TY - JOUR
T1 - Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence
AU - Kaito, Chikara
AU - Saito, Yuki
AU - Nagano, Gentaro
AU - Ikuo, Mariko
AU - Omae, Yosuke
AU - Hanada, Yuichi
AU - Han, Xiao
AU - Kuwahara-Arai, Kyoko
AU - Hishinuma, Tomomi
AU - Baba, Tadashi
AU - Ito, Teruyo
AU - Hiramatsu, Keiichi
AU - Sekimizu, Kazuhisa
N1 - Funding Information:
This study was carried out in strict accordance with the recommendation in the Fundamental Guidelines for Proper Conduct of Animal Experiment and Related Activities in Academic Research Institutions under the jurisdiction of the Ministry of Education, Culture, Sports, Science and Technology, 2006. All mouse protocols followed the Regulations for Animal Care and Use of the University of Tokyo and were approved by the Animal Use Committee at the Graduate School of Pharmaceutical Science at the University of Tokyo (approval number: 19–28).
PY - 2011/2
Y1 - 2011/2
N2 - The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus.
AB - The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus.
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U2 - 10.1371/journal.ppat.1001267
DO - 10.1371/journal.ppat.1001267
M3 - Article
C2 - 21304931
AN - SCOPUS:79952210598
SN - 1553-7366
VL - 7
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 2
M1 - e1001267
ER -