title: Neisseria meningitidis Lacking the Major Porins PorA and PorB Is Viable and Modulates Apoptosis and the Oxidative Burst of Neutrophils.
abstract: The bacterial pathogen Neisseria meningitidis expresses two major outer-membrane porins. PorA expression is subject to phase-variation (high frequency, random, on-off switching), and both PorA and PorB are antigenically variable between strains. PorA expression is variable and not correlated with meningococcal colonisation or invasive disease, whereas all naturally-occurring strains express PorB suggesting strong selection for expression. We have generated N. meningitidis strains lacking expression of both major porins, demonstrating that they are dispensable for bacterial growth in vitro. The porAB mutant strain has an exponential growth rate similar to the parental strain, as do the single porA or porB mutants, but the porAB mutant strain does not reach the same cell density in stationary phase. Proteomic analysis suggests that the double mutant strain exhibits compensatory expression changes in proteins associated with cellular redox state, energy/nutrient metabolism, and membrane stability. On solid media, there is obvious growth impairment that is rescued by addition of blood or serum from mammalian species, particularly heme. These porin mutants are not impaired in their capacity to inhibit both staurosporine-induced apoptosis and a phorbol 12-myristate 13-acetate-induced oxidative burst in human neutrophils suggesting that the porins are not the only bacterial factors that can modulate these processes in host cells.
authors.affiliation: School of Medical Science, Gold Coast Campus, Griffith University , Southport, QLD 4222, Australia.|Institute for Glycomics, Gold Coast Campus, Griffith University , Southport, QLD 4222, Australia.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Peak
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University , 303 East Chicago Avenue, Chicago, Illinois 60611, United States.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Chen
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University , Southport, QLD 4222, Australia.
authors.forename: Freda E-C
authors.initials: FE
authors.lastname: Jen
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University , Southport, QLD 4222, Australia.
authors.forename: Courtney
authors.initials: C
authors.lastname: Jennings
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, Brisbane, QLD 4072, Australia.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Schulz
authors.affiliation: Centre for Systems and Synthetic Biology, Brunel University , Uxbridge, Middlesex UB8 3PH, U.K.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Saunders
authors.affiliation: Centre for Systems and Synthetic Biology, Brunel University , Uxbridge, Middlesex UB8 3PH, U.K.
authors.forename: Arshad
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University , 303 East Chicago Avenue, Chicago, Illinois 60611, United States.
authors.forename: H Steven
authors.initials: HS
authors.lastname: Seifert
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University , Southport, QLD 4222, Australia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
mesh_terms: D017209:Apoptosis; D002470:Cell Survival / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D009345:Neisseria meningitidis / Q000166:cytology / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D018272:Porins / Q000172:deficiency*; D040901:Proteomics; D016897:Respiratory Burst
chemical_list: D018272:Porins; C057699:porin protein, Neisseria
keywords: Neisseria meningitidis Porins PorA PorB