title: Apoptosis-like death in bacteria induced by HAMLET, a human milk lipid-protein complex.
abstract: BACKGROUND
  Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid.
  
  
  RESULTS
  We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death.
  
  
  CONCLUSIONS
  Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells.
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, United States of America. andersh@buffalo.edu
authors.forename: Anders P
authors.initials: AP
authors.lastname: Hakansson
authors.forename: Hazeline
authors.initials: H
authors.lastname: Roche-Hakansson
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Mossberg
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D003851:Deoxyribonucleases / Q000378:metabolism; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D007768:Lactalbumin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000494:pharmacology; D009369:Neoplasms / Q000473:pathology; D009829:Oleic Acids / Q000494:pharmacology*; D057057:Serine Proteases / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000166:cytology* / Q000187:drug effects*
chemical_list: D002843:Chromatin; C506422:HAMLET complex, human; D009829:Oleic Acids; D007768:Lactalbumin; D003851:Deoxyribonucleases; D057057:Serine Proteases; D009238:N-Acetylmuramoyl-L-alanine Amidase; D002118:Calcium