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系統識別號 U0026-0408201507552100
論文名稱(中文) 建立南台灣常見致病菌種達卡產氣單胞菌秀麗隱桿線蟲表皮感染模式
論文名稱(英文) Establish a Caenorhabiditis elegans model of cuticle infection due to Aeromonas dhakensis, a common and virulent Aeromonas species in southern Taiwan
校院名稱 成功大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Institute of Clinical Medicine
學年度 103
學期 2
出版年 104
研究生(中文) 陳柏齡
研究生(英文) Po-Lin Chen
學號 S98981076
學位類別 博士
語文別 英文
論文頁數 109頁
口試委員 指導教授-柯文謙
指導教授-陳昌熙
召集委員-薛博仁
口試委員-蔡佩珍
口試委員-陳彥旭
中文關鍵字 基質輔助雷射脫附游離質譜法  達卡產氣單胞菌  秀麗隱桿線蟲  軟組織感染  p38裂殖原活化蛋白激酶 
英文關鍵字 matrix assisted laser desorption ionization–time of flight mass spectrometry  Aeromonas dhakensis  Caenorhabditis elegans  soft tissue infection  p38 mitogen-activated protein kinase pathway 
學科別分類
中文摘要 背景
大部分人類產氣單胞菌(Aeromonas species)的感染和三種菌種有關,分別是A. hydrophila、 A. veronii 和 A. caviae。許多研究報告指出原先經由表型鑑定為A. hydrophila的分離珠,經由分子方法鑑定後被確認為A. dhakensis,基於下述的理由,我們對於A. dhakensis有著極高的研究興趣:一、以基質輔助雷射脫附游離質譜法(MALDI-TOF MS)鑑定產氣單胞菌的相關研究很少被報告。二、A. dhakensis和其他Aeromonas菌種的人類感染臨床及細菌學特性很少被比較。三、目前A. dhakensis感染的致病機轉還未全然了解。本研究的提出的假設是A. dhakensis是具有高毒性的菌種,可以引起人類嚴重的感染。研究的第一部分我們分析MALDI-TOF MS鑑定臨床Aeromonas臨床菌種的效果,第二部分我們比較了A. dhakensis和其他Aeromonas菌種的血液和傷口分離菌株臨床和生物特性,第三部分我們建立了A. dhakensis在秀麗隱桿線蟲的表皮感染模式,並且用以研究抵抗Aeromoans感染時線蟲表現的p38裂殖原活化蛋白激酶先天免疫系統。
結果
MALDI-TOF鑑定A. dhakensis、A. hydrophila、A. veronii、A. caviae的正確性分別為96.7%、90.0%、96.7%和100%。需要特別強調的是A. dhakensis對於ertapenem和gentamicin的抗藥性分別是12.1%和6.9%。A. dhakensis比A. hydrophila更容易在固體表面形成生物膜(P=0.03)。在液體毒性測試中,線蟲感染A. dhakensis後的三日內存活率都明顯低於A. hydrophila (all P values <0.01)。利用人類皮膚纖維母細胞株測試,結果顯示A. dhakensis的毒性高於A. hydrophila (29.6±1.2% vs. 20.6±0.6%, P<0.0001)。在Aeromonas菌血症病人中,A. dhakensis的敗血症和院內死亡率都高於其他菌種所造成的菌血症(P=0.024 and 0.004, respectively)。
線蟲感染A. dhakensis的三日內存活率明顯低於A. hydrophila、A. veronii和A. caviae (all P values <0.0001)。A. dhakensis對於小鼠C2C12細胞株的毒性明顯高於其他菌種 (all P values <0.0001)。分析細菌毒力因子的結果顯示,33.3%的 A. dhakensis和A. hydrophila菌株帶有ahh1和aerA基因,A. veronii和A. caviae則不帶有ahh1和aerA基因,只有A. veronii帶有aexT基因,A. caviae則不帶有測試的五種毒力因子。在線蟲的感染模式中,細菌侵入並同時在線蟲表皮及肌肉引起壞死性筋膜炎的典型表現,壞死基因asp-3及asp-4的基因表現量感染後會有顯著地上升,而缺乏壞死表現的線蟲突變株vha-12(n2915)感染A. dhakensis AAK1菌株後存活率較野生株N2高,我們用線蟲模型去證明p38裂殖原活化蛋白激酶 (p38 mitogen-activated protein kinase)路徑在感染A. dhakensis後活化,其在皮下及肌肉組織的表現會幫助蟲體抵抗A. dhakensis的感染。
結論
MALDI-TOF MS系統可以快速準確地鑑定Aeromonas菌種,臨床資料分析、生物體外測試及動物實驗暗示不同 Aeromonas菌種間存在著毒性的差異。由於A. dhakensis具有較強的毒性和抗藥性,因此正確地鑑定出此菌種具有重要的臨床價值。秀麗隱桿線蟲可作為研究細菌和宿主在軟組織感染時的模式,探討細菌和宿主參與在此過程的重要因子,這些重要的因子有機會成為將來治療時的新標的。
英文摘要 BACKGROUND:
Most human Aeromonas infections were reported to be associated with three species, i.e., Aeromonas hydrophila, Aeromonas veronii, and Aeromonas caviae. Several studies report that isolates originally identified as A. hydrophila based on phenotypic methods can be recognized as A. dhakensis using molecular typing. Additionally, identification of Aeromonas species using the matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is rarely reported. In human Aeromonas infection, the clinical features and microbiological features of A. dhakensis and other Aeromonas species are rarely being compared. In addition, the host-microbe interaction in Aeromonas infection remains unclear. In the present research, our hypothesis is A. dhakensis is a virulent species, which can cause severe infections in hosts. In the first part of our study, we assessed the performance of MALDI-TOF MS system (Microflex LT; Bruker Daltonik GmbH, Bremen, Germany) to identify the clinical Aeromonas species. Secondly, we compared the clinical and biological features of Aeromonas clinical isolates from human wounds and blood. In the final part, we established A. dhakensis cuticle infection model in Caenorhabditis elegans, and used it to study the innate p38 mitogen-activated protein kinase pathway against Aeromonas infections.
RESULTS:
The accuracy identification rates by MALDI-TOF for A. dhakensis, A. hydrophila, A. veronii, and A. caviae were 96.7%, 90.0%, 96.7%, and 100.0%, respectively. Of note, we highlighted its potential for antimicrobial resistance among A. dhakensis isolates, showing the resistance rates of ertapenem and gentamicin to be 12.1% and 6.9%, respectively. A. dhakensis isolates formed more solid surface-associated biofilms than A. hydrophila isolates (P=0.03). In liquid toxicity assay, the average survival rates of C. elegans infected with A. dhakensis isolates on day 1-3 were significantly lower than those of A. hydrophila isolates (all P values <0.01). In human normal skin fibroblast cell lines, the A. dhakensis isolates exhibited more cytotoxicity than the A. hydrophila isolates (29.6±1.2% vs. 20.6±0.6%, P<0.0001). Among patients with Aeromonas bacteremia, the sepsis-related and in-hospital mortality rates of patients with A. dhakensis bacteremia were significantly higher than those of bacteremia caused by non-dhakensis Aeromonas species (P=0.024 and 0.004, respectively). The survival rates of C. elegans fed with A. dhakensis within the first three days were significantly lower than those with A. hydrophila, A. veronii, and A. caviae (all P values <0.0001). Cytotoxicity assay showed A. dhakensis isolates exhibited more potent cytotoxicity than other species (all P values <0.05) to the C2C12 cell line. In mice infection model, the survival rate for mice infected by A. dhakensis was significantly lower than the other species (all P values <0.0001). Surveying the virulence genes, ahh1 was detected, and aerA in 33.3% of both A. dhakensis and A. hydrophila isolates. ahh1 and aerA were not found in A. veronii and A. caviae. Of note, aexT was only identified in A. veronii isolates and none of A. caviae isolates possessed any of five tested genes. In C. elegans infection model, bacterial invasion and induction of the characteristic lesions of necrotizing soft tissue infection in the cuticle and muscle of C. elegans by A. dhakensis were concomitantly demonstrated in vivo. Relative expression levels of necrosis reporter genes, asp-3 and asp-4 in worms infected by A. dhakensis AAK1 increased significantly. We also assayed the survival of necrosis-deficient C. elegans mutant vha-12(n2915), and showed enhanced survival relative to wild-type N2 worms in infections with A. dhakensis. We used this model to prove the C. elegans p38 mitogen-activated protein kinase pathway is activated and required against A. dhakensis infection in hypodermis and muscle of worms.
CONCLUSION:
The MALDI-TOF MS system can identify Aeromonas species correctly and rapidly. Clinical data, ex vivo experiments, and animal studies suggest there is virulence variation among clinically important Aeromonas species. Correct identification of A. dhakensis among Aeromonas isolates is of clinical value due to its potential virulence and antimicrobial resistance. The C. elegans model has a great potential for the exploration of the important factors of bacteria and innate immunity implicated in severe soft tissue infection. Some of these factors could become targets for the development of new interventions or adjuvant therapies.
論文目次 目錄
ABSTRACT IV
BACKGROUND: IV
RESULTS: IV
CONCLUSION: V
中文摘要 VI
背景 VI
結果 VI
結論 VII
ACKNOWLEDGEMENT VIII
INTRODUCTION 9
MATERIALS AND METHODS 14
SECTION I 14
Bacterial isolates 14
Species identification based on rpoB sequencing, Vitek 2 GN cards and Phoenix system (NMIC/ID-72 cards) (Becton-Dickinson Microbiology Systems) 14
Performance of MALDI Biotyper system 15
SECTION II 15
Species determination of Aeromonas wound isolates 15
Crystal violet biofilm assay 16
Antimicrobial susceptibility tests 16
Liquid toxicity (LT) assay (Caenorhabditis elegans) 16
Cytotoxicity assay 17
PCR detection of the genes encoding putative virulence factors 18
Aeromonas blood isolates 18
Definitions 19
Liquid-toxic (LT) assay of C. elegans infected by aeromonads 20
Life span and pathology of BALB/c mice with Aeromonas intramuscular infection 20
Exoenzyme assay 21
SECTION III 22
C. elegans and bacteria strains 22
Plate assay of Caenorhabditis elegans infected with A. dhakensis AAK1 22
Live C. elegans images 23
Analysis of muscle damage 23
Transmission Electron Microscopy(TEM) and Scanning Electron Microscopy (SEM) study of worms 23
Measurement of asp-3 and asp-4 expression 24
Analysis of activation of the p38 MAPK pathway 24
RNA interference (RNAi) assay 25
RESULTS 26
SECTION I 26
Species identification based on rpoB sequencing, Vitek 2 GN cards and Phoenix system (NMIC/ID-72 cards) (Becton-Dickinson Microbiology Systems) and MALDI-TOF systems 26
Species determination and clinical features of Aeromonas wound isolates 26
Antimicrobial susceptibility tests 27
Crystal violet biofilm assay 27
Liquid toxicity (LT) assay (C. elegans) 28
Cytotoxicity assay 28
PCR detection of the genes encoding putative virulence factors 28
SECTION II 28
Clinical features of patients with septicemia caused by different Aeromonas species 28
Life span of C. elegans infected with different species of Aeromonas 29
Cytotoxicity assay 30
Life spans of BALB/c mice infected by Aeromonas isolates of 4 Aeromonas species 30
Exoenzyme assay 30
Distribution of putative virulence factors among blood isolates of four Aeromonas species 31
SECTION III 31
Aeromonas dhakensis infection shortened life span of C. elegans 31
Morphological change of C. elegans after Aeromonas dhakensis infection 31
Aeromonas dhakensis infection induced expression of necrosis reporter genes asp-3 and asp-4 in C. elegans 32
Necrosis-deficient C. elegans mutants, vha-12(n2915sd) were resistant to Aeromonas dhakensis infection 32
Conserved p38 mitogen-activated protein kinase (MAPK) pathway is required in the innate immunity against A. dhakensis soft tissue infection in C. elegans 33
DISCUSSION 34
SECTION I 34
SECTION II 34
SECTION III 37
CONCLUSION 40
TABLE CONTENT 41
FIGURE CONTENT 42
TABLES 45
FIGURES 50
REFERENCES 79
List of abbreviation 86
APPENDIX 88
參考文獻 1. Hickman-Brenner FW, MacDonald KL, Steigerwalt AG, Fanning GR, Brenner DJ, Farmer JJ, 3rd. Aeromonas veronii, a new ornithine decarboxylase-positive species that may cause diarrhea. J Clin Microbiol. 1987;25:900-6.
2. Wu CJ, Chen PL, Tang HJ, Chen HM, Tseng FC, Shih HI, et al. Incidence of Aeromonas bacteremia in southern Taiwan: Vibrio and Salmonella bacteremia as comparators. J Microbiol Immunol Infect. 2014; 47:145-8.
3. Janda JM, Abbott SL. The genus Aeromonas: taxonomy, pathogenicity, and infection. Clin Microbiol Rev. 2010;23:35-73.
4. Ko WC, Chuang YC. Aeromonas bacteremia: review of 59 episodes. Clin Infect Dis. 1995;20:1298-304.
5. Ko WC, Lee HC, Chuang YC, Liu CC, Wu JJ. Clinical features and therapeutic implications of 104 episodes of monomicrobial Aeromonas bacteraemia. J Infect. 2000;40:267-73.
6. Wu CJ, Wu JJ, Yan JJ, Lee HC, Lee NY, Chang CM, et al. Clinical significance and distribution of putative virulence markers of 116 consecutive clinical Aeromonas isolates in southern Taiwan. J Infect. 2007;54:151-8.
7. Chuang HC, Ho YH, Lay CJ, Wang LS, Tsai YS, Tsai CC. Different clinical characteristics among Aeromonas hydrophila, Aeromonas veronii biovar sobria and Aeromonas caviae monomicrobial bacteremia. J Korean Med Sci. 2011 ;26:1415-20.
8. Chao CM, Gau SJ, Lai CC. Aeromonas genitourinary tract infection. J Infect. 2012;65:573-5.
9. Chao CM, Lai CC, Tang HJ, Ko WC, Hsueh PR. Skin and soft-tissue infections caused by Aeromonas species. Eur J Clin Microbiol Infect Dis. 2012;32:543-7.
10. Chao CM, Lai CC, Tang HJ, Ko WC, Hsueh PR. Biliary tract infections caused by Aeromonas species. Eur J Clin Microbiol Infect Dis. 2013;32:245-51.
11. Chao CM, Lai CC, Tsai HY, Wu CJ, Tang HJ, Ko WC, et al. Pneumonia caused by Aeromonas species in Taiwan, 2004-2011. Eur J Clin Microbiol Infect Dis. 2013;32:1069-75.
12. Tang HJ, Lai CC, Lin HL, Chao CM. Clinical manifestations of bacteremia caused by Aeromonas species in southern Taiwan. PLoS One. 2014;9:e91642.
13. Beaz-Hidalgo MJFaR. Aeromonas: Chapter 4: Aeromonas infections in humans. 2015, Caister Academic Press.
14. Puthucheary SD, Puah SM, Chua KH. Molecular characterization of clinical isolates of Aeromonas species from Malaysia. PLoS One. 2012;7:e30205.
15. Wu CJ, Chen PL, Wu JJ, Yan JJ, Lee CC, Lee HC, et al. Distribution and phenotypic and genotypic detection of a metallo-beta-lactamase, CphA, among bacteraemic Aeromonas isolates. J Med Microbiol. 2012;61(Pt 5):712-9.
16. Chen PL, Wu CJ, Chen CS, Tsai PJ, Tang HJ, Ko WC. A comparative study of clinical Aeromonas dhakensis and Aeromonas hydrophila isolates in southern Taiwan: A. dhakensis is more predominant and virulent. Clin Microbiol Infect. 2014;20:O428-34.
17. Aravena-Roman M, Harnett GB, Riley TV, Inglis TJ, Chang BJ. Aeromonas aquariorum is widely distributed in clinical and environmental specimens and can be misidentified as Aeromonas hydrophila. J Clin Microbiol. 2011;49:3006-8.
18. Figueras MJ, Alperi A, Saavedra MJ, Ko WC, Gonzalo N, Navarro M, et al. Clinical relevance of the recently described species Aeromonas aquariorum. J Clin Microbiol. 2009;47:3742-6.
19. Sanger JR, Yousif NJ, Matloub HS. Aeromonas hydrophila upper extremity infection. J Hand Surg Am. 1989;14:719-21.
20. Voss LM, Rhodes KH, Johnson KA. Musculoskeletal and soft tissue Aeromonas infection: an environmental disease. Mayo Clin Proc. 1992;67:422-7.
21. Gold WL, Salit IE. Aeromonas hydrophila infections of skin and soft tissue: report of 11 cases and review. Clin Infect Dis. 1993;16:69-74.
22. Minnaganti VR, Patel PJ, Iancu D, Schoch PE, Cunha BA. Necrotizing fasciitis caused by Aeromonas hydrophila. Heart Lung. 2000;29:306-8.
23. Moses AE, Leibergal M, Rahav G, Perouansky M, Or R, Shapiro M. Aeromonas hydrophila myonecrosis accompanying mucormycosis five years after bone marrow transplantation. Eur J Clin Microbiol Infect Dis. 1995;14:237-40.
24. Vukmir RB. Aeromonas hydrophila: myofascial necrosis and sepsis. Intensive Care Med. 1992;18:172-4.
25. Lamy B, Laurent F, Kodjo A. Validation of a partial rpoB gene sequence as a tool for phylogenetic identification of aeromonads isolated from environmental sources. Can J Microbiol. 2010;56:217-28.
26. Aguilera-Arreola MG, Hernandez-Rodriguez C, Zuniga G, Figueras MJ, Garduno RA, Castro-Escarpulli G. Virulence potential and genetic diversity of Aeromonas caviae, Aeromonas veronii, and Aeromonas hydrophila clinical isolates from Mexico and Spain: a comparative study. Can J Microbiol. 2007;53:877-87.
27. Morinaga Y, Yanagihara K, Eugenin FL, Beaz-Hidalgo R, Kohno S, Figueras Salvat MJ. Identification error of Aeromonas aquariorum: A causative agent of septicemia. Diagn Microbiol Infect Dis. 2013;76:106-9.
28. Cahill MM. Virulence factors in motile Aeromonas species. J Appl Bacteriol. 1990;69:1-16.
29. Janda JM, Guthertz LS, Kokka RP, Shimada T. Aeromonas species in septicemia: laboratory characteristics and clinical observations. Clin Infect Dis. 1994;19:77-83.
30. Figueras MJ. Clinical relevance of Aeromonas sM503. Reviews in Medical Microbiology. 2005;16:145-53.
31. Martinez-Murcia AJ, Saavedra MJ, Mota VR, Maier T, Stackebrandt E, Cousin S. Aeromonas aquariorum sp. nov., isolated from aquaria of ornamental fish. Int J Syst Evol Microbiol. 200;58(Pt 5):1169-75.
32. Alperi A, Martinez-Murcia AJ, Ko WC, Monera A, Saavedra MJ, Figueras MJ. Aeromonas taiwanensis sp. nov. and Aeromonas sanarellii sp. nov., clinical species from Taiwan. Int J Syst Evol Microbiol. 2010;60(Pt 9):2048-55.
33. Martinez-Murcia AJ, Monera A, Saavedra MJ, Oncina R, Lopez-Alvarez M, Lara E, et al. Multilocus phylogenetic analysis of the genus Aeromonas. Syst Appl Microbiol. 2011;34:189-99.
34. Parker JL, Shaw JG. Aeromonas spp. clinical microbiology and disease. J Infect. 2011;62:109-18.
35. Donohue MJ, Smallwood AW, Pfaller S, Rodgers M, Shoemaker JA. The development of a matrix-assisted laser desorption/ionization mass spectrometry-based method for the protein fingerprinting and identification of Aeromonas species using whole cells. J Microbiol Methods. 2006;65:380-9.
36. Bizzini A, Greub G. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, a revolution in clinical microbial identification. Clin Microbiol Infect. 2010;16:1614-9.
37. Lamy B, Kodjo A, Laurent F. Identification of Aeromonas isolates by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Diagn Microbiol Infect Dis. 2011;71:1-5.
38. Benagli C, Demarta A, Caminada A, Ziegler D, Petrini O, Tonolla M. A rapid MALDI-TOF MS identification database at genospecies level for clinical and environmental Aeromonas strains. PLoS One. 2012;7:e48441.
39. Ermolaeva MA, Schumacher B. Insights from the worm: the C. elegans model for innate immunity. Semin Immunol. 2014;26:303-9.
40. Kim D. Studying host-pathogen interactions and innate immunity in Caenorhabditis elegans. Dis Model Mech. 2008;1:205-8.
41. Marsh EK, May RC. Caenorhabditis elegans, a model organism for investigating immunity. Appl Environ Microbiol. 2012;78:2075-81.
42. Zhang Y, Li W, Li L, Li Y, Fu R, Zhu Y, et al. Structural Damage in the C. elegans epidermis causes release of STA-2 and induction of an innate immune response. Immunity. 2015;42:309-20.
43. Ziegler K, Kurz CL, Cypowyj S, Couillault C, Pophillat M, Pujol N, et al. Antifungal innate immunity in C. elegans: PKC-delta links G protein signaling and a conserved p38 MAPK cascade. Cell Host Microbe. 2009;5:341-52.
44. Zugasti O, Bose N, Squiban B, Belougne J, Kurz CL, Schroeder FC, et al. Activation of a G protein-coupled receptor by its endogenous ligand triggers the innate immune response of Caenorhabditis elegans. Nat Immunol. 2014;15:833-8.
45. Corsi AK, Wightman B, Chalfie M. A Transparent window into biology: A Primer on Caenorhabditis elegans. Genetics. 2015;200:387-407.
46. Hakkarainen TW, Kopari NM, Pham TN, Evans HL. Necrotizing soft tissue infections: review and current concepts in treatment, systems of care, and outcomes. Curr Probl Surg. 2014;51:344-62.
47. Syntichaki P, Xu K, Driscoll M, Tavernarakis N. Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature. 2002 31;419:939-44.
48. Wong D, Bazopoulou D, Pujol N, Tavernarakis N, Ewbank JJ. Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection. Genome Biol. 2007;R194.
49. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22:240-73.
50. Chen GY, Nunez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol. 2010;10:826-37.
51. Jansson HB. Adhesion of conidia of Drechmeria coniospora to Caenorhabditis elegans wild type and mutants. J Nematol. 1994;26:430-5.
52. Pujol N, Cypowyj S, Ziegler K, Millet A, Astrain A, Goncharov A, et al. Distinct innate immune responses to infection and wounding in the C. elegans epidermis. Curr Biol. 2008;18:481-9.
53. Couillault C, Pujol N, Reboul J, Sabatier L, Guichou JF, Kohara Y, et al. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nat Immunol. 2004;5:488-94.
54. Dierking K, Polanowska J, Omi S, Engelmann I, Gut M, Lembo F, et al. Unusual regulation of a STAT protein by an SLC6 family transporter in C. elegans epidermal innate immunity. Cell Host Microbe. 2011;9:425-35.
55. Beaz-Hidalgo R, Martinez-Murcia A, Figueras MJ. Reclassification of Aeromonas hydrophila subsp. dhakensis Huys et al. 2002 and Aeromonas aquariorum Martinez-Murcia et al. 2008 as Aeromonas dhakensis sp. nov. comb nov. and emendation of the species Aeromonas hydrophila. Syst Appl Microbiol. 2013;36:171-6.
56. Soler L, Yanez MA, Chacon MR, Aguilera-Arreola MG, Catalan V, Figueras MJ, et al. Phylogenetic analysis of the genus Aeromonas based on two housekeeping genes. Int J Syst Evol Microbiol. 2004;54(Pt 5):1511-9.
57. Tang HJ, Chen CC, Cheng KC, Toh HS, Su BA, Chiang SR, et al. In vitro efficacy of fosfomycin-containing regimens against methicillin-resistant Staphylococcus aureus in biofilms. J Antimicrob Chemother. 2012;67:944-50.
58. Clinical Laboratory Standard Institution. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline-Second Edition. Wayne, PA: CLSI; 2010. Clinical and Laboratory Standards Institute (CLSI) M45-A2.
59. Martino ME, Fasolato L, Montemurro F, Rosteghin M, Manfrin A, Patarnello T, et al. Determination of microbial diversity of Aeromonas strains on the basis of multilocus sequence typing, phenotype, and presence of putative virulence genes. Appl Environ Microbiol. 2011;77:4986-5000.
60. Rimola A, Garcia-Tsao G, Navasa M, Piddock LJ, Planas R, Bernard B, et al. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. International Ascites Club. J Hepatol. 2000;32:142-53.
61. Lee NY, Lee CC, Huang WH, Tsui KC, Hsueh PR, Ko WC. Carbapenem therapy for bacteremia due to extended-spectrum-beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae: implications of ertapenem susceptibility. Antimicrob Agents Chemother. 2012;56:2888-93.
62. Chow JW, Yu VL. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents. 1999 ;11:7-12.
63. Chen PL, Chang CM, Wu CJ, Ko NY, Lee NY, Lee HC, et al. Extraintestinal focal infections in adults with nontyphoid Salmonella bacteraemia: predisposing factors and clinical outcome. J Intern Med. 2007;261:91-100.
64. Emekdas G, Aslan G, Tezcan S, Serin MS, Yildiz C, Ozturhan H, et al. Detection of the frequency, antimicrobial susceptibility, and genotypic discrimination of Aeromonas strains isolated from municipally treated tap water samples by cultivation and AP-PCR. Int J Food Microbiol. 2006;107:310-4.
65. Daly KA, Wolf M, Johnson SA, Badylak SF. A rabbit model of peripheral compartment syndrome with associated rhabdomyolysis and a regenerative medicine approach for treatment. Tissue Eng Part C Methods. 2011;17:631-40.
66. Qadota H, Inoue M, Hikita T, Koppen M, Hardin JD, Amano M, et al. Establishment of a tissue-specific RNAi system in C. elegans. Gene. 2007;400:166-73.
67. Yigit E, Batista PJ, Bei Y, Pang KM, Chen CC, Tolia NH, et al. Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. Cell. 2006;127:747-57.
68. Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, et al. Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature. 2002;419:808-14.
69. Wu CJ, Wang HC, Chen CS, Shu HY, Kao AW, Chen PL, et al. Genome sequence of a novel human pathogen, Aeromonas aquariorum. J Bacteriol. 2012;194:4114-5.
70. Chen PL, Wu CJ, Chen CS, Tsai PJ, Tang HJ, Ko WC. A comparative study of clinical Aeromonas dhakensis and Aeromonas hydrophila isolates in southern Taiwan: A. dhakensis is more predominant and virulent. Clin Microbiol Infect. 2014;20:O428-34.
71. Chen CS, Bellier A, Kao CY, Yang YL, Chen HD, Los FC, et al. WWP-1 is a novel modulator of the DAF-2 insulin-like signaling network involved in pore-forming toxin cellular defenses in Caenorhabditis elegans. PLoS One. 2010;5:e9494.
72. Chou TC, Chiu HC, Kuo CJ, Wu CM, Syu WJ, Chiu WT, et al. Enterohaemorrhagic Escherichia coli O157:H7 Shiga-like toxin 1 is required for full pathogenicity and activation of the p38 mitogen-activated protein kinase pathway in Caenorhabditis elegans. Cell Microbiol. 2013;15:82-97.
73. Vaglio P, Lamesch P, Reboul J, Rual JF, Martinez M, Hill D, et al. WorfDB: the Caenorhabditis elegans ORFeome Database. Nucleic Acids Res. 2003;31:237-40.
74. Syntichaki P, Samara C, Tavernarakis N. The vacuolar H+ -ATPase mediates intracellular acidification required for neurodegeneration in C. elegans. Curr Biol. 2005;15:1249-54.
75. Irazoqui JE, Urbach JM, Ausubel FM. Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol. 2010;10:47-58.
76. Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, et al. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science. 2002;297:623-6.
77. Lamy B, Laurent F, Verdier I, Decousser JW, Lecaillon E, Marchandin H, et al. Accuracy of 6 commercial systems for identifying clinical Aeromonas isolates. Diagn Microbiol Infect Dis. 2010;67:9-14.
78. Chen PL, Ko WC, Wu CJ. Complexity of beta-lactamases among clinical Aeromonas isolates and its clinical implications. J Microbiol Immunol Infect. 2012;45:398-403.
79. Wu CJ, Wang HC, Chen PL, Chang MC, Sunny Sun H, Chou PH, et al. AQU-1, a chromosomal class C beta-lactamase, among clinical Aeromonas dhakensis isolates: Distribution and clinical significance. Int J Antimicrob Agents. 2013;42:456-61.
80. Esteve C, Alcaide E, Blasco MD. Aeromonas hydrophila subsp. dhakensis isolated from feces, water and fish in Mediterranean Spain. Microbes Environ. 2012;27:367-73.
81. Kozlova EV, Popov VL, Sha J, Foltz SM, Erova TE, Agar SL, et al. Mutation in the S-ribosylhomocysteinase (luxS) gene involved in quorum sensing affects biofilm formation and virulence in a clinical isolate of Aeromonas hydrophila. Microb Pathog. 2008;45:343-54.
82. Couillault C, Ewbank JJ. Diverse bacteria are pathogens of Caenorhabditis elegans. Infect Immun. 2002;70:4705-7.
83. Gravato-Nobre MJ, Hodgkin J. Caenorhabditis elegans as a model for innate immunity to pathogens. Cell Microbiol. 2005;7:741-51.
84. Bogaerts A, Temmerman L, Boerjan B, Husson SJ, Schoofs L, Verleyen P. A differential proteomics study of Caenorhabditis elegans infected with Aeromonas hydrophila. Dev Comp Immunol. 2010;34:690-8.
85. Chopra AK, Houston CW, Peterson JW, Jin GF. Cloning, expression, and sequence analysis of a cytolytic enterotoxin gene from Aeromonas hydrophila. Can J Microbiol. 1993;39:513-23.
86. Yu HB, Rao PS, Lee HC, Vilches S, Merino S, Tomas JM, et al. A type III secretion system is required for Aeromonas hydrophila AH-1 pathogenesis. Infect Immun. 2004;72:1248-56.
87. Albert MJ, Ansaruzzaman M, Talukder KA, Chopra AK, Kuhn I, Rahman M, et al. Prevalence of enterotoxin genes in Aeromonas spp. isolated from children with diarrhea, healthy controls, and the environment. J Clin Microbiol. 2000 ;38:3785-90.
88. Wang G, Clark CG, Liu C, Pucknell C, Munro CK, Kruk TM, et al. Detection and characterization of the hemolysin genes in Aeromonas hydrophila and Aeromonas sobria by multiplex PCR. J Clin Microbiol. 2003;41:1048-54.
89. Chakraborty T, Huhle B, Hof H, Bergbauer H, Goebel W. Marker exchange mutagenesis of the aerolysin determinant in Aeromonas hydrophila demonstrates the role of aerolysin in A. hydrophila-associated systemic infections. Infect Immun. 1987;55:2274-80.
90. Wong CY, Heuzenroeder MW, Flower RL. Inactivation of two haemolytic toxin genes in Aeromonas hydrophila attenuates virulence in a suckling mouse model. Microbiology. 1998;144:291-8.
91. Heuzenroeder MW, Wong CY, Flower RL. Distribution of two hemolytic toxin genes in clinical and environmental isolates of Aeromonas spp.: correlation with virulence in a suckling mouse model. FEMS Microbiol Lett. 1999;174:131-6.
92. Santos JA, Gonzalez CJ, Otero A, Garcia-Lopez ML. Hemolytic activity and siderophore production in different Aeromonas species isolated from fish. Appl Environ Microbiol. 1999;65:5612-4.
93. Osman K, Aly M, Kheader A, Mabrok K. Molecular detection of the Aeromonas virulence aerolysin gene in retail meats from different animal sources in Egypt. World J Microbiol Biotechnol. 2012;28:1863-70.
94. Yi SW, You MJ, Cho HS, Lee CS, Kwon JK, Shin GW. Molecular characterization of Aeromonas species isolated from farmed eels (Anguilla japonica). Vet Microbiol. 2013 May 31;164(1-2):195-200.
95. Lee CC, Chi CH, Lee NY, Lee HC, Chen CL, Chen PL, et al. Necrotizing fasciitis in patients with liver cirrhosis: predominance of monomicrobial Gram-negative bacillary infections. Diagn Microbiol Infect Dis. 2008;62:219-25.
96. Chao CM, Lai CC, Gau SJ, Hsueh PR. Skin and soft tissue infection caused by Aeromonas species in cancer patients. J Microbiol Immunol Infect. 2013;46:144-6.
97. Papadakis V, Poniros N, Katsibardi K, Charissiadou AE, Anastasopoulos J, Polychronopoulou S. Fulminant Aeromonas hydrophila infection during acute lymphoblastic leukemia treatment. J Microbiol Immunol Infect. 2012;45:154-7.
98. Grim CJ, Kozlova EV, Ponnusamy D, Fitts EC, Sha J, Kirtley ML, et al. Functional genomic characterization of virulence factors from necrotizing fasciitis-causing strains of Aeromonas hydrophila. Appl Environ Microbiol. 2014 15;80:4162-83.
99. Kelly KA, Koehler JM, Ashdown LR. Spectrum of extraintestinal disease due to Aeromonas species in tropical Queensland, Australia. Clin Infect Dis. 1993;16:574-9.
100. Borger van der Burg BL, Bronkhorst MW, Pahlplatz PV. Aeromonas hydrophila necrotizing fasciitis. A case report. J Bone Joint Surg Am. 2006;88:1357-60.
101. Kihiczak GG, Schwartz RA, Kapila R. Necrotizing fasciitis: a deadly infection. J Eur Acad Dermatol Venereol. 2006;20:365-9.
102. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg. 1995;221:558-63.
103. Tan MW, Mahajan-Miklos S, Ausubel FM. Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci U S A. 1999;96:715-20.
104. Chen PL, Wu CJ, Tsai PJ, Tang HJ, Chuang YC, Lee NY, et al. Virulence diversity among bacteremic Aeromonas isolates: Ex Vivo, animal, and clinical evidences. PLoS One. 2014;9:e111213.
105. Alvarado-Kristensson M, Melander F, Leandersson K, Ronnstrand L, Wernstedt C, Andersson T. p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human neutrophils. J Exp Med. 2004;199:449-58.
106. Hu M, Du Q, Vancurova I, Lin X, Miller EJ, Simms HH, et al. Proapoptotic effect of curcumin on human neutrophils: activation of the p38 mitogen-activated protein kinase pathway. Crit Care Med. 2005;33:2571-8.
107. Ipaktchi K, Mattar A, Niederbichler AD, Hoesel LM, Vollmannshauser S, Hemmila MR, et al. Attenuating burn wound inflammatory signaling reduces systemic inflammation and acute lung injury. J Immunol. 2006;177:8065-71.
108. Ipaktchi K, Mattar A, Niederbichler AD, Hoesel LM, Vollmannshauser S, Hemmila MR, et al. Topical p38 MAPK inhibition reduces bacterial growth in an in vivo burn wound model. Surgery. 2007;142:86-93.
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