표제지
국문요약
목차
용어설명 14
서론 18
연구 대상 및 방법 23
1. 대상 환자 및 균주 23
2. 스트링 테스트 24
3. 전장유전체염기서열 분석 25
1) 핵산추출 25
2) 라이브러리 구축 25
3) 염기서열분석 27
4. 전장 유전체 염기서열 조립 및 해석 29
1) 염기서열단편 조립 29
2) 형별분석 30
3) 항균제 내성 유전자 탐색 31
4) 병독성 인자 탐색 31
5) 플라스미드 시각화 31
5. 임상적 역학 자료 조사 및 통계 36
결과 37
1. 연구대상 환자 및 균주 37
2. 항균제 감수성 검사 및 스트링 테스트 결과 42
3. 전장유전체염기서열 분석결과 44
1) 염기서열단편 조립 44
2) 형별분석 49
3) 항균제 내성 유전자 탐색 65
4) 병독성 인자 탐색 76
4. 연구대상 환자 및 균주 78
1) 대상환자의 임상역학적 분석 78
2) 균주의 분자유전형에 따른 분석 78
3) 단수형 ST307 및 비 ST307형 균주에 대한 분석 79
고찰 83
결론 90
참고문헌 91
Abstract 106
Table 1. Ten public genomes of ST307 CTX-M-15 and/or KPC-2 producing Klebsiella pneumoniae submitted to core-genome multi-locus sequence typing analysis 33
Table 2. Microbiological characteristics of 77 KPC-producing Klebsiella pneumoniae isolates 38
Table 3. Quality control measurements of the assembled contigs of 77 KPC-producing Klebsiella pneumoniae isolates 46
Table 4. Association of sequencing typing and antibiogram among 72 ST307 KPC-producing Klebsiella pneumoniae isolates 53
Table 5. Association of sequencing typing and antibiogram among non-ST307 sequence type KPC-producing Klebsiella pneumoniae isolates 55
Table 6. blaKPC-carrying plasmid and transposon type among ST307 KPC-producing Klebsiella pneumoniae[이미지참조] 59
Table 7. Gene profile of the plasmids from each sequence type of KPC-producing Klebsiellapneumoniae genomes using Prokka 1.14.6 60
Table 8. Antibiogram and resistant determinants of 72 ST307 Klebsiella pneumoniae isolates 69
Table 9. Antibiogram and resistant determinants of non-ST307 sequence type Klebsiella pneumoniae isolates 74
Table 10. Virulence and stress determinants of 77 KPC-producing Klebsiella pneumoniae isolates 77
Table 11. Demographic and clinical features of 77 KPC-producing Klebsiella pneumoniae bacteremia and liver abscess patients 81
Table 12. Comparison of demographic and clinical features between ST307 and non-ST307 KPC-producing Klebsiella pneumoniae patients 82
Figure 1. Batch sequence query webpage for core-genome multi-locus sequence typing 32
Figure 2. Plasmid replicon type query webpage for Enterobacterales 34
Figure 3. Virulence factor query webpage for draft bacterial genomes 35
Figure 4. The isolate of Klebsiella pneumoniae from a case of liver abscess showed a 30mm-extension of a string in a string test 43
Figure 5. Base and read counts of each barcoded genomes. 45
Figure 6. Minimum spanning tree of core-genome multi-locus sequence typing data from 72 ST307 KPC-producing Klebsiella pneumoniae isolates. (A) Four public genomes of ST307... 52
Figure 7. Two plasmids carrying antimicrobial resistance and virulence determinants commonly found in ST307 Klebsiella pneumoniae. ΔTn4401a transposon contained... 56
Figure 8. IncFIB(K)/IncFII plasmid carrying ΔISKpn7-blaKPC-2-ISKpn6 existed alone in ST307 Klebsiella pneumoniae strain 65. This showed mosaicism of IncFIB(K)/IncFII and...[이미지참조] 57
Figure 9. Untypable plasmid carrying ISKpn7-blaKPC-2-ISKpn6 found in ST307 Klebsiella pneumoniae strain 12, 26, and 57.[이미지참조] 58
Figure 10. Two plasmids carrying antimicrobial resistance and virulence determinants found in ST420 Klebsiella pneumoniae. ΔTn4401a transposon comprised ΔISKpn7-blaKPC-₂-...[이미지참조] 64
Figure 11. Molecular typing, resistome and virulome of 72 ST307 KPC-producing K. pneumoniae isolates. Sequence typing by cgMLST wereclustered to the first clone (1), the second clone (2), and singletons (S). 68