Bacitracin sensing and resistance in Staphylococcus aureus
Yuuma Yoshida
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorMiki Matsuo
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorYuichi Oogai
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorFuminori Kato
Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
Search for more papers by this authorNorifumi Nakamura
Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorMotoyuki Sugai
Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
Search for more papers by this authorHitoshi Komatsuzawa
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorYuuma Yoshida
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorMiki Matsuo
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorYuichi Oogai
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorFuminori Kato
Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
Search for more papers by this authorNorifumi Nakamura
Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorMotoyuki Sugai
Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
Search for more papers by this authorHitoshi Komatsuzawa
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Search for more papers by this authorEditor: Roger Buxton
Abstract
Bacterial two-component systems (TCSs) have been demonstrated to be associated with not only the expression of virulence factors, but also the susceptibility to antibacterial agents. In Staphylococcus aureus, 16 types of TCSs have been identified. We previously found that the inactivation of one uncharacterized TCS (designated as BceRS, MW gene ID: MW2545-2544) resulted in an increase in susceptibility to bacitracin. In this study, we focused on this TCS and tried to identify the TCS-controlled factors affecting the susceptibility to bacitracin. We found that two ABC transporters were associated with the susceptibility to bacitracin. One transporter designated as BceAB (MW2543-2542) is downstream of this TCS, while another (formerly designated as VraDE: MW2620-2621) is separate from this TCS. Both transporters showed homology with several bacitracin-resistance factors in Gram-positive bacteria. Inactivation of each of these two transporters increased the susceptibility to bacitracin. Expressions of these transporters were significantly increased by the addition of bacitracin, while this induction was not observed in the TCS-inactivated mutant. These results indicate that this TCS senses bacitracin, and also positively regulates the expression of two ABC transporters.
References
- Azevedo EC, Rios MK, Fukushima K & Campos-Takaki GM (1993) Bacitracin production by a new strain of Bacillus subtilis. Extraction, purification, and characterization. Appl Biochem Biotech 42: 1–7.
- Baba T, Takeuchi F, Kuroda M et al. (2002) Genome and virulence determinants of high virulence community-acquired MRSA. Lancet 359: 1819–1827.
- Chalker AF, Ingraham KA, Lunsford RD, Bryant AP, Bryant J, Wallis NG, Broskey JP, Pearson SC & Holmes DJ (2000) The bacA gene, which determines bacitracin susceptibility in Streptococcus pneumoniae and Staphylococcus aureus, is also required for virulence. Microbiology 146: 1547–1553.
- Fischbach MA & Walsh CT (2009) Antibiotics for emerging pathogens. Science 325: 1089–1093.
- Gardete S, Wu SW, Gill S & Tomasz A (2006) Role of VraSR in antibiotic resistance and antibiotic-induced stress response in Staphylococcus aureus. Antimicrob Agents Ch 50: 3424–3434.
- Grundmann H, Aires-de-Sousa M, Boyce J & Tiemersma E (2006) Emergence and resurgence of methicillin-resistant Staphylococcus aureus as a public-health threat. Lancet 368: 874–875.
- Howden BP, Stinear TP, Allen DL, Johnson PD, Ward PB & Davies JK (2008) Genomic analysis reveals a point mutation in the two-component sensor gene graS that leads to intermediate vancomycin resistance in clinical Staphylococcus aureus. Antimicrob Agents Ch 52: 3755–3762.
- Ito T, Okuma K, Ma XX, Yuzawa H & Hiramatsu K (2003) Insights on antibiotic resistance of Staphylococcus aureus from its whole genome: genomic island SCC. Drug Resist Update 6: 41–52.
- Johnson BA, Anker H & Meleney FL (1945) Bacitracin: a new antibiotic produced be a member of the B. subtilis group. Science 102: 376–377.
- Komatsuzawa H, Fujiwara T, Nishi H, Yamada S, Ohara M, McCallum N, Berger-Bachi B & Sugai M (2004) The gate controlling cell wall synthesis in Staphylococcus aureus. Mol Microbiol 53: 1221–1231.
- Kreiswirth B, Lofdahl S, Betley M, O'Reilly M, Schlievert P, Bergdoll M & Novick R (1983) The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature 305: 709–712.
- Kuroda M, Kuroda H, Oshima T, Takeuchi F, Mori H & Hiramatsu K (2003) Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus. Mol Microbiol 49: 807–821.
- Li M, Cha DJ, Lai Y, Villaruz AE, Sturdevant DE & Otto M (2007) The antimicrobial peptide-sensing system aps of Staphylococcus aureus. Mol Microbiol 66: 1136–1147.
- Luong TT & Lee CY (2006) The arl locus positively regulates Staphylococcus aureus type 5 capsule via an mgrA-dependent pathway. Microbiology 152: 3123–3131.
- Manson JM, Keis S, Smith JMB & Cook GM (2004) Acquired bacitracin resistance in Enterococcus faecalis is mediated by an ABC transporter and a novel regulatory protein, BcrR. Antimicrob Agents Ch 48: 3743–3748.
- Matsuo M, Kato F, Oogai Y, Kawai T, Sugai M & Komatsuzawa H (2010) Distinct two-component systems in methicillin-resistant Staphylococcus aureus can change the susceptibility to antimicrobial agents. J Antimicrob Chemoth 65: 1536–1537.
- Meehl M, Herbert S, Götz F & Cheung A (2007) Interaction of the GraRS two-component system with the VraFG ABC transporter to support vancomycin-intermediate resistance in Staphylococcus aureus. Antimicrob Agents Ch 51: 2679–2689.
- Nishi H, Komatsuzawa H, Fujiwara T, McCallum N & Sugai M (2004) Reduced content of lysyl-phosphatidylglycerol in the cytoplasmic membrane affects susceptibility to moenomycin, as well as vancomycin, gentamicin, and antimicrobial peptides, in Staphylococcus aureus. Antimicrob Agents Ch 48: 4800–4807.
- Novick RP (2003) Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48: 1429–1449.
- Ohki R, Giyanto, Tateno K, Masuyama W, Moriya S, Kobayashi K & Ogasawara N (2003) The BceRS two-component regulatory system induces expression of the bacitracin transporter, BceAB, in Bacillus subtilis. Mol Microbiol 49: 1135–1144.
- Pietiäinen M, François P, Hyyryläinen HL, Tangomo M, Sass V, Sahl HG, Schrenzel J & Kontinen VP (2009) Transcriptome analysis of the responses of Staphylococcus aureus to antimicrobial peptides and characterization of the roles of vraDE and vraSR in antimicrobial resistance. BMC Genomics 10: 429.
- Podlesek Z, Comino A, Herzog-Velikonja B, Zgur-Bertok D, Komel R & Grabna M (1995) Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance. Mol Microbiol 16: 969–976.
- Rietkötter E, Hoyer D & Mascher T (2008) Bacitracin sensing in Bacillus subtilis. Mol Microbiol 68: 768–785.
- Sakoulas G, Eliopoulos GM, Moellering RCJ, Wennersten C, Venkataraman L, Novick RP & Gold HS (2002) Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin. Antimicrob Agents Ch 46: 1492–1502.
-
Sambrook J,
Fritsch EF &
Maniatis T (1989) Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
10.1111/j.1095-8312.1996.tb01434.x Google Scholar
- Stone KJ & Strominger JL (1971) Mechanism of action of bacitracin: complexation with metal ion and C 55 – isoprenyl pyrophosphate. P Natl Acad Sci USA 68: 3223–3227.
- Subrata S, Jiwen S & Lee CY (1997) Molecular characterization and transcriptional analysis of type 8 capsule genes in Staphylococcus aureus. J Bacteriol 179: 1614–1621.
- Tsuda H, Yamashita Y, Shibata Y, Nakano Y & Koga T (2002) Genes involved in bacitracin resistance in Streptococcus mutans. Antimicrob Agents Ch 46: 3756–3764.
- Tsuji B T, Rybak MJ, Lau KL & Sakoulas G (2007) Evaluation of accessory gene regulator (agr) group and function in the proclivity towards vancomycin intermediate resistance in Staphylococcus aureus. Antimicrob Agents Ch 51: 1089–1091.
- Yin S, Daum RS & Boyle-Vavra S (2006) VraSR two-component regulatory system and its role in induction of pbp2 and vraSR expression by cell wall antimicrobials in Staphylococcus aureus. Antimicrob Agents Ch 50: 336–343.
