Penicillin tolerance genes of<i>Streptococcus pneumoniae</i>: the ABC‐type manganese permease complex Psa

Novak, Robert W.; Braun, Johann; Charpentier, Emmanuelle; Tuomanen, Elaine

doi:10.1046/j.1365-2958.1998.01016.x

Cited by 109 publications

(113 citation statements)

References 68 publications

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“…Because of their acute susceptibility to pneumococcal-induced apoptosis, human microglial cells were chosen as the most permissive system to screen these mutants. The following pneumococci and isogenic mutants were used: D39 capsular type 2 and R6, its nonencapsulated derivative (Rockefeller University, New York, New York, USA); the pneumolysin-negative mutant plnA -(provided by D. Briles, University of Alabama, Birmingham, Alabama, USA) (23); the pyruvate oxidase mutant spxB -, deficient in H 2 O 2 production (12); the plnA -/spxB -double mutant; the choline-binding protein A mutant cbpA -, deficient in adhesion (24); the competence-defective mutant comA - (25); the permease mutant psaA - (26), deficient in import of manganese; the IgA1 protease mutant igA - (27); the mutant zmpB - (13), deficient in a zinc metalloprotease; and lytA - (28), which is defective in autolysin.…”

Section: Methodsmentioning

confidence: 99%

Pneumococcal pneumolysin and H2O2 mediate brain cell apoptosis during meningitis

Braun¹,

Sublett²,

Freyer³

et al. 2002

J. Clin. Invest.

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132

175

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Section: Methodsmentioning

confidence: 99%

Pneumococcal pneumolysin and H2O2 mediate brain cell apoptosis during meningitis

Braun¹,

Sublett²,

Freyer³

et al. 2002

J. Clin. Invest.

Self Cite

132

175

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“…In a recent study of S. pneumoniae, a collection of transposon insertion mutants were screened for resistance to lysis by penicillin (68). Mutations in over 10 genes were obtained, and two of them were identified and characterized.…”

Section: Genes Controlling Cell Death and Survivalmentioning

confidence: 99%

“…Mutations in over 10 genes were obtained, and two of them were identified and characterized. One mutation was in a psa locus coding for an ABC-type Mn translocase (68). The mutation had a pleiotropic phenotype, and its connection to lysis is unclear.…”

Section: Genes Controlling Cell Death and Survivalmentioning

confidence: 99%

Programmed Death in Bacteria

Lewis

2000

Microbiol Mol Biol Rev

543

411

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SUMMARY Programmed cell death (PCD) in bacteria plays an important role in developmental processes, such as lysis of the mother cell during sporulation of Bacillus subtilis and lysis of vegetative cells in fruiting body formation of Myxococcus xanthus. The signal transduction pathway leading to autolysis of the mother cell includes the terminal sporulation sigma factor EςK, which induces the synthesis of autolysins CwlC and CwlH. An activator of autolysin in this and other PCD processes is yet to be identified. Autolysis plays a role in genetic exchange in Streptococcus pneumoniae, and the gene for the major autolysin, lytA, is located in the same operon with recA. DNA from lysed cells is picked up by their neighbors and recombined into the chromosome by RecA. LytA requires an unknown activator controlled by a sensory kinase, VncS. Deletion of vncS inhibits autolysis and also decreases killing by unrelated antibiotics. This observation suggests that PCD in bacteria serves to eliminate damaged cells, similar to apoptosis of defective cells in metazoa. The presence of genes affecting survival without changing growth sensitivity to antibiotics (vncS, lytA, hipAB, sulA, and mar) indicates that bacteria are able to control their fate. Elimination of defective cells could limit the spread of a viral infection and donate nutrients to healthy kin cells. An altruistic suicide would be challenged by the appearance of asocial mutants without PCD and by the possibility of maladaptive total suicide in response to a uniformly present lethal factor or nutrient depletion. It is proposed that a low rate of mutation serves to decrease the probability that asocial mutants without PCD will take over the population. It is suggested that PCD is disabled in persistors, rare cells that are resistant to killing, to ensure population survival. It is suggested that lack of nutrients leads to the stringent response that suppresses PCD, producing a state of tolerance to antibiotics, allowing cells to discriminate between nutrient deprivation and unrepairable damage. High levels of persistors are apparently responsible for the extraordinary survival properties of bacterial biofilms, and genes affecting persistence appear to be promising targets for development of drugs aimed at eradicating recalcitrant infections. PCD in unicellular eukaryotes is also considered, including aging in Saccharomyces cerevisiae. Apoptosis-like elimination of defective cells in S. cerevisiae and protozoa suggests that all unicellular life forms evolved altruistic programmed death that serves a variety of useful functions.

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“…In keeping with the actions of other pneumococcal permeases, the psa operon appears to have a regulatory role in adhesion. This operon affects the expression of choline-binding proteins on the pneumococcal surface, psa mutants demonstrating a complete absence of CbpA [18]. PsaA À and PsaD À mutants have been shown to display reduced virulence in mice and reduced adherence to lung cells in vitro [19].…”

Section: Adhesionmentioning

confidence: 99%

“…psaB À , psaC À and psaD À mutants have been noted to have a reduced capacity for transformation. Mutations within the psa operon have also been shown to confer penicillin tolerance, mutants being able to survive 103 MIC of penicillin [18].…”

Section: Adhesionmentioning

confidence: 99%