title: Impairment of brain mitochondrial functions by β-hemolytic Group B Streptococcus. Effect of cardiolipin and phosphatidylcholine.
abstract: Group B Streptococcus (GBS) causes severe infection in the central nervous system. In this study, brain mitochondrial function was investigated by simulating infection of isolated mitochondria with GBS, which resulted in loss of mitochondrial activity. The β-hemolysin expressing strains GBS-III-NEM316 and GBS-III-COH31, but not the gGBS-III-COH31 that does not express β-hemolysin, caused dissipation of preformed mitochondrial membrane potential (Δψm). This indicates that β-hemolysin is responsible for decreasing of the reducing power of mitochondria. GBS-III-COH31 interacted with mitochondria causing increase of oxygen consumption, due to uncoupling of respiration, blocking of ATP synthesis, and cytochrome c release outside mitochondria. Moreover, the mitochondrial systems contributing to the control of cellular Ca(2+) uptake were lost. In spite of these alterations, mitochondrial phospholipid content and composition did not change significantly, as evaluated by MALDI-TOF mass spectrometry. However, exogenous cardiolipin (CL) and dipalmitoylphosphatidylcholine (DPPC) attenuated the uncoupling effect of GBS-III-COH31, although with different mechanisms. CL was effective only when fused to the inner mitochondrial membrane, probably reducing the extent of GBS-induced proton leakage. DPPC, which is not able to fuse with mitochondrial membranes, exerted its effect outside mitochondria, likely by shielding mitochondria against GBS β-hemolysin attack.
authors: Department of Internal Medicine, Section of Biochemistry, University of Perugia, Via Gambuli, 1, 06156, Perugia, Italy.
authors: Lara
authors: L
authors: Macchioni
authors: Katia
authors: K
authors: Fettucciari
authors: Magdalena
authors: M
authors: Davidescu
authors: Rita
authors: R
authors: Vitale
authors: Pamela
authors: P
authors: Ponsini
authors: Emanuela
authors: E
authors: Rosati
authors: Angela
authors: A
authors: Corcelli
authors: Pierfrancesco
authors: P
authors: Marconi
authors: Lanfranco
authors: L
authors: Corazzi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000096:biosynthesis*; D001921:Brain / Q000382:microbiology*; D002308:Cardiolipins / Q000494:pharmacology*; D019069:Cell Respiration / Q000502:physiology; D006460:Hemolysin Proteins / Q000096:biosynthesis*; D013058:Mass Spectrometry; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology*; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D010101:Oxygen Consumption / Q000187:drug effects; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D013290:Streptococcal Infections / Q000188:drug therapy; D013292:Streptococcus agalactiae / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002308:Cardiolipins; D006460:Hemolysin Proteins; D010713:Phosphatidylcholines; C071495:streptococcal group B hemolysin
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