Modulation of Neisseria Porin (PorB) by Cytosolic ATP/GTP of Target Cells: Parallels between Pathogen Accommodation and Mitochondrial Endosymbiosis

Abstract

PorB of the pathogenic Neisseria species belongs to the large family of pore-forming proteins (porins) produced by gram-negative bacteria. PorB is exceptional in that it is capable of translocating vectorially into membranes of infected target cells and functions in the infection process. Here we report on an unexpected similarity between Neisserial PorB and mitochondrial porins. Both porin classes interact with purine nucleoside triphosphates, which down-regulate pore size and cause a shift in voltage dependence and ion selectivity. Patch-clamp analyses indicate that PorB channel activity is tightly regulated in intact epithelial cells. In light of recent findings on the pivotal role of PorB in virulence and the prevention of phagosome lysosome fusion, these data provide important mechanistic clues on the intracellular pathogen accommodation reminiscent of mitochondrial endosymbiosis.

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

“…Their pore function in the bacteria is regulated by a similar gating mechanism, only observed in N. meningitidis PorB, N. gonorrhoeae PIA and PIB, N.lactamica and N. polysaccharea. A similar pore function, regulated by ATP and GTP, has been described in host cells upon porin insertion in the cell membrane [75].…”

Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells

“…For example, the protozoans T. gondii (Nichols et al, 1983;Beckers et al, 1994) and P. falciparum (Stewart et al, 1986) have speci®c secretory organelles called rhoptries, which are capable of secreting proteins and lipids to the parasitophorous vacuoles (Sibley et al, 1986;Dluzewski et al, 1992). Another example is the outer membrane protein PorB of N. gonorrhoeae, which translocates from the outer membrane of the gonococci into host cell membranes (Rudel et al, 1996). PorB is able to modify the maturation of latex beads containing phagosomes in primary human macrophages (Mosleh et al, 1998), indicating a possible role of this protein in the modulation of neisserial phagosome maturation.…”

Calcium, ATP and nuclear pore channel gating

“…The observations were interpreted by the authors to result from conformational changes [49]. Although it is possible that the NPCC conformation was affected by our experimental maneuvers, the lack of effect after repeated treatment with the Ca+ATP system does not support this alternative.…”

“…Rudel et al [49] showed that ATP and GTP interrupt the activity of the porin-PorB bacterial channel -a structure whose conductance and channel diameter are 1500 pS and 10 nm, respectively [49]. The observations were interpreted by the authors to result from conformational changes [49].…”

“…Although it is possible that the NPCC conformation was affected by our experimental maneuvers, the lack of effect after repeated treatment with the Ca+ATP system does not support this alternative. Unfortunately, since Rudel et al [49] did not try repeated exposures, a direct comparison of these two different channels is not possible. Our study supports the idea that [Ca 2+ ] NE and ATP, when present in conjunction with all the elements required for MMT, cause a transient reduction of single NPCC ion conductance, γ (and thus NE ion permeability), by promoting transient channel plugging during MMT.…”