Deletion of mazF increases Staphylococcus aureus biofilm formation in an ica-dependent manner.
Toxin-antitoxin (TA) systems are composed of a toxin that inhibits an essential cellular process (e.g. DNA replication, transcription, membrane integrity) and its cognate antitoxin that neutralizes the effect of the toxin. Staphylococcus aureus harbors two types of chromosomally encoded TA systems, namely mazEFsa encoding a UACAU-specific mRNA interferase and two paralogous genes of yefM-yoeBsa encoding a ribosome-dependent endoribonuclease system. However, little is known about the physiological role of MazEFsa and YefM-YoeBsa in S. aureus. Upon characterizing the phenotypes of single, double and triple gene deletion mutants, we found that mazFsa deletion led to increased biofilm formation. Subsequently, transcriptional analysis revealed that expression of intercellular adhesin (ica) gene, icaADBC, increased in a mazFsa deletion mutant. mazFsa/icaADBC double gene deletion and genetic complementation approaches provided convincing evidence that increased biofilm formation was caused by an increase in polysaccharide intercellular adhesin synthesized by icaADBC-encoded proteins. Furthermore, through the use of alanine substitutions at the conserved active residues of MazFsa, our results suggested that ica-mediated biofilm formation depended on the mRNA interferase activity of MazFsa. These findings give new insights not only into the physiological role of MazEFsa in S. aureus, but also into the regulatory mechanism of ica-dependent biofilm formation.
Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.|Department of Bacteriology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.|Department of Biochemistry and Molecular Biology, Center for Advanced Biotechnology and Medicine, Rutgers-Robert Wood Johnson Medical School, New Jersey 08854, USA.
Fuminori
F
Kato
Department of Bacteriology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Yusuke
Y
Yabuno
Department of Biochemistry and Molecular Biology, Center for Advanced Biotechnology and Medicine, Rutgers-Robert Wood Johnson Medical School, New Jersey 08854, USA.|The OCU Advanced Research Institute for Natural Science and Technology (OCARINA), Osaka City University, Osaka 558-8585, Japan.|Department of Biology and Geosciences, Graduate School of Sciences, Osaka City University, Osaka 558-8585, Japan.
Yoshihiro
Y
Yamaguchi
Department of Bacteriology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Motoyuki
M
Sugai
Department of Biochemistry and Molecular Biology, Center for Advanced Biotechnology and Medicine, Rutgers-Robert Wood Johnson Medical School, New Jersey 08854, USA.
Masayori
M
Inouye
D019943:Amino Acid Substitution; D018441:Biofilms / Q000254:growth & development*; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000235:genetics / Q000502:physiology*; D000075704:Toxin-Antitoxin Systems
D011135:Polysaccharides, Bacterial; C113579:polysaccharide intercellular adhesin
Staphylococcus aureus; biofilm; toxin-antitoxin system