學經歷 Education

1997/08-2001/07 Medical Technology, Tzu Chi University, Hualien, Taiwan (B.S.)

慈濟大學 醫事檢驗學系 (學士)

2002/08-2008/10 Institute of Basic Medical Science, Cheng Kung University, Tainan, Taiwan (Ph.D.)

成功大學 基礎醫學研究所 (博士)

Employment Record

2023/08~   Professor

Department of Microbiology and Immunology, Chang Gung University,

Taoyuan, Taiwan

教授 長庚大學 微生物及免疫學科

2018/08-2023/07 Associate Professor

Department of Microbiology and Immunology, Chang Gung University,

Taoyuan, Taiwan

副教授 長庚大學 微生物及免疫學科

2012/08-2017/07 Assistant Professor

Department of Microbiology and Immunology, Chang Gung University,

Taoyuan, Taiwan

助理教授 長庚大學 微生物及免疫學科

2011/11-2012/07 Assistant Professor

Department of Medical Laboratory Science and Biotechnology, Cheng Kung

University, Tainan, Taiwan

助理教授 成功大學 醫學檢驗生物技術學系

2008/12-2011/10 Post doctoral research

Department of Medical Laboratory Science and Biotechnology, Cheng Kung

University, Tainan, Taiwan

博士後研究員 成功大學 醫學檢驗生物技術學系

Research

    Streptococcus pyogenes (group A Streptococcus, GAS) is an important human pathogen

which causes various diseases including pharyngitis, cellulitis, scarlet fever, necrotizing fasciitis, and toxic shock syndrome. Although this pathogen is sensitive to antibiotics treatment, it still causes more than 500,000 deaths per year on the global scale. In addition, no vaccine is available for preventing GAS infections. My research focuses on studying the mechanism of GAS virulence genes regulation under stress conditions by combining bacterial genetics manipulations with different in vitro and in vivo experiment models. In addition, in order to extend the observations of clinical surveillance, the biological significance of GAS phenotypic heterogeneity and instability are studied.

    化膿性鏈球菌 (Streptococcus pyogenes) 是革蘭氏陽性的人類致病菌。常造成細菌性咽喉炎、猩紅熱、以及傷口感染。傷口感染沒有及早就醫，可能會進一步會形成蜂窩性組織炎或是壞死性肌膜炎，由於這些疾病會造成嚴重的肌肉組織壞死，因此這隻細菌有另一個惡名昭彰的名字：噬肉菌。觀測化膿性鏈球菌所造成的感染發現一個非常特別的現像，就是在造成嚴重的感染後，原本的化膿性鏈球菌在動物體內會變成兩種族群，其中一種族群和一開始造成病人感染的細菌有相同的表現型；然而另一種族群則是呈現莢膜大量表現的型態。由於莢膜是細菌造成感染的毒力因子之一，因此，此具有莢膜大量表現的化膿性鏈球菌，和原本的菌株相較，會對實驗動物造成更嚴重的感染疾病。目前的研究已知，這些莢膜大量表現的化膿性鏈球菌

菌株，是因為細菌體中其中一個控制莢膜表現的調控因子發生了突變。在感染的過程，這些發生基因突變的細菌，比沒有發生突變的細菌有更厚的莢膜，所以具有更強的毒性及更好抵抗白血球吞噬的能力。因此，在宿主的體內，原先具有突變的菌株可能只是一個很小的族群，然而，因為白血球等免疫系統的壓力，這個突變的族群就有可能變成主要的族群，之後並更進一步的造成嚴重的感染疾病。

    根據物競天擇 "適者生存，不適者淘汰" 的法則，我們在臨床上應該要看到大多數病人身上所分離出來的化膿性鏈球菌是要有基因突變且具有厚莢膜的表現型。然而，與這個推論相反，大部份所分離到的化膿性鏈球菌菌株，卻都沒有基因突變，且不是有厚莢膜的表現型。為什麼？這些突變的菌株不是毒性比較強嗎？最可能的解釋是，具有基因突變而有厚莢膜表現型的化膿性鏈球菌，可能只有在一個非常特定的環境下有選擇性上的優勢，而在一般的環境，或是在一些比較輕微的感染情況下，其實無法與沒有基因突變的菌株競爭。所以，到底是什麼環境壓力可以選擇出這些毒性較強的菌株？回答這個問題可能可以進一步提供我們發展預防嚴重化膿性鏈球菌感染的策略。

目前實驗室的研究主軸包括：

- 研究此兩種不同表現型的菌株在不同環境壓力下的適應力。

- 研究有基因突變且具有厚莢膜表現型的菌株為何具有較強的毒性。

- 研究相關基因之轉錄調控及訊號傳遞機制。

Publications: 2019-2023 (*: Corresponding author)

Wu HY, Kuo CJ, Chou CH, Ho MW, Chen CL, Hsu TS, Chen YC, Chiang-Ni C, Chen YM, Chiu CH, Lai CH*. 2023. Clostridium innocuum, an emerging pathogen that induces lipid raft-mediated cytotoxicity. Virulence. 14:2265048. https://doi.org/10.1080/21505594.2023.2265048.

Tsai WJ, Lai YH, Shi YA, Hammel M, Duff AP, Whitten AE, Wilde KL, Wu CM, Knott R, Jeng US, Kang CY, Hsu CY, Wu JL, Tsai PJ, Chiang-Ni C, Wu JJ, Lin YS, Liu CC, Senda T, Wang S*. 2023. Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection. Commun Biol. 6:124. https://doi.org/10.1038/s42003-023-04502-0.

Chiang-Ni C*, Chiang CY, Chen YW, Shi YA, Chao YT, Wang S, Tsai PJ, Chiu CH. 2023. RopB-regulated SpeB cysteine protease degrades extracellular vesicles-associated streptolysin O and bacterial proteins from group A Streptococcus. Virulence. 14:2249784. https://doi.org/10.1080/21505594.2023.2249784.

Chiang-Ni C*, Chen YW, Chen KL, Jiang JX, Shi YA, Hsu CY, Chen YM, Lai CH, Chiu CH. 2023. RopB represses the transcription of speB in the absence of SIP in group A Streptococcus. Life Sci Alliance. 6:e202201809. https://doi.org/10.26508/lsa.202201809.

Shi YA, Chen TC, Chen YW, Liu YS, Chen YM, Lai CH, Chiu CH, Chiang-Ni C*. 2022. The bacterial markers of identification of invasive CovR/CovS-inactivated group A Streptococcus. Microbiol Spectr. 10:e0203322. https://doi.org/10.1128/spectrum.02033-22.

Chang CH, Lee SH, Lin YC, Hsu CY, Cheng CC, Teng SH, Chen MF, Hsieh PH, Chang Y, Chiang-Ni C*. 2022. Characterization of the phenotypes of methicillin- and vancomycin-susceptible Staphylococcus argenteus after vancomycin passages. J Glob Antimicrob Resist. 31:63-71. https://doi.org/10.1016/j.jgar.2022.08.006.

Chiang-Ni C*, Liu YS, Lin CY, Hsu CY, Shi YA, Chen YM, Lai CH, Chiu CH. 2021. Incidence and effects of acquisition of the phage-encoded ssa superantigen gene in invasive group A Streptococcus. Front Microbiol. 12:685343. https://doi.org/10.3389/fmicb.2021.685343.

Hsieh CL, Hsieh SY, Huang HM, Lu SL, Omori H, Zheng PX, Ho YN, Cheng YL, Lin YS, Chiang-Ni C, Tsai PJ, Wang SY, Liu CC, Noda T, Wu JJ. 2020. Nicotinamide increases intracellular NAD(+) Content to enhance autophagy-mediated group A streptococcal clearance in endothelial cells. Front Microbiol. 11:117. https://doi.org/10.3389/fmicb.2020.00117.

Chiang-Ni C*, Chiou HJ, Tseng HC, Hsu CY, Chiu CH. 2020. RocA regulates phosphatase activity of virulence sensor CovS of group A Streptococcus in growth phase- and pH-dependent manners. mSphere. 5:e00361-00320. https://doi.org/10.1128/msphere.00361-20.

Chen YW, Huang MZ, Chen CL, Kuo CY, Yang CY, Chiang-Ni C, Chen YM, Hsieh CM, Wu HY, Kuo ML, Chiu CH, Lai CH. 2020. PM2.5 impairs macrophage functions to exacerbate pneumococcus-induced pulmonary pathogenesis. Part Fibre Toxicol. 17:37. https://doi.org/10.1186/s12989-020-00362-2.

Hou TY, Chiang-Ni C, Teng SH. 2019. Current status of MALDI-TOF mass spectrometry in clinical microbiology. J Food Drug Anal. 27:404-414. https://doi.org/10.1016/j.jfda.2019.01.001.

Chiang-Ni C*, Tseng HC, Shi YA, Chiu CH. 2019. Effect of phosphatase activity of the control of virulence sensor (CovS) on clindamycin-mediated streptolysin O production in group A Streptococcus. Infect Immun. 87:e00583-00519. https://doi.org/10.1128/IAI.00583-19.

Chiang-Ni C*, Kao CY, Hsu CY, Chiu CH. 2019. Phosphorylation at the D53 but not the T65 residue of CovR determines the repression of rgg and speB transcription in emm1- and emm49-type group A streptococci. J Bacteriol. 201:e00681-00618. https://doi.org/10.1128/jb.00681-18.

Chen MF, Chang CH, Chiang-Ni C, Hsieh PH, Shih HN, Ueng SWN, Chang Y. 2019. Rapid analysis of bacterial composition in prosthetic joint infection by 16S rRNA metagenomic sequencing. Bone Joint Res. 8:367-377. https://doi.org/10.1302/2046-3758.88.BJR-2019-0003.R2.