title: The CovS/CovR acid response regulator is required for intracellular survival of group B Streptococcus in macrophages.
abstract: Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and septicemia. The ability of this organism to survive inside phagocytic cells is poorly understood but thought to be an important step for the establishment of disease in the host. Here, we demonstrate that GBS shows prolonged survival within J774 macrophages and that the capacity to survive is not significantly changed across a diverse range of strains representing different serotypes, multilocus sequence types (MLST), and sites of clinical isolation. Using staining for the lysosome-associated membrane protein (LAMP) and by pharmacological inhibition of phagosome acidification, we demonstrate that streptococci reside in a phagosome and that acidification of the phagosome is required for GBS to survive intracellularly. Moreover, we show that the GBS two-component system CovS/CovR, which is the major acid response regulator in this organism, is required for survival inside the phagosome.
authors.affiliation: School of Biosciences, College of Life and Environmental Sciences, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Cumley
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Anthony
authors.forename: Robin C
authors.initials: RC
authors.lastname: May
mesh_terms: D000818:Animals; D016667:Bacterial Capsules; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D000071677:Histidine Kinase; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes; D010860:Pigments, Biological; D017382:Reactive Oxygen Species; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013292:Streptococcus agalactiae / Q000235:genetics* / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D006460:Hemolysin Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010860:Pigments, Biological; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D037521:Virulence Factors; D054353:Perforin; C071495:streptococcal group B hemolysin; C534547:CovS protein, Streptococcus pyogenes; D000071677:Histidine Kinase