Evolution of a novel IMP-6 producing P. aeruginosa in a long-term care facility in Japan

概要

඲ᩥせ⣙
Evolution of a novel IMP-6 producing P. aeruginosa in a long-term carefacility in Japan
by MITSUYASU IKEDA

Thesis Director:
Dr. Motoyuki Sugai

2017 ᖺ 6 ᭶㸪ᗈᓥ┴ෆࡢ࠶ࡿ㛗ᮇ⒪㣴ᆺ་⒪᪋タ㸦LTCF㸧ࡢධ㝔ᝈ⪅࠿ࡽ࢝ࣝࣂ࣌ࢿ࣒⪏ᛶ
⭠ෆ⣽⳦┠⣽⳦㸦CRE㸧ࡀ᳨ฟࡉࢀࡓࠋࡑࡢᝈ⪅ࡣ↓⑕≧࡛ CRE ࡢಖ⳦⪅࡛࠶ࡗࡓࠋࡑࡢᚋ㸪
ᗈᓥ኱Ꮫ 㝔ෆឤᰁ⑕ࣉࣟࢪ࢙ࢡࢺ◊✲ࢭࣥࢱ࣮ࡀ LTCF ࡛ࡢ CRE ࡢศᏊ␿Ꮫⓗ࡞ࢧ࣮࣋࢖ࣛ
ࣥࢫࢆᐇ᪋ࡍࡿࡇ࡜࡟࡞ࡗࡓࠋ24 ྡࡢධ㝔ᝈ⪅ࢆᑐ㇟࡟ၻ⑱㸪ᒀ㸪౽ࢆ᥇ྲྀࡋಖ⳦ㄪᰝࢆ⾜ࡗ
ࡓࠋࡲࡓྛࣇࣟ࢔ࡢฎ⨨ᐊࡢࢩࣥࢡࡸ᤼Ỉ⁁ࢆ୰ᚰ࡟ィ 40 ࣧᡤ࠿ࡽ⎔ቃࢧࣥࣉࣝࢆ᥇ྲྀࡋࡓࠋ
ࢫࢡ࣮ࣜࢽࣥࢢ࡟ࡼࡾ㸪ᝈ⪅ 24 ே୰ 23 ே㸪࠾ࡼࡧ⑓㝔⎔ቃ 40 ࣧᡤ୰ 20 ࣧᡤ࠿ࡽィ 140 ᰴࡢ
⸆๣⪏ᛶ⳦㸦ARB㸧ࢆ᳨ฟࡋࡓࠋPCR ࢆ⏝࠸࡚ゎᯒࡋࡓ⤖ᯝ㸪7 ⳦✀ 67 ᰴࡢ࢝ࣝࣂ࣌ࢿ࣐࣮ࢮ
⏘⏕⳦㸦CPO㸧࠾ࡼࡧ 5 ⳦✀ 20 ᰴࡢᇶ㉁ᣑᙇᆺș-ࣛࢡࢱ࣐࣮ࢮ㸦ESBL㸧⏘⏕ᰴ㸦࢝ࣝࣂ࣌ࢿ
࣐࣮ࢮྠ᫬⏘⏕ᰴࡣ㝖ࡃ㸧ࢆ᳨ฟࡋࡓࠋ᳨ฟࡋࡓ࢝ࣝࣂ࣌ࢿ࣐࣮ࢮ㑇ఏᏊࡣ㸪blaIMP-1㸸6 ᰴ㸪

blaIMP-6㸸59 ᰴ㸪blaTMB-1㸸2 ᰴ࡛࠶ࡗࡓࠋPseudomonas aeruginosa ࠿ࡽࡶ blaIMP-6 ࢆ 1 ᰴ᳨ฟ
ࡋࡓࠋ51 ᰴࡢ blaIMP-6 ಖ᭷ CPO ࢆ blaIMP-6 ࣉࣛࢫ࣑ࢻ pKPI-6 ࢆࣜࣇ࢓ࣞࣥࢫ࡜ࡋ࡚ẚ㍑ࡋࡓ
⤖ᯝ㸪50 ᰴࡢ blaIMP-6 ࢆྵࡴ DNA ࡣࣉࣛࢫ࣑ࢻ඲య࡟࣐ࢵࣆࣥࢢࡉࢀࡓࡀ㸪P. aeruginosa
TC16G 㸦ST235㸧ࡣ blaIMP-6 integron ࡢࡳࡀ࣐ࢵࣆࣥࢢࡉࢀࡓࠋࡲࡓ blaIMP-6 integron 㡿ᇦࡢ
ሷᇶ㓄ิࢆヲ⣽࡟ゎᯒࡋࡓ⤖ᯝ㸪blaIMP-6 ࡢୖὶ࡟఩⨨ࡍࡿ aacA4’-3 ࡟ pKPI-6 ࡢ aacA4’-3 ࡜
ࡣ␗࡞ࡿ 1 ሷᇶከᆺ㸦C305T㸧ࢆㄆࡵࡓࠋࡇࡢ୍ሷᇶከᆺࡣ LTCF ෆ࡛ศ㞳ࡉࢀࡓ඲࡚ࡢ blaIMP6 ࢆ᭷ࡍࡿ

CPO ࡀಖ᭷ࡋ࡚࠸ࡓࠋ୍᪉࡛㸪ᗈᓥ┴ෆࡢ 12 ᪋タࢆᑐ㇟࡜ࡋ࡚㝔ෆឤᰁ⑕ࣉࣟࢪ࢙

ࢡࢺ◊✲ࢭࣥࢱ࣮ࡀ 2009 ᖺ࠿ࡽᐇ᪋ࡋ࡚ࡁࡓ ESBL ⏘⏕⳦࣭CPO ࢧ࣮࣋࢖ࣛࣥࢫ࡛ศ㞳ࡉࢀ
ࡓ 84 ᰴࡢ blaIMP-6 ಖ᭷ CPO ࡜㏆␥ᆅ༊࡛ 2006-2011 ᖺ࡟ศ㞳ࡉࢀࡓ blaIMP-6 ಖ᭷ CPO ࢆㄪ࡭
ࡓ⤖ᯝ㸪ᗈᓥ┴ෆࡢ௚᪋タ࡛ࡣ 1 ᪋タࡢᛴᛶᮇ⑓㝔㸦B Hospital㸧࠿ࡽࡢࡳ 2016㸪2017 ᖺ࡟ 2
ᰴࡢ୍ሷᇶከᆺࡀ᳨ฟࡉࢀࡓࠋࡲࡓ㸪ࡇࡢ୍ሷᇶከᆺࡣ㏆␥ᆅ༊ࡢᛴᛶᮇ⑓㝔㸦A Hospital㸧࠿
ࡽ 1 ᰴࡢࡳ᳨ฟࡉࢀࡓࠋpKPI-6 ࢆࣜࣇ࢓ࣞࣥࢫ࡜ࡋ࡚ blaIMP-6 ಖ᭷ࣉࣛࢫ࣑ࢻ࡜ࡢࢥ࢔ࢤࣀ࣒
⣔⤫ᶞ࡟ࡼࡿゎᯒࢆᐇ᪋ࡋࡓ⤖ᯝ㸪B Hospital ࠿ࡽ 2016 ᖺ࡟᳨ฟࡉࢀࡓᰴࡣ LTCF ࡜ࡣูࡢ
ࢡࣛࢫࢱ࣮࡟ᒓࡋ࡚࠸ࡓࡀ㸪2017 ᖺ࡟ B Hospital ࠿ࡽ᳨ฟࡉࢀࡓᰴ࡜㏆␥⏤᮶ A Hospital ࠿
ࡽ᳨ฟࡉࢀࡓᰴࡣ LTCF ࡜ྠࡌࢡࣛࢫࢱ࣮࡟ᒓࡋ࡚࠸ࡓࠋ blaIMP-6 ࡢಖ᭷ࡀ☜ㄆࡉࢀࡓ P.

aeruginosa TC16G ࡢ blaIMP-6 integron ࡢ࿘㎶ᵓ㐀ࢆゎᯒࡋࡓ⤖ᯝ㸪P. aeruginosa P34 ᰴࡢᰁ
Ⰽయ㸦accession no. CP032552㸧࡜ᵓ㐀ࡀ㢮ఝࡋ㸪 blaIMP-6 integron ࡣᰁⰍయୖࡢ㡿ᇦ㸦nt
2,489,981㹼nt 2,498,421㸧࡟⤌ࡳ㎸ࡲࢀ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡲࡓ㸪TC16G ᰴࡢ blaIMP6

integron ࡢୖὶ࡟ࡣ tnpR ࠾ࡼࡧ tnpA ࢆㄆࡵࡓࠋTC16G ᰴࡢ blaIMP-6 integron ࡢ⬺ⴠࡢྍ

⬟ᛶࢆホ౯ࡍࡿࡓࡵ࡟㸪TC16G ᰴࢆ 10 ᅇ⥅௦ᇵ㣴ࡋࡓᇵ㣴ᾮࢆᇵᆅ࡟ᧈࡁ㸪Ⓨ⫱ࡋࡓࢥࣟࢽ
࣮ࢆゎᯒࡋࡓ⤖ᯝ㸪99%
㸦99/100 ࢥࣟࢽ࣮㸧ࡣ blaIMP-6 integron ࢆಖᣢࡋ࡚࠸ࡓࠋblaIMP-6 integron
ࡢᰁⰍయୖ࡬ࡢ⤌ࡳ㎸ࡳࢆᐇドࡍࡿࡓࡵ࡟㸪LTCF ෆ࡛ᝈ⪅ၻ⑱᳨య࠿ࡽศ㞳ࡉࢀࡓ࢝ࣝࣂ࣌ࢿ
࣐࣮ࢮ㠀⏘⏕ P. aeruginosa PC08S㸦ST235㸧࡜ blaIMP-6 ಖ᭷኱⭠⳦ࢆ⏝࠸࡚᥋ྜఏ㐩ᐇ㦂ࢆ⾜
ࡗࡓࠋࡑࡢ⤖ᯝ㸪blaIMP-6 integron ࡣ 2.8™10-7 ࡢ㢖ᗘ࡛᥋ྜఏ㐩ࡋࡓࠋPC08S ᰴ࠾ࡼࡧ PC08S
transconjugant ᰴࡢ blaIMP-6 integron ࡢ࿘㎶ᵓ㐀ࢆゎᯒࡋࡓ⤖ᯝ㸪blaIMP-6 integron ࡢࡳࡀ
PC08S ᰴ ࡢ ᰁ Ⰽ య ୖ ࡟ ⤌ ࡳ ㎸ ࡲ ࢀ ࡚ ࠸ ࡓ ࠋ TC16G ᰴ ࡜ ᐇ 㦂 ⓗ ࡟ స ᡂ ࡋ ࡓ PC08S
transconjugants ᰴࡢࢤࣀ࣒㓄ิẚ㍑ࡢ⤖ᯝ㸪TC16G ᰴ࡜ PC08S ᰴࡣᰁⰍయୖ࡟ྛࠎ஧ࡘࡢ

tnpR㸪tnpA 㓄ิࢆಖ᭷ࡋ㸪PC08S transconjugant ᰴࡣ TC16G ᰴࡢ tnpA ࡜ࡣ␗࡞ࡿ tnpA ࡢ
ୗὶ࡟ᤄධࡉࢀ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ௨ୖࡢࡇ࡜࠿ࡽ blaIMP-6 ࣉࣛࢫ࣑ࢻࡀ㏆␥ᆅ༊ࡢ
ᛴᛶᮇ⑓㝔࠿ࡽᗈᓥ┴ࡢ LTCF ࡢ୰࡟ධࡾ㎸ࡳ㸪blaIMP-6 ಖ᭷ CPO ࡜ࡋ࡚㝔ෆឤᰁࢆ࠾ࡇࡋ㸪
ᝈ⪅⭠⟶ෆ࡛ blaIMP-6 integron ࡀ P. aeruginosa ࡟ఏ㐩ࡉࢀ㸪᪂ࡓ࡞ IMP-6 ⏘⏕ P. aeruginosa
ࢆ⏕ࡳฟࡋࡓࡇ࡜ࡀᙉࡃ♧၀ࡉࢀࡓࠋ