Similar to multicellular animals, single-cell organisms, such as bacteria show the phenomenon of programmed cell death (PCD). The PCD not only can play an important role in various physiological procedures, but also can eliminate bacteria with irreversible injuries. The PCD of single cell in a colony is for the benefits of other bacteria in the same colony to achieve the development and reproduction of the whole colony. Disturbing or destroying such PCD may provide a new way for antibiotic drug research and development.
Autophagy ; physiology ; Bacteria ; cytology ; Staphylococcus aureus ; cytology ; physiology ; Streptococcus pneumoniae ; cytology ; physiology

While ica gene of Staphylococcus epidermidis is known to undergo phase variation by insertion of IS256, the phenomenon in Staphylococcus aureus has not been evaluated. Six biofilm-positive strains were tested for the presence of biofilm-nega-tive phase-variant strains by Congo red agar test. For potential phase-variant strains, pulsed-field gel electrophoresis was done to exclude the possibility of contamination. To investigate the mechanism of the biofilm-negative phase variation, PCR for each ica genes were done. Changes of ica genes detected by PCR were confirmed by southern hybridization, and their nucleotides were analyzed by DNA sequencing. Influence of ica genes and biofilm formation on capacity for adherence to biomedical material was evaluated by comparing the ability of adhering to polyurethane sur-face among a biofilm-negative phase-variant strain and its parent strain. A biofilm-negative phase-variant S. aureus strain was detected from 6 strains tested. icaC gene of the phase-variant strain was found to be inactivated by insertion of additional gene segment, IS256. The biofilm-negative phase-variant strain showed lower adher-ing capacity to polyurethane than its parent strain. This study shows that phase variation of ica gene occurs in S. aureus by insertion of IS256 also, and this biofilm-neg-ative phase variation reduces adhering capacity of the bacteria.
Bacterial Adhesion/*physiology ; Biofilms/*growth & development ; Cell Adhesion Molecules/genetics/*metabolism ; Comparative Study ; Equipment Contamination/prevention & control ; Mutagenesis, Insertional/methods ; Mutagenesis, Site-Directed/genetics ; Phase Transition ; Polysaccharides, Bacterial/genetics/*metabolism ; *Polyurethanes ; Species Specificity ; Staphylococcus aureus/cytology/*physiology ; Structure-Activity Relationship

OBJECTIVETo investigate the effect of SP600125, a specific c-jun N-terminal protein kinase (JNK) inhibitor, on Staphylococcus aureus (S. aureus)-induced U937 cell death and the underlying mechanism.

METHODSThe human monocytic U937 cells were treated with S. aureus at different time with or without SP600125. Cell apoptosis was analyzed by flow cytometry. JNK, Bax, and caspase-3 activities were detected by Western blotting.

RESULTSS. aureus induced apoptosis in cultured U937 cells in a time-dependent manner. Expression of Bax and phospho-JNK significantly increased in S. aureus-treated U937 cells, and the level of activated caspase-3 also increased in a time-dependent manner. Inhibition of JNK with SP600125 significantly inhibited S. aureus-induced apoptosis in U937 cells.

CONCLUSIONSS. aureus can induce apoptosis in U937 cells by phosphorylation of JNK and activation of Bax and caspase-3. SP600125 protects U937 cells from apoptosis induced by S. aureus via inhibiting the activity of JNK.

Anthracenes ; pharmacology ; Apoptosis ; physiology ; Caspase 3 ; metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Macrophages ; cytology ; metabolism ; microbiology ; Mitogen-Activated Protein Kinase 8 ; antagonists & inhibitors ; metabolism ; Mitogen-Activated Protein Kinase 9 ; antagonists & inhibitors ; metabolism ; Phosphorylation ; drug effects ; Protein Kinase Inhibitors ; pharmacology ; Signal Transduction ; physiology ; Staphylococcus aureus ; physiology ; U937 Cells ; bcl-2-Associated X Protein ; metabolism