The nucleoid occlusion factor Noc controls DNA replication initiation in Staphylococcus aureus

• Published in: PLoS genetics Vol. 13; no. 7; p. e1006908
• Main Authors: Pang, Ting, Wang, Xindan, Lim, Hoong Chuin, Bernhardt, Thomas G, Rudner, David Z
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.07.2017; Public Library of Science (PLoS)
• Subjects: Bacteria; Bacterial Proteins - genetics; Biology and Life Sciences; Cell division; Cell Division - genetics; Cell size; Chromosome Segregation; Chromosomes; Chromosomes, Bacterial - genetics; Deactivation; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA replication; DNA Replication - genetics; DNA sequencing; DNA-Binding Proteins - genetics; E coli; Funding; Gene expression; Genetic aspects; Infectious diseases; Medical schools; Medicine and Health Sciences; Methods; Mutation; Observations; Occlusion; Overexpression; Pathogens; Proteins; Regulators; Replication; Replication initiation; Research and Analysis Methods; RNA polymerase; Roles; Spatial discrimination; Staphylococcal Infections - genetics; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - pathogenicity
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006908

Successive division events in the spherically shaped bacterium Staphylococcus aureus are oriented in three alternating perpendicular planes. The mechanisms that underlie this relatively unique pattern of division and coordinate it with chromosome segregation remain largely unknown. Thus far, the only known spatial regulator of division in this organism is the nucleoid occlusion protein Noc that inhibits assembly of the cytokinetic ring over the chromosome. However, Noc is not essential in S. aureus, indicating that additional regulators are likely to exist. To search for these factors, we screened for mutants that are synthetic lethal with Noc inactivation. Our characterization of these mutants led to the discovery that S. aureus Noc also controls the initiation of DNA replication. We show that cells lacking Noc over-initiate and mutations in the initiator gene dnaA suppress this defect. Importantly, these dnaA mutations also partially suppress the division problems associated with Δnoc. Reciprocally, we show that over-expression of DnaA enhances the over-initiation and cell division phenotypes of the Δnoc mutant. Thus, a single factor both blocks cell division over chromosomes and helps to ensure that new rounds of DNA replication are not initiated prematurely. This degree of economy in coordinating key cell biological processes has not been observed in rod-shaped bacteria and may reflect the challenges posed by the reduced cell volume and complicated division pattern of this spherical pathogen.