TY - JOUR
T1 - Distribution and infection-related functions of bacillithiol in Staphylococcus aureus
AU - Pöther, Dierk Christoph
AU - Gierok, Philipp
AU - Harms, Manuela
AU - Mostertz, Jörg
AU - Hochgräfe, Falko
AU - Antelmann, Haike
AU - Hamilton, Chris J.
AU - Borovok, Ilya
AU - Lalk, Michael
AU - Aharonowitz, Yair
AU - Hecker, Michael
N1 - Funding Information:
We thank Katharina Ventz and Dana Clausen for excellent technical assistance and Bui Khanh Chi for help with the Northern blot experiments. 16HBE14o-cells were obtained from Jan-Peter Hildebrandt (Ernst-Moritz-Arndt-University of Greifswald) with kind permission of Dieter C. Gruenert (University of California, San Fransisco). D.C. Pöther was a recipient of a fellowship from the Alfried Krupp von Bohlen und Halbach-Stiftung (Functional Genomics Approach in Infection Biology). This work was supported by grants from the Deutsche Forschungsgemeinschaft ( SFB/TRR34 ), the Bundesministerium für Bildung und Forschung ( BaCell-SysMO2 0315784A ) and the European Union Grant BaSysBio ( LSHG-CT-2006-037469 ) to M.H., by grants from the Deutsche Forschungsgemeinschaft to H.A. ( AN746/2-1 and AN746/3-1 ) and to M.L. (SFB/TRR34), by a grant from the Biotechnology Biological Sciences Research Council ( BB/H013504/1 ) to C.J.H. and by a grant to F.H. from the Bundesministerium für Bildung und Forschung ( 03Z1CN21 ).
PY - 2013/4
Y1 - 2013/4
N2 - Bacillithiol (Cys-GlcN-malate, BSH) serves as a major low molecular weight thiol in low GC Gram-positive bacteria including Bacillus species and a variety of Staphylococcus aureus strains. These bacteria do not produce glutathione (GSH). In this study, HPLC analyses were used to determine BSH levels in different S. aureus strains. Furthermore, the role of BSH in the resistance against oxidants and antibiotics and its function in virulence was investigated. We and others (Newton, G.L., Fahey, R.C., Rawat, M., 2012. Microbiology 158, 1117-1126) found that BSH is not produced by members of the S. aureus NCTC8325 lineage, such as strains 8325-4 and SH1000. Using bioinformatics we show that the BSH-biosynthetic gene bshC is disrupted by an 8-bp duplication in S. aureus NCTC8325. The functional bshC-gene from BSH-producing S. aureus Newman (NWMN_1087) was expressed in S. aureus 8325-4 to reconstitute BSH-synthesis. Comparison of the BSH-producing and BSH-minus strains revealed higher resistance of the BSH-producing strain against the antibiotic fosfomycin and the oxidant hypochlorite but not against hydrogen peroxide or diamide. In addition, a higher bacterial load of the BSH-producing strain was detected in human upper-airway epithelial cells and murine macrophages. This indicates a potential role of BSH in protection of S. aureus during infection.
AB - Bacillithiol (Cys-GlcN-malate, BSH) serves as a major low molecular weight thiol in low GC Gram-positive bacteria including Bacillus species and a variety of Staphylococcus aureus strains. These bacteria do not produce glutathione (GSH). In this study, HPLC analyses were used to determine BSH levels in different S. aureus strains. Furthermore, the role of BSH in the resistance against oxidants and antibiotics and its function in virulence was investigated. We and others (Newton, G.L., Fahey, R.C., Rawat, M., 2012. Microbiology 158, 1117-1126) found that BSH is not produced by members of the S. aureus NCTC8325 lineage, such as strains 8325-4 and SH1000. Using bioinformatics we show that the BSH-biosynthetic gene bshC is disrupted by an 8-bp duplication in S. aureus NCTC8325. The functional bshC-gene from BSH-producing S. aureus Newman (NWMN_1087) was expressed in S. aureus 8325-4 to reconstitute BSH-synthesis. Comparison of the BSH-producing and BSH-minus strains revealed higher resistance of the BSH-producing strain against the antibiotic fosfomycin and the oxidant hypochlorite but not against hydrogen peroxide or diamide. In addition, a higher bacterial load of the BSH-producing strain was detected in human upper-airway epithelial cells and murine macrophages. This indicates a potential role of BSH in protection of S. aureus during infection.
KW - Bacillithiol
KW - BshC
KW - Glutathione
KW - Low molecular weight thiol
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=84875956912&partnerID=8YFLogxK
U2 - 10.1016/j.ijmm.2013.01.003
DO - 10.1016/j.ijmm.2013.01.003
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AN - SCOPUS:84875956912
SN - 1438-4221
VL - 303
SP - 114
EP - 123
JO - International Journal of Medical Microbiology
JF - International Journal of Medical Microbiology
IS - 3
ER -
