Shigella flexneri에 의한 집단발병의 역학적 양상

기현균,김선희,기혜영,서진종,하동룡,김은선,정재근,김성한,이복권 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

배경 : 국내에서 Shigella flexneri에 의한 감염으로 인한 집단발병은 2000년도에 국립보건원에 집단발병례가 보고된 이후 보고되지 않았으나 최근 저자 등은 S. flexneri에 의한 대규모 집단발병을 경험하여 역학적인 양상을 기술하였다. 방법 : OO회사의 직원 및 구내식당을 이용한 사람 및 가족들을 대상으로 증상여부 및 2002년 12월 23일 이후 식당이용 여부와 취식음식에 대하여 설문조사를 실시하였으며 검체를 확보하여 미생물학적 검사를 실시하였다. 결과 : 조사대상 총 258명 중 총 110명에서 증상이 발생하였으며 증상발생일의 분포는 단일정점을 보였다. 확진자는 82명으로 이중 81명은 OO의 식당을 이용한 사람이었고 1명은 식당에서 직접 조리과정에 참여한 사람이었다. 식사여부와 증상여부의 관계를 분석한 결과 특히 24일의 취식여부의 상대위험도가 가장 높았다(RR=6.46, 3.56≤95% CI≤11.75). 항균제 내성 양상은 ampicillin 내성균주가 82균주(100.0%) ampicillin-sulbactam 내성균주가 55균주(67.1%), amoxicillin-clavulanic acid에 대한 내성균주가 62균주(74.4%), trimethoprim-sulfamethoxazole 내성균주가 82균주로 나타났다(98.8%). 분리된 균주간의 연관성을 보기 위하여 실시한 PFGE 결과 본 집단발병에서 확인된 균주는 동일한 양상을 보였으나 비슷한 시기에 분리된 균주와는 서로 다른 양상을 보였다. 결론 : 본 집단발병은 국내에서 발생한 S. flexneri에 의한 집단발병 중 가장 대규모 집단발병이었다. 본 집단발병에서 확인된 균주간의 PFGE양상이 동일하였으나 기존에 국내에서 분리된 균주의 PFGE양상과는 다른 양상을 보였다. 따라서 이러한 상황을 감안한다면 S. flexneri 및 설사환자에 대한 감시체계를 강화해야 할 것이다. Background : Most of the shigellosis outbreak in Korea was caused by Shigella sonnei since late 1990's. In contrast, outbreak by Shigella flexneri were rare since late 1990's. Currently. we experienced the shigellosis outbreak by S. flexneri and described the results of investigation. Methods : We recruited employees from company "A" who had a meal at least once at the company's cafeteria from Dec 23th, 2002 to Dec 26th, 2002. We surveyed the symptoms, food items, and history of travel of eligible persons and their family members. For the microbiological examination, we collected specimen from eligible persons and their family. Collected specimens were cultured for bacteriologic agents and viruses. Epidemiological relationship among the isolates were analyzed by pulsed field gel electrophoresis (PFGE). Results : Among the eligible persons, one hundred ten were symptomatic (110/258, 42,6%). Eighty-two were confirmed bacteriologically. Day of symptom onset showed a unipolar pattern. Diarrhea was the most common symptom among the symptomatic patients (110/110, 100%). The other symptoms included abdominal pain (81.8%), tenesmus (70.0%), headache (63.6%), nausea (61.8%), febrile sense (59.1%), and vomiting (24.5%). Lunch on 24th Dec was the most significant risk factor of the outbreak (RR=6.46, 3.56≤95% Cl≤11.75). All isolates of the outbreak has the same pattern on PFGE analysis and the PFGE pattern was not similar compared with other S. flexneri isolates from Korea. Conclusion : This is the largest and unique outbreak by S.flexneri since 2000 in Korea. The outbreak has the same origin according to the PFGE pattern and epidemic characteristics. Considering rarity of S.flexneri among shigellosis in Korea, surveillance for S.flexneri should be enhanced.

Shigella flexneri infection in a newly acquired rhesus macaque (Macaca mulatta)

Jae-Il Lee,Sang-Joon Kim,Chung-Gyu Park 한국실험동물학회 2011 Laboratory Animal Research Vol.27 No.4

A 3.4 year-old rhesus macaque weighing 4.6 kg, was suffering from anorexia, acute mucous and bloody diarrhea. On physical examination, the monkey showed a loss of activity, hunched posture, abdominal pain, dehydration, mild gingivitis and unclean anus with discharge. Whole blood was collected for the examination of electrolytes, hematology and serum chemistry; fresh stool was also collected for bacterial culture. Blood profiles showed leukocytosis (14.6 K/μL) and neutrophilia (11.0 K/μL) on complete blood cell count and imbalanced electrolytes associated with diarrhea. As a result of bacterial culture, Shigella flexneri was identified through Mac/SS, IMVIC test, TCBS and VITEK II. Based on these results, this monkey was diagnosed as having acute enteritis caused by Shigella flexneri. Treatment was performed with enrofloxacin prior to the isolation of Shigella flexneri to prevent the transmission of disease. Fortunately, mucus and bloody diarrhea did not persist and general conditions fully recovered. Our results show that the use of enrofloxacin is effective in controlling Shigella flexneri infection in newly acquired rhesus monkeys.

A Mouse Model of Shigellosis by Intraperitoneal Infection

Yang, Jin-Young,Lee, Se-Na,Chang, Sun-Young,Ko, Hyun-Jeong,Ryu, Sangryeol,Kweon, Mi-Na Oxford University Press 2014 The Journal of infectious diseases Vol.209 No.2

<P>In human and nonhuman primates, <I>Shigella spp.</I> cause bacillary dysentery by invading colon epithelium and promoting a strong inflammatory response; however, adult mice are resistant to oral <I>Shigella</I> infection. In this study, intraperitoneal challenge with virulent <I>S. flexneri</I> 2a (YSH6000) resulted in diarrhea and severe body weight loss in adult B6 mice. Of note, virulent <I>S. flexneri</I> 2a could invade and colonize not only systemic tissues but also the serosa and lamina propria region of the large intestine. In addition, epithelial shedding, barrier integrity, and goblet cell hyperplasia were found in the large intestine by 24 hours post-intraperitoneal <I>Shigella</I> infection. Of note, predominant expression of proinflammatory cytokines and chemokines were found in the large intestine after intraperitoneal challenge. Monocytes played a critical role in attenuating diarrhea and in providing protective efficacy against intraperitoneal <I>Shigella</I> infection. Most importantly, mice prevaccinated with attenuated <I>S. flexneri</I> 2a (SC602) strain were protected against intraperitoneal challenge with YSH6000. When taken together, these findings show that intraperitoneal challenge with virulent <I>S. flexneri</I> 2a can provoke bacillary dysentery and severe pathogenesis in adult mice. This model may be helpful for understanding the induction mechanism of bacillary dysentery and for evaluating <I>Shigella</I> vaccine candidates.</P>

2005년 농촌 주민들에서 캄보디아와 베트남 여행 중 발생한 세균성이질

임현술(Hyun-Sul Lim),이환석(Hwan-Seok Lee) 한국농촌의학 지역보건학회 2009 농촌의학·지역보건 Vol.34 No.3

농촌 주민들 32명이 캄보디아와 베트남을 여행하였다. 7일간의 여행 중 8명이 설사를 하였다. 이에 원인과 감염경로를 파악하기 위해 역학조사를 시행하였다. 여행자 32명 전원을 대상으로 방문 혹은 전화로 역학조사를 시행하였으며, 23명의 직장도말 검체를 경상북도 보건환경연구원에서 검사하였다. 또한 여행사를 통해 여행 경로와 일정을 조사하였다. 발병률은 25.0%(8명)이었으며, 그 중 3명은 미생물학적으로 Shigella flexneri(Serotype 3a)에 의한 감염을 확인하였다. 외국에서 감염이 발생하였다고 추정하여 환경가검물을 검사할 수 없었지만 공동매개체로는 세균성이질의 잠복기와 역학적 특성을 고려할 때 앙코르와트에서 사 먹은 생수가 세균성이질 균에 오염된 것으로 생각한다. 가장 흔한 해외 유입 전염병은 물이나 음식을 매개로 하는 전염병이다. 외국을 여행하는 여행자들은 수인성/음식매개 감염병에 대하여 철저히 예방을 하고 여행 후 증상이 있는 경우 신고 및 적절한 치료를 받아야 할 것이다. Objectives: A group consisted of 32 Korean rural people had been travelled to Cambodia and Vietnam. During their travel for 7 days, first diarrheal case had occurred on 3rd day of travel and overall 8 people had diarrhea during travel. So we investigated the case for determination of the cause and route of infection. Methods: We interviewed all 32 people by visiting or telephone and took 23 stool samples from them, which are examined by Gyeungsangbuk-do Government Public Institute of Health & Environment in Korea. We interviewed travel agency for travel route and schedule. Results: The attack rate was 25.0% (8 cases) among 32 people. Of them, 3 cases were microbiologically confirmed to have the infection of Shigella flexneri (Serotype 3a). The result of this epidemiological investigation showed that the infection of shigellosis was happened in foreign countries. We assumed the water from Angkor-Watt was contaminated by S. flexneri. We could not able to test environmental specimens because of the infection is thought to be occurred in foreign countries. Conclusions: Most common infectious diseases from foreign countries are transmitted by water or food. Travellers to foreign countries must take caution for communicable diseases and must do report and get appropriate treatment when symptoms developed after travel.

서울지역 설사환자로 부터 분리된 Shigella flexneri의 성상과 유전적 특성

승현정,김무상,오영희,최병현,채희선,초가기,전무형,Seung, Hyun-Jung,Kim, Moo-Sang,Oh, Young-Hee,Choi, Byung-Hyun,Chae, Hee-Sun,Chu, Jiaqi,Jun, Moo-Hyung 대한수의학회 2006 大韓獸醫學會誌 Vol.46 No.4

The shigellae are common etiological agents of bacillary dysentery in humans and primates. During four years from 2002 to 2005, 22 strains of Shigella spp. were isolated from the diarrheic patients in Seoul region. All of them were identified as S. flexneri by biochemical tests and serotyping. The prevalence of serotypes were variable by year, but the major serotypes were 2a and 3a. In an antimicrobial susceptibility test, all of the isolates were resistant to streptomycin and tetracycline, and susceptible to amikacin, kanamycin, cefoxitin, and gentamicin. All of the isolates showed the multi-resistant patterns over 3 drugs. By analysis of the plasmid profile the isolates were classified into 7 groups (P1~P7). Serotypes 2a and 2b were distributed to P1, P2, P3, and P4. Serotype 3a was differentiated to P5 and serotype 3b, to P6 and serotype 4a, to P7. PCR results showed that all isolates were positive for two virulence genes, ipaH and ial, but none of the strains had stx gene. The set1A and set1B genes were detected from 12 isolates (54.5%) that belonged to serotype 2a and 2b. The sen gene was detected from 19 isolates (86.4%). The 22 isolates showed 12 to 17 DNA fragments in the sizes ranging from 20.5 kb to 1135 kb, resulting in 13 patterns by the PFGE with Not I digestion. The PFGE patterns of the isolates showed the close relation with the serotypes, but no relations with year of isolation and antimicrobial resistance.

환아의 혈액과 변에서 분리된 Shigella flexneri의 생화학적 성상, 항균제 감수성 및 Pulsed-Field Gel Electrophoresis 분석

김신무 ( Shin Moo Kim ),임채원 ( Chae Won Lim ),소향아 ( Hyang Ah So ),심은숙 ( Eum Sook Shim ),김은숙 ( Eun Sook Kim ),이규식 ( Kyu Sik Lee ),정윤섭 ( Yunsop Chong ) 대한임상검사과학회 2007 대한임상검사과학회지(KJCLS) Vol.39 No.3

Shigellosis is the most common bacterial gastroenteritis both in developing and developed countries, but bacteremia due to Shigella spp. is very rare. In developed countries recent shigellosis is mostly caused by S. sonnei, but S. flexeri infection is rare. We had rare cases of S. flexeri infections in a family in the Jeonbuk Province: an 8-year-old boy with bacteremic shigellosis and 10- and 12-year-old brothers with diarrhea. The isolates had identical biochemical characteristics, and were resistant to ampicillin, chloramphenicol, and co-trimoxazole. PFGE pattern of NotⅠ-restricted genomic DNA suggested that the isolate from blood was closely related to the two strains isolated from stool which had an identical PFGE pattern.

Proteomic Analysis of Shigella Virulence Effectors Secreted under Different Conditions

( Xingming Liu ),( Lilan Lu ),( Xinrui Liu ),( Xiankai Liu ),( Chao Pan ),( Erling Feng ),( Dongshu Wang ),( Chang Niu ),( Li Zhu ),( Hengliang Wang ) 한국미생물 · 생명공학회 2017 Journal of microbiology and biotechnology Vol.27 No.1

A series of novel effector molecules secreted by the type three secretion system (T3SS) of Shigella spp. have been reported in recent years. In this study, a proteomic approach was applied to study T3SS effectors systematically. First, proteins secreted by the S. flexneri wildtype strain after Congo Red induction were separated and identified using two-dimensional electrophoresis to display the relative abundance of all kinds of early effectors for the first time. Then, a gene deletion mutant of known virulence repressor (OspD1) and a gene overexpressed mutant of two known virulence activators (MxiE and IpgC) were constructed and analyzed to discover potential late effectors. Furthermore, the supernatant proteins of gene deletion mutants of two known translocators (IpaB and IpaD), which would constantly secrete effectors, were also analyzed. Among all of the secreted proteins identified in our study, IpaH1.4, IpaH_5, and IpaH_7 have not been reported before. These proteomics data of the secreted effectors will be valuable to understand the pathogenesis of S. flexneri.

Infection of human intestinal epithelial cells by invasive bacteria activates NF-κB and increases ICAM-1 expression through NOD1

신운건,Bum Joon Park,Sung Joong Lee,Jae Gyu Kim 대한내과학회 2018 The Korean Journal of Internal Medicine Vol.33 No.1

Background/Aims: Nucleotide-binding oligomerization domain 1 (NOD1) is required for primary intestinal epithelial cells (IECs) to respond to natural mucopeptides secreted by gram-negative bacteria. Infection of human IECs with invasive bacteria up-regulates intercellular adhesion molecule-1 (ICAM-1) expression. However, the role of NOD family members in host defense has been largely unknown. The aim of this study was to determine whether there is a functional role for NOD1 in the up-regulation of ICAM-1 expression in invasive bacteria-infected IECs. Methods: ICAM-1 mRNA expression was compared between controls, Caco-2 or HT29 cells transfected with an empty vector, and IECs stably transfected with a dominant-negative (DN) NOD1. Expression was compared using qualitative reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and flow cytometry after infection with enteroinvasive Escherichia coli O29:NM or Shigella flexneri. Nuclear factor kB (NF-κB) activation was determined by electrophoretic mobility shift assays. Results: DN NOD1 significantly inhibited the up-regulation of ICAM-1 expression in response to an enteroinvasive bacterial infection. The Caco-2 cells transfected with DN NOD1 manifested marked inhibition of NF-kB activation in response to E. coli O29:NM infection. Conclusions: Signaling through NOD1 may play an essential role in neutrophil trafficking following infection with enteroinvasive bacteria.

단세포군 항체를 이용한 Shigella serotyping serum 개발(Ⅱ) : S. flexneri type Ⅰ,Ⅱ & type Ⅰ:6, group 6

정의범,이영희,김순남,박강수,이명숙,성원근,김종욱,홍승의,박정우 국립보건연구원 1994 국립보건원보 Vol.31 No.1

Backbone NMR Assignments of an Uncharacterized Protein, SF1002 from Shigella flexneri 5a M90T

이유섭,윤원수,정일,정가영,원형식,서민덕 한국자기공명학회 2015 Journal of the Korean Magnetic Resonance Society Vol.19 No.1

The causative agent of shigellosis, Shigella flexneri, is a Gram-negative anaerobic bacterial pathogen that causes one of the most infectious bacterial dysenteries in humans. It originates infection by invading cells of the colonic epithelium using a type III secretion system. Despite S. flexneri is closely linked with the human disease, structural study is very deficient. Here, we have initiated NMR study of SF1002 which is the uncharacterized protein from S. flexneri strain 5a M90T. Based on a series of triple resonance spectra, sequence-specific assignments of the backbone amide resonances of SF1002 could be completed. This NMR study would contribute to the structural genomics of S.flexneri.