Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a plasmid encoding exfoliative toxin B

Junzo Hisatsune, Hideki Hirakawa, Takayuki Yamaguchi, Yasuyuki Fudaba, Kenshiro Oshima, Masahira Hattori, Fuminori Kato, Shizuo Kayama, Motoyuki Sugai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We report the complete nucleotide sequence and analysis of pETBTY825, a Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus TY825 is a clinical isolate obtained from an impetigo patient in 2002. The size of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype pETBTY4 (̃30 kbp). Genomic comparison of the plasmids shows that pETBTY825 has the archetype pETBTY4 as the backbone and has a single large extra DNA region of 22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside [aac(6')/aph(2'')], macrolide (msrA), and penicillin (blaZ). A plasmid deletion experiment indicated that these three resistance elements were functionally active. We retrospectively examined the resistance profile of the clinical ETB-producing S. aureus strains isolated in 1977 to 2007 using a MIC determination with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses for aac(6')/aph(2'') and msrA using purified plasmid preparations. The ETB-producing S. aureus strains began to display high resistance to GM, which was parallel with the detection of aac(6')/aph(2'') and mecA, after 1990. Conversely, there was no significant change in the ABK MIC during the testing period, although it had a tendency to slightly increase. After 2001, isolates resistant to EM significantly increased; however, msrA was hardly detected in ETB-producing S. aureus strains, and only five isolates were positive for both aac(6')/aph(2'') and msrA. In this study, we report the emergence of a fusion plasmid carrying the toxin gene etb and drug resistance genes. Prevalence of the pETB TY825 carrier may further increase the clinical threat, since ETB-producing S. aureus is closely related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS), which requires a general antimicrobial treatment.

Original languageEnglish
Pages (from-to)6131-6140
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume57
Issue number12
DOIs
Publication statusPublished - 2013 Dec
Externally publishedYes

Fingerprint

Exfoliatins
Multiple Drug Resistance
Staphylococcus aureus
Plasmids
Impetigo
Genes
Erythromycin
Gentamicins
Staphylococcal Scalded Skin Syndrome
DNA
Macrolides
Aminoglycosides
Drug Resistance
Penicillins
Sequence Analysis
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases
  • Medicine(all)

Cite this

Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a plasmid encoding exfoliative toxin B. / Hisatsune, Junzo; Hirakawa, Hideki; Yamaguchi, Takayuki; Fudaba, Yasuyuki; Oshima, Kenshiro; Hattori, Masahira; Kato, Fuminori; Kayama, Shizuo; Sugai, Motoyuki.

In: Antimicrobial Agents and Chemotherapy, Vol. 57, No. 12, 12.2013, p. 6131-6140.

Research output: Contribution to journalArticle

Hisatsune, J, Hirakawa, H, Yamaguchi, T, Fudaba, Y, Oshima, K, Hattori, M, Kato, F, Kayama, S & Sugai, M 2013, 'Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a plasmid encoding exfoliative toxin B', Antimicrobial Agents and Chemotherapy, vol. 57, no. 12, pp. 6131-6140. https://doi.org/10.1128/AAC.01062-13
Hisatsune, Junzo ; Hirakawa, Hideki ; Yamaguchi, Takayuki ; Fudaba, Yasuyuki ; Oshima, Kenshiro ; Hattori, Masahira ; Kato, Fuminori ; Kayama, Shizuo ; Sugai, Motoyuki. / Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a plasmid encoding exfoliative toxin B. In: Antimicrobial Agents and Chemotherapy. 2013 ; Vol. 57, No. 12. pp. 6131-6140.
@article{c2878d20b5f6448386b53b4696eaf830,
title = "Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a plasmid encoding exfoliative toxin B",
abstract = "We report the complete nucleotide sequence and analysis of pETBTY825, a Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus TY825 is a clinical isolate obtained from an impetigo patient in 2002. The size of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype pETBTY4 (̃30 kbp). Genomic comparison of the plasmids shows that pETBTY825 has the archetype pETBTY4 as the backbone and has a single large extra DNA region of 22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside [aac(6')/aph(2'')], macrolide (msrA), and penicillin (blaZ). A plasmid deletion experiment indicated that these three resistance elements were functionally active. We retrospectively examined the resistance profile of the clinical ETB-producing S. aureus strains isolated in 1977 to 2007 using a MIC determination with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses for aac(6')/aph(2'') and msrA using purified plasmid preparations. The ETB-producing S. aureus strains began to display high resistance to GM, which was parallel with the detection of aac(6')/aph(2'') and mecA, after 1990. Conversely, there was no significant change in the ABK MIC during the testing period, although it had a tendency to slightly increase. After 2001, isolates resistant to EM significantly increased; however, msrA was hardly detected in ETB-producing S. aureus strains, and only five isolates were positive for both aac(6')/aph(2'') and msrA. In this study, we report the emergence of a fusion plasmid carrying the toxin gene etb and drug resistance genes. Prevalence of the pETB TY825 carrier may further increase the clinical threat, since ETB-producing S. aureus is closely related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS), which requires a general antimicrobial treatment.",
author = "Junzo Hisatsune and Hideki Hirakawa and Takayuki Yamaguchi and Yasuyuki Fudaba and Kenshiro Oshima and Masahira Hattori and Fuminori Kato and Shizuo Kayama and Motoyuki Sugai",
year = "2013",
month = "12",
doi = "10.1128/AAC.01062-13",
language = "English",
volume = "57",
pages = "6131--6140",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a plasmid encoding exfoliative toxin B

AU - Hisatsune, Junzo

AU - Hirakawa, Hideki

AU - Yamaguchi, Takayuki

AU - Fudaba, Yasuyuki

AU - Oshima, Kenshiro

AU - Hattori, Masahira

AU - Kato, Fuminori

AU - Kayama, Shizuo

AU - Sugai, Motoyuki

PY - 2013/12

Y1 - 2013/12

N2 - We report the complete nucleotide sequence and analysis of pETBTY825, a Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus TY825 is a clinical isolate obtained from an impetigo patient in 2002. The size of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype pETBTY4 (̃30 kbp). Genomic comparison of the plasmids shows that pETBTY825 has the archetype pETBTY4 as the backbone and has a single large extra DNA region of 22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside [aac(6')/aph(2'')], macrolide (msrA), and penicillin (blaZ). A plasmid deletion experiment indicated that these three resistance elements were functionally active. We retrospectively examined the resistance profile of the clinical ETB-producing S. aureus strains isolated in 1977 to 2007 using a MIC determination with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses for aac(6')/aph(2'') and msrA using purified plasmid preparations. The ETB-producing S. aureus strains began to display high resistance to GM, which was parallel with the detection of aac(6')/aph(2'') and mecA, after 1990. Conversely, there was no significant change in the ABK MIC during the testing period, although it had a tendency to slightly increase. After 2001, isolates resistant to EM significantly increased; however, msrA was hardly detected in ETB-producing S. aureus strains, and only five isolates were positive for both aac(6')/aph(2'') and msrA. In this study, we report the emergence of a fusion plasmid carrying the toxin gene etb and drug resistance genes. Prevalence of the pETB TY825 carrier may further increase the clinical threat, since ETB-producing S. aureus is closely related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS), which requires a general antimicrobial treatment.

AB - We report the complete nucleotide sequence and analysis of pETBTY825, a Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus TY825 is a clinical isolate obtained from an impetigo patient in 2002. The size of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype pETBTY4 (̃30 kbp). Genomic comparison of the plasmids shows that pETBTY825 has the archetype pETBTY4 as the backbone and has a single large extra DNA region of 22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside [aac(6')/aph(2'')], macrolide (msrA), and penicillin (blaZ). A plasmid deletion experiment indicated that these three resistance elements were functionally active. We retrospectively examined the resistance profile of the clinical ETB-producing S. aureus strains isolated in 1977 to 2007 using a MIC determination with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses for aac(6')/aph(2'') and msrA using purified plasmid preparations. The ETB-producing S. aureus strains began to display high resistance to GM, which was parallel with the detection of aac(6')/aph(2'') and mecA, after 1990. Conversely, there was no significant change in the ABK MIC during the testing period, although it had a tendency to slightly increase. After 2001, isolates resistant to EM significantly increased; however, msrA was hardly detected in ETB-producing S. aureus strains, and only five isolates were positive for both aac(6')/aph(2'') and msrA. In this study, we report the emergence of a fusion plasmid carrying the toxin gene etb and drug resistance genes. Prevalence of the pETB TY825 carrier may further increase the clinical threat, since ETB-producing S. aureus is closely related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS), which requires a general antimicrobial treatment.

UR - http://www.scopus.com/inward/record.url?scp=84887488183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887488183&partnerID=8YFLogxK

U2 - 10.1128/AAC.01062-13

DO - 10.1128/AAC.01062-13

M3 - Article

C2 - 24080652

AN - SCOPUS:84887488183

VL - 57

SP - 6131

EP - 6140

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 12

ER -