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Nat Commun. 2014 Jul 9;5:4366. doi: 10.1038/ncomms5366.

G1-arrested newborn cells are the predominant infectious form of the pathogen Brucella abortus.

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1] Microorganisms biology research unit (URBM), University of Namur (UNamur), Namur, Belgium [2].
Microorganisms biology research unit (URBM), University of Namur (UNamur), Namur, Belgium.
1] Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520, USA [3] Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut 06510, USA.


Several intracellular pathogens, such as Brucella abortus, display a biphasic infection process starting with a non-proliferative stage of unclear nature. Here, we study the cell cycle of B. abortus at the single-cell level, in culture and during infection of HeLa cells and macrophages. The localization of segregation and replication loci of the two bacterial chromosomes indicates that, immediately after being engulfed by host-cell endocytic vacuoles, most bacterial cells are newborn. These bacterial cells do not initiate DNA replication for the next 4 to 6 h, indicating a G1 arrest. Moreover, growth is completely stopped during that time, reflecting a global cell cycle block. Growth and DNA replication resume later, although bacteria still reside within endosomal-like compartments. We hypothesize that the predominance of G1-arrested bacteria in the infectious population, and the bacterial cell cycle arrest following internalization, may constitute a widespread strategy among intracellular pathogens to colonize new proliferation niches.

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