have mostly remained elusive. The recent expansion of A. baumannii sequenced genomes has permitted the development of large-array phylogenomic and phenotypic analyses, which can offer valuable insights into the evolution and adaptation of A. baumannii as a human pathogen. This review summarises these recent advances, with particular focus on A. baumannii evolutionary and genomic aspects, and proposes new avenues of research.

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A fraction of the nuclear estrogen receptor ␣ (ER␣) is localized to the plasma membrane region of 17␤-estradiol (E2) target cells. We previously reported that ER␣ is a palmitoylated protein. To gain insight into the molecular mechanism of ER␣ residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ER␣ membrane localization. The cancer cell lines expressing transfected or endogenous human ER␣ (HeLa and HepG2, respectively) or the ER␣ nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ER␣ enacts ER␣ association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D 1 promoter activity, DNA synthesis). Moreover, E2 reduces both ER␣ palmitoylation and its interaction with caveolin-1, in a time-and dose-dependent manner. These data point to the physiological role of ER␣ palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation. INTRODUCTIONThe sex steroid 17␤-estradiol (E2) acts by binding to its nuclear receptors (i.e., ER␣ and ER␤) that then transactivate target genes. In addition, E2 induces rapid, nongenomic actions involving plasma membrane-associated signaling that require a membrane ER (Coleman and Smith, 2001;Kelly and Levin, 2001;Jakacka et al., 2002;Marino et al., 2002). Although different structural and functional properties have been reported for the membrane-associated ER by comparison with nuclear ER␣ and ER␤ (Ropero et al., 2002;Toran-Allerand et al., 2002;Deecher et al., 2003), immunocytochemical studies revealed the presence of a significant fraction of nuclear ER also on the plasma membrane (Pappas et al., 1995;Norfleet et al., 1999;Dan et al., 2003;Razandi et al., 2003;Arvanitis et al., 2004;Song et al., 2004). In addition, a single mRNA originates a similarly sized nuclear and membrane ER in ER␣-transfected Chinese hamster ovary and HeLa cells (Razandi et al., 1999;Marino et al., 2002Marino et al., , 2003. Thus, ER␣ localizes to both the nucleus and the plasma membrane. Moreover, the membrane ER␣ is emerging as the primary endogenous mediator of E2 rapid responses important in cell proliferation (Marino et al., 1998(Marino et al., , 2002Castoria et al., 1999Castoria et al., , 2001Razandi et al., 1999Razandi et al., , 2000Lobenhofer et al., 2000;Acconcia et al., 2004a;Fernando and Wimalasena, 2004).Debate is open regarding the structural bases and the mechanisms for ER␣ maintenance at and translocation to the plasma membrane. ER␣ does not display any intrinsic transmembrane domain (Song et al., 2004); thus, ER␣ interaction with specific membrane proteins have been proposed to explain its membrane localization Migliaccio et al., 2002;Razandi et al., 2002Razandi et al., , 2003Toran-Allerand et al., 2002;Arvanitis et al., 2004). In particular, the Ser522 re...