ActA is required for crossing of the fetoplacental barrier by Listeria monocytogenes.
The facultative intracellular bacterial pathogen Listeria monocytogenes induces severe fetal infection during pregnancy. Little is known about the molecular mechanisms allowing the maternofetal transmission of bacteria. In this work, we studied fetoplacental invasion by infecting mice with various mutants lacking virulence factors involved in the intracellular life cycle of L. monocytogenes. We found that the placenta was highly susceptible to bacteria, including avirulent bacteria, such as an L. monocytogenes mutant with an hly deletion (DeltaLLO) and a nonpathogenic species, Listeria innocua, suggesting that permissive trophoblastic cells, trapping bacteria, provide a protective niche for bacterial survival. The DeltaLLO mutant, which is unable to escape the phagosomal compartment of infected cells, failed to grow in the trophoblast tissue and to invade the fetus. Mutant bacteria with inlA and inlB deletion (DeltaInlAB) grew in the placenta and fetus as well as did the wild-type virulent stain (EGDwt), indicating that in the murine model, internalins A and B are not involved in fetoplacental invasion by L. monocytogenes. Pregnant mice were then infected with an actA deletion (DeltaActA) strain, a virulence-attenuated mutant that is unable to polymerize actin and to spread from cell to cell. With the DeltaActA mutant, fetal infection occurs, but with a significant delay and restriction, and it requires a placental bacterial load 2 log units higher than that for the wild-type virulent strain. Definitive evidence for the role of ActA was provided by showing that a actA-complemented DeltaActA mutant was restored in its capacity to invade fetuses. ActA-mediated cell-to-cell spreading plays a major role in the vertical transmission of L. monocytogenes to the fetus in the murine model.
Le Monnier
Alban
A
U-570 INSERM, Hôpitaux de Paris, 75730 Paris Cedex 15, France.
Autret
Nicolas
N
Join-Lambert
Olivier F
OF
Jaubert
Francis
F
Charbit
Alain
A
Berche
Patrick
P
Kayal
Samer
S
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000382:microbiology*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006360:Heat-Shock Proteins / Q000235:genetics; D006460:Hemolysin Proteins / Q000235:genetics; D018445:Infectious Disease Transmission, Vertical; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology* / Q000635:transmission; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010920:Placenta / Q000382:microbiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology*; D014327:Trophoblasts / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D008565:Membrane Proteins; D037521:Virulence Factors; C095768:inlB protein, Listeria monocytogenes; C069761:internalin protein, Bacteria; C072980:actA protein, Listeria monocytogenes; C038705:hlyA protein, Listeria monocytogenes