title: InlP, a New Virulence Factor with Strong Placental Tropism.
abstract: Intrauterine infection is a major detriment for maternal-child health and occurs despite local mechanisms that protect the maternal-fetal interface from a wide variety of pathogens. The bacterial pathogen Listeria monocytogenes causes spontaneous abortion, stillbirth, and preterm labor in humans and serves as a model for placental pathogenesis. Given the unique immunological environment of the maternal-fetal interface, we hypothesized that virulence determinants with placental tropism are required for infection of this tissue. We performed a genomic screen in pregnant guinea pigs that led to the identification of 201 listerial genes important for infection of the placenta but not maternal liver. Among these genes was lmrg1778 (lmo2470), here named inlP, predicted to encode a secreted protein that belongs to the internalin family. InlP is conserved in virulent L. monocytogenes strains but absent in Listeria species that are nonpathogenic for humans. The intracellular life cycle of L. monocytogenes deficient in inlP (ΔinlP) was not impaired. In guinea pigs and mice, InlP increased the placental bacterial burden by a factor of 3 log10while having only a minor role in other maternal organs. Furthermore, the ΔinlP strain was attenuated in intracellular growth in primary human placental organ cultures and trophoblasts. InlP is a novel virulence factor for listeriosis with a strong tropism for the placenta. This virulence factor represents a tool for the development of new modalities to prevent and treat infection-related pregnancy complications.
authors.affiliation: Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA.|Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Faralla
authors.affiliation: Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California, USA.|Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Gabrielle A
authors.initials: GA
authors.lastname: Rizzuto
authors.affiliation: Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA.|Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Lowe
authors.affiliation: Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA.|Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Byoungkwan
authors.initials: B
authors.lastname: Kim
authors.affiliation: Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA.|Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Cara
authors.initials: C
authors.lastname: Cooke
authors.affiliation: Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA.|Biomedical Sciences Program, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Shiow
authors.affiliation: Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, USA anna.bakardjiev@ucsf.edu.|Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California, USA.|Biomedical Sciences Program, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Anna I
authors.initials: AI
authors.lastname: Bakardjiev
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006168:Guinea Pigs; D008089:Listeria monocytogenes / Q000378:metabolism*; D008088:Listeriosis / Q000382:microbiology*; D051379:Mice; D009068:Movement; D010920:Placenta / Q000382:microbiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors