2014~2023年全球国际高危克隆大肠埃希菌ST131的群体遗传特征研究
Global Population Genetic Characterisation of the International High Risk Clone Escherichia coli ST131, 2014~2023
摘要: 背景:国际高危克隆大肠埃希菌(Escherichia coli) ST131是重要的医院获得性病原体,会导致尿路感染,血流感染以及呼吸道感染等,甚至死亡,给全球健康带来重大威胁。目的:探究ST131菌株的群体遗传特征,为控制大肠埃希菌抗生素耐药问题提供更多见解。结果:本研究收集2014~2023年来自全球的7735株ST131菌株全基因组测序数据,对其基因组特征进行了分析发现sul1 (54.6%)、mph(A) (53.3%)、tet(A) (52.5%)、dfrA17 (49.4%)、sul2 (38.4%)、aph(3'')-Ib (38.0%),aph(6)-Id (37.6%),blaTEM-1B (37.2%),blaCTX-M-15 (37.2%)是全球ST131菌株的优势磺胺类、大环内酯类、四环素类、甲氧苄啶类、氨基糖苷类、β-内酰胺类抗生素耐药基因(ARGs)变体。blaCTX-M-27blaNDM-5blaKPC-2blaKPC-3的检出率随时间呈升高趋势;而aac(3)-IIdaac(6')-Ib-crblaOXA-1catB3的检出呈下降趋势;同时aadA5、aph(3'')-Ibaph(6)-IdblaTEM-1BdfrA17、mph(A)、tet(A)的检出呈波动变化(先升高再降低)。O25:H4是ST131的优势血清型。共检出543种毒力基因(VGs),与菌株粘附、定植等功能有关。抗生素耐药基因(ARGs)和毒力基因(VGs)的数量随时间增加而增多(P < 0.01)。结论:ST131大肠埃希菌在全球持续传播,菌株向着高耐药和高毒力的方向进化,正在对临床治疗造成重大威胁。
Abstract: Background: The international high-risk clone Escherichia coli (ST131) is an important hospital-acquired pathogen that causes urinary tract infections, bloodstream infections, and respiratory infections, among other things, and even death, posing a major threat to global health. Objective: To explore the population genetic characteristics of ST131 strains and provide more insights into the problem of controlling antibiotic resistance in Escherichia coli. Results: In this study, we collected whole genome sequencing data of 7735 ST131 strains from around the world from 2014 to 2023 and analysed their genomic characteristics, found that sul1 (54.6%), mph(A) (53.3%), tet(A) (52.5%), dfrA17 (49.4%), sul2 (38.4%), aph(3'')-Ib (38.0%), aph(6)-Id (37.6%), blaTEM-1B (37.2%), blaCTX-M-15 (37.2%) are the dominant antibiotic-resistant gene(ARGs) variants of sulfonamides, macrolides, tetracyclines, mephedrone, aminoglycosides, and β-lactams for the global ST131 strain. blaCTX-M-27, blaNDM-5, blaKPC-2, blaKPC-3 showed an increasing trend in detection over time; while aac(3)-IId, aac(6')-Ib-cr, blaOXA-1, catB3 showed a decreasing trend in detection, while aadA5, aph(3'')-Ib, aph(6)-Id, blaTEM-1B, dfrA17, mph(A), tet(A) were detected with a fluctuating change (increasing and then decreasing). O25:H4 was the dominant serotype of ST131. A total of 543 virulence genes (VGs) were detected, which were related to the functions of strain adhesion and colonisation. The number of ARGs and VGs increased over time (P < 0.01). Conclusion: Escherichia coli ST131 continues to spread globally, with strains evolving towards high drug resistance and virulence and is posing a significant threat to clinical care.
文章引用:李静静. 2014~2023年全球国际高危克隆大肠埃希菌ST131的群体遗传特征研究[J]. 临床医学进展, 2024, 14(12): 527-535. https://doi.org/10.12677/acm.2024.14123113

1. 背景

抗微生物药物耐药性(AMR)被世界卫生组织(WHO)列为全球十大最严重的健康威胁之一(https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019),它被G20峰会(2016年9月,中国杭州)以及联合国大会(2016年9月,美国纽约)定为会议主题[1],这一事实反映了局势的严重性。2019年,全球估计有500万例死亡与AMR感染有关[2],其中95万例死亡归因于大肠埃希菌(Escherichia coli) [3]。大肠埃希菌是最常见的机会性病原体之一,是医院环境中尿路、血液和伤口感染的主要原因[4],其中ST131序列很常见[5],成为了当前备受关注的大肠埃希菌型别之一。

大肠埃希菌ST131是国际高危克隆谱系,也是全球肠外致病性大肠埃希菌(ExPEC)分离株中的主要谱系[6],它属于系统发育组B2 [6],与多重耐药和毒力相关,在过去几十年中急剧传播,在全球广泛流行,并会导致尿路感染,血流感染、呼吸道感染、脓毒血症、败血症、颅内感染等,甚至死亡。例如,莫桑比克某医院从2001年到2014年患有菌血症的儿童血液里收集到的EAEC (肠聚集性大肠埃希菌)中,ST131检出最多,达84.1% [7];在埃及一家医院中收集到的ST131克隆在尿液大肠埃希菌分离株中的检出率达83.4% [8];2017年至2019年在伊朗患有UTI妇女的尿液中检测到的ESBL大肠埃希菌中,55%的分离株为ST131 [9];在日本患有恶性肿瘤的儿童血液里检出的大肠埃希菌中,ST131占41.1% [10];在美国一家医院收集的近20年临床大肠埃希菌样本中,ST131检出率最高,达39% [11];在中国,2018年和2020年从中国15个省市的ICU患者中收集到的CREC分离株中ST131最常见,占30.09% [12];从西班牙12家三级医院的败血症患者血液分离物检出的大肠埃希菌中,ST131占29.7% [13],除了临床环境,ST131在河水[14],蔬菜[15],动物中都有检出。此外,与其他肠外致病性大肠埃希菌(ExPEC)一样,ST131可以无症状地定植于人体肠道,健康人无症状携带ST131的比例甚至达10%左右[16] [17],在到达身体其他部位时可引起有症状的感染,对人体健康带来巨大威胁。

ST131分离株通常表现出多药耐药性,并且经常产生超广谱β-内酰胺酶(ESBL),这使它们能够抵抗许多β-内酰胺类抗生素(包括广谱头孢菌素)的治疗,抗生素耐药性的不断增加使其临床治疗显著复杂化[18]。ST131大肠埃希菌还携带有独特的毒力因子,进一步加重了其致病性,为临床管理带来了更为严重的问题。总之,ST131大肠埃希菌因其全球分布以及与多药耐药性和高毒力的关联而对全球健康造成了重大公共卫生威胁。

鉴于当前ST131菌株的研究多局限于区域性,缺少大规模群体性研究。因此,本研究选取全球ST131菌株全基因组测序(WGS)数据展开分析,阐明近十年ST131菌株基因组抗生素耐药基因(ARGs)的时空分布特征和演变动态和毒力基因(VGs)流行特征,为全球大肠埃希菌耐药防控提供参考,为临床ST131大肠埃希菌用药治疗提供理论依据,为ST131基因组研究提供更多新的见解。

2. 材料与方法

于2024年9月登录Enterobase (https://enterobase.warwick.ac.uk/)数据库收集ST131菌株相关信息。根据菌株分离地点、分离时间信息共下载7735株来自全球2014-2023年的ST131菌株的组装序列(排除分离时间和分为位点未知的菌株)。通过使用血清型查找器SerotypeFinder2.0测定血清型。使用Resfinder2.0筛选ARG,使用VirulenceFinder2.0和VFDB数据库筛选毒力基因,使用数据库PlasmidFinder2.0筛选质粒复制子,使用R4.2.3 maps包绘制世界地图,使用Graphpad Prism9绘制统计图(堆叠图、饼图、条形图、折线图)。

3. 结果

3.1. 菌株基本信息

Figure 1. Global distribution of ST131 strains for the periods 2014~2019 (A) and 2020~2023 (B) (the darker the colour, the higher the number of ST131 strains reported in the corresponding country/region)

1. 2014~2019年(A)和2020~2023年(B)时期ST131菌株的全球分布(颜色越深,相应国家/地区报告的ST131菌株数量就越多)

Figure 2. (A) Detections of ST131 strains on six continents, 2014~2023; (B) Host distribution information for ST131 strains

2. (A) 2014~2023年ST131菌株在六大洲的检出情况;(B) ST131菌株宿主分布信息

本研究一共纳入7735株菌进入分析,其中亚洲2237株,欧洲1513株,非洲74株,大洋洲1200株,北美洲2614株,南美洲97株,主要分布在美国(2114株),日本(1819株)、澳大利亚(969株),加拿大(498株),法国(440株)和英国(322株)。从图1可知,与2014~2019时期相比,2020~2023时期各国菌株数量均呈现减少的趋势,六大洲菌株在2019年达到高峰后检出开始下降,呈现先增加后减少的波动变化(图2(A))。在菌株来源方面(图2(B)),人源菌株最多,6827株,占88%,动物源菌株601株,包括家禽(240)、家畜(60)、伴侣动物(233)、野生动物(64)和水生动物(4),环境源菌株最少,占4% (见图2)。

3.2. 质粒检出情况

Figure 3. Plasmid detection of strain ST131 from 2014~2023

3. 2014~2023年ST131菌株质粒检出情况

本研究一共检出75种质粒型别,IncFIB (AP001918),IncFIA,Col156,IncFII (pRSB107),Col (MG828),IncFII是最常检出的前六种型别(见图3),分别占77.45%,70.36%,66.36%,42.91%,40.44%,33.25%。

3.3. 血清型检出情况

Figure 4. Serotype detection of strain ST131

4. ST131菌株血清型检出情况

本研究一共检出15种血清型,分别为H4,O102:H6,O107/O117:H5,O15:H4,O153:H4,O25:H4等。血清型O25:H4检出率高达75% (见图4),是ST131菌株的优势血清型。

3.4. 抗生素耐药基因(ARGs)的时空分布特征

(A) 氨基糖苷;(B) β-内酰胺;(C) 氯霉素;(D) 甲氧苄啶;(E) 喹诺酮;(F) 大环内酯;(G) 磺胺;(H) 四环素(只有检出数量 ≥ 50的ARGs被纳入了分析)。

Figure 5. Temporal trends in the prevalence of ARGs of strain ST131 from 2014~2023

5. 2014~2023年ST131菌株ARGs流行率的时间变化趋势

本研究发现ST131菌株含有丰富多样的ARGs。在7735株菌株中共检出390种ARGs,从抗生素类别上可分为8类,分别为氨基糖苷类、β-内酰胺类、氯霉素类、甲氧苄啶类、喹诺酮类、大环内酯类、磺胺类以及四环素类(见图5)。其中,磺胺类耐药基因sul1 (54.6%),大环内酯类耐药基因mph(A) (53.3%),四环素类耐药基因(52.5%),甲氧苄啶类耐药基因dfrA17 (49.4%),氨基糖苷类耐药基因aadA5 (48.3%),磺胺类耐药基因sul2 (38.4%),氨基糖苷类耐药基因aph(3'')-Ib(38.0%),aph(6)-Id (37.6%),β-内酰胺耐药基因blaTEM-1B (37.2%),β-内酰胺类耐药基因blaCTX-M-15 (37.2%)是检出率前十位的耐药基因。由图5图6可知:从时间分布上看,β-内酰胺耐药基因blaCTX-M-27 (12.21%~23.51%)、blaNDM-5 (0.16%~4.82%)、blaKPC-2 (0.94%~5.26%)、blaKPC-3 (0%~3.51%),甲氧苄啶类耐药基因dfrA12 (4.38%~7.02%),喹诺酮类耐药基因 qnrS1 (0.94%~7.46%)的检出率呈升高趋势,同时本研究在所有菌株中都检测到了喹诺酮耐药基因gyrA、parC染色体点突变(100%)。而氨基糖苷类耐药基因aac(3)-IId (20.03%~13.16%)、aac(6')-Ib-cr (34.59%~23.16%)、blaOXA-1 (35.05%~23.25%)、catB3 (34.12%~21.49%)的检出呈下降趋势,同时aadA5、aph(3'')-Ib、ph(6)-Id、blaTEM-1BdfrA17、mph(A)、tet(A)的检出呈波动变化(先升高再降低),而耐药基因blaCTX-M-15sul1、sul2的检出率基本保持稳定高检出,而其他的耐药基因比如blaCMY-2blaCTX-M-2等持续低检出。从空间分布上看aadA5、blaCTX-M-15catB3、dfrA17、mph(A)sul1、sul2、tet(A)分别为六大洲的优势氨基糖苷类,ESBL类、氯霉素类、甲氧苄啶类、大环内酯类、磺胺类、四环素类耐药基因优势变体。

Figure 6. Distribution of the number of ARGs (A) and VGs (B) per genome in different sampling cycles (n = 7735)

6. 不同采样周期内每个基因组的ARGs数量(A)和VGs数量(B)分布(n = 7735)

毒力基因在大肠埃希菌与其他脊椎动物宿主的相互作用中起着至关重要的作用。它们被用来确定大肠埃希菌的致病特征,本研究一共检出543种毒力因子,与菌株粘附、定植、抗吞噬、铁摄取和毒素等功能有关。其中如血清抗性基因iss (82.15%),铁摄取基因iucD (89.08%)、iucA (89.54%)、iutA (83.80%)、iucB (89.73%)、ybtA (97.23%)、sitA (97.23%)、irp1 (98.86%)、irp2 (99.57%)、ybtA (99.77%)、fyuA (99.77%)、ompA (99.98%)、ybtQ (99.74%)、ybtX (99.80%),粘附定植相关基因csgD (99.54%)、fimH (99.73%)在菌株中很常见。由图6可知,ARGs和VGs的数量随时间增加而增多,说明菌株向着高耐药和高毒力的方向进化。

4. 讨论

在本研究中,我们报告了ST131大肠埃希菌的高风险克隆菌株的群体遗传特征,该菌株已成为广泛流行的MDR肠外致病性大肠埃希菌菌系,导致全球感染病例不断增加。ST131正在全球蔓延,迫切需要加强监测和采取控制措施来应对这一健康威胁。

近十年在人、动物和环境样本中不断检测到ST131菌株,这意味着各种传播途径可能有助于其传播,再加上不同国家的各种社会经济因素,使得已经达到极限的医疗保健系统成为一个具有挑战性的问题。大肠埃希菌国际高危克隆菌株ST131 AMR的迅速出现,尤其是产ESBL和碳青霉烯酶菌株,将会限制病原体严重感染的治疗选择,已有多个研究证实了ST131感染将导致病人死亡风险增加[19] [20],给临床感染治疗带来了挑战。总的来说,我们的研究发现,在ESBL类耐药基因中,blaCTX-M-15为各大洲优势ESBL耐药基因变体,同时blaCTX-M-27的检出率也在不断升高,先前研究已有类似报告[21] [22]。这与在广谱抗菌选择压力下CTX-M组ESBL基因比TEM和SHV、OXA组ESBL基因更容易传播有关[23]——质粒和整合子等促进了CTX-M基因的有效传播[24] [25]。其次,抗生素的选择加剧促成了这一结果[26],CTX-M的大规模全球传播,被称为“CTX-M大流行”[25],这将对目前严重依赖第三代头孢菌素抑制大肠埃希菌感染的抗菌治疗策略构成威胁。更糟糕的是,我们注意到碳青霉烯类耐药基因在ST131菌株中的检出呈上升趋势,碳青霉烯类抗生素是治疗MDR细菌感染的最后手段[27],产碳青霉烯酶大肠埃希菌在全球的传播是一个重大的世界性公共卫生问题,blaNDM-5对碳青霉烯类和β-内酰胺类抗生素具有广泛的水解性,并具有较高的通过质粒转移的能力。在全球范围内,IncF、IncX3质粒被证明促进了blaNDM-5基因在人和环境中的快速传播[28] [29]。由blaNDM阳性菌株引起的感染与高死亡率和不良预后有关,特别是在新生儿或高危免疫低下患者中[30],一直以来人们都主要关注ESBL类耐药基因在ST131菌株中的高流行,而我们的研究也表明对于碳青霉烯酶类耐药基因在ST131中的检出也应该引起我们的重视。

O25:H4是ST131菌株的优势血清型,与菌株毒力有关[11]。此外,ST131含有丰富多样的毒力基因,可增加菌株致病性,比如fimH,其可介导与尿路上皮蛋白的粘附,是泌尿致病性大肠埃希菌菌株毒力的关键因素,还可通过与PapGII粘附素协同作用在尿路感染中发挥作用[31],同时,fimH介导的细菌侵袭是大肠埃希菌脑膜炎发病机制所必需的[32]。研究已经证明携带含有多种毒力基因(粘附papAkpsM、铁获取iucCiutA)的ST131菌株的血流感染患者的院内死亡率高于非ST131菌株。菌株正在朝着高耐药和高毒力的方向进化,这将使临床治疗复杂化,影响临床治疗效果。

5. 结论

大肠埃希菌ST131正在向着高耐药、高毒力的方向进化,并在人、动物与环境中持续传播,给卫生保健系统带来巨大挑战,加重全球耐药经济负担,迫切需要采取措施遏制其流行和传播。

参考文献

[1] AbuAlshaar, A., Piazza, A., Mercato, A., Marchesini, F., Mattioni Marchetti, V., Bitar, I., et al. (2022) Oxa-244-Producing ST131 Escherichia coli from Surface and Groundwaters of Pavia Urban Area (Po Plain, Northern Italy). Frontiers in Microbiology, 13, Article 920319.
https://doi.org/10.3389/fmicb.2022.920319
[2] Murray, C.J.L., Ikuta, K.S., Sharara, F., Swetschinski, L., Robles Aguilar, G., Gray, A., et al. (2022) Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. The Lancet, 399, 629-655.
https://doi.org/10.1016/s0140-6736(21)02724-0
[3] Naghavi, M., Vollset, S.E., Ikuta, K.S., Swetschinski, L.R., Gray, A.P., Wool, E.E., et al. (2024) Global Burden of Bacterial Antimicrobial Resistance 1990-2021: A Systematic Analysis with Forecasts to 2050. The Lancet, 404, 1199-1226.
https://doi.org/10.1016/s0140-6736(24)01867-1
[4] Xia, C., Yan, R., Liu, C., Zhai, J., Zheng, J., Chen, W., et al. (2024) Epidemiological and Genomic Characteristics of Global blaNDM-Carrying Escherichia coli. Annals of Clinical Microbiology and Antimicrobials, 23, Article No. 58.
https://doi.org/10.1186/s12941-024-00719-x
[5] Downing, T. (2015) Tackling Drug Resistant Infection Outbreaks of Global Pandemic Escherichia coli ST131 Using Evolutionary and Epidemiological Genomics. Microorganisms, 3, 236-267.
https://doi.org/10.3390/microorganisms3020236
[6] Nicolas-Chanoine, M., Bertrand, X. and Madec, J. (2014) Escherichia coli ST131, an Intriguing Clonal Group. Clinical Microbiology Reviews, 27, 543-574.
https://doi.org/10.1128/cmr.00125-13
[7] Mandomando, I., Vubil, D., Boisen, N., Quintó, L., Ruiz, J., Sigaúque, B., et al. (2020) Escherichia coli ST131 Clones Harbouring AggR and AAF/V Fimbriae Causing Bacteremia in Mozambican Children: Emergence of New Variant of fimH27 Subclone. PLOS Neglected Tropical Diseases, 14, e0008274.
https://doi.org/10.1371/journal.pntd.0008274
[8] Abdelrahim, S.S., Fouad, M., Abdallah, N., Ahmed, R.F. and Zaki, S. (2021) Comparative Study of CTX-M-15 Producing Escherichia coli ST131 Clone Isolated from Urinary Tract Infections and Acute Diarrhoea. Infection and Drug Resistance, 14, 4027-4038.
https://doi.org/10.2147/idr.s325669
[9] Rasoulinasab, M., Shahcheraghi, F., Feizabadi, M.M., Nikmanesh, B., Hajihasani, A. and Aslani, M.M. (2021) Distribution of Ciprofloxacin-Resistance Genes among ST131 and Non-St131 Clones of Escherichia coli Isolates with ESBL Phenotypes Isolated from Women with Urinary Tract Infection. Iranian Journal of Microbiology, 13, 294-302.
https://doi.org/10.18502/ijm.v13i3.6389
[10] Hassuna, N.A., Rabea, E.M., Mahdi, W.K.M. and Abdelraheem, W.M. (2024) Biofilm Formation and Antimicrobial Resistance Pattern of Uropathogenic E. coli ST131 Isolated from Children with Malignant Tumors. The Journal of Antibiotics, 77, 324-330.
https://doi.org/10.1038/s41429-024-00704-8
[11] Brumwell, A., Sutton, G., Lantos, P.M., Hoffman, K., Ruffin, F., Brinkac, L., et al. (2023) Escherichia coli ST131 Associated with Increased Mortality in Bloodstream Infections from Urinary Tract Source. Journal of Clinical Microbiology, 61, e0019923.
https://doi.org/10.1128/jcm.00199-23
[12] Zhang, R., Li, Y., Chen, J., Liu, C., Sun, Q., Shu, L., et al. (2023) Population Genomic Analysis Reveals the Emergence of High-Risk Carbapenem-Resistant Escherichia coli among ICU Patients in China. Journal of Infection, 86, 316-328.
https://doi.org/10.1016/j.jinf.2023.02.004
[13] Becerra-Aparicio, F., Gómez-Zorrilla, S., Hernández-García, M., Gijón, D., Siverio, A., Berbel, D., et al. (2023) Significant Increase of CTX-M-15-ST131 and Emergence of CTX-M-27-ST131 Escherichia coli High-Risk Clones Causing Healthcare-Associated Bacteraemia of Urinary Origin in Spain (ITUBRAS-2 Project). Journal of Antimicrobial Chemotherapy, 78, 2291-2296.
https://doi.org/10.1093/jac/dkad234
[14] Biggel, M., Hoehn, S., Frei, A., Dassler, K., Jans, C. and Stephan, R. (2023) Dissemination of ESBL-Producing E. coli ST131 through Wastewater and Environmental Water in Switzerland. Environmental Pollution, 337, Article ID: 122476.
https://doi.org/10.1016/j.envpol.2023.122476
[15] Balbuena-Alonso, M.G., Camps, M., Cortés-Cortés, G., Carreón-León, E.A., Lozano-Zarain, P. and Rocha-Gracia, R.d.C. (2023) Strain Belonging to an Emerging, Virulent Sublineage of ST131 Escherichia coli Isolated in Fresh Spinach, Suggesting That ST131 May Be Transmissible through Agricultural Products. Frontiers in Cellular and Infection Microbiology, 13, Article 1237725.
https://doi.org/10.3389/fcimb.2023.1237725
[16] Kudinha, T. and Kong, F. (2022) Possible Step-Up in Prevalence for Escherichia coli ST131 from Fecal to Clinical Isolates: Inferred Virulence Potential Comparative Studies within Phylogenetic Group B2. Journal of Biomedical Science, 29, Article No. 78.
https://doi.org/10.1186/s12929-022-00862-7
[17] Mohamed, M., Clabots, C., Porter, S.B., Bender, T., Thuras, P. and Johnson, J.R. (2019) Large Fecal Reservoir of Escherichia coli Sequence Type 131-H30 Subclone Strains That Are Shared within Households and Resemble Clinical ST131-H30 Isolates. The Journal of Infectious Diseases, 221, 1659-1668.
https://doi.org/10.1093/infdis/jiz669
[18] Boll, E.J., Overballe-Petersen, S., Hasman, H., Roer, L., Ng, K., Scheutz, F., et al. (2020) Emergence of Enteroaggregative Escherichia coli within the ST131 Lineage as a Cause of Extraintestinal Infections. mBio, 11, e00353-20.
https://doi.org/10.1128/mbio.00353-20
[19] Owens, R.C., Johnson, J.R., Stogsdill, P., Yarmus, L., Lolans, K. and Quinn, J. (2011) Community Transmission in the United States of a CTX-M-15-Producing Sequence Type ST131 Escherichia coli Strain Resulting in Death. Journal of Clinical Microbiology, 49, 3406-3408.
https://doi.org/10.1128/jcm.00993-11
[20] Nejad, M.K., Hasani, A., Soofiyani, S.R., Nahandi, M.Z. and Hasani, A. (2023) Aptitude of Uropathogenic Escherichia coli in Renal Transplant Recipients: A Comprehensive Review on Characteristic Features, and Production of Extended Spectrum β-Lactamase. Current Microbiology, 80, 1369-1469.
https://doi.org/10.1007/s00284-023-03476-w
[21] Matsumura, Y., Johnson, J.R., Yamamoto, M., Nagao, M., Tanaka, M., Takakura, S., et al. (2015) CTX-M-27-and Ctx-M-14-Producing, Ciprofloxacin-Resistant Escherichia coli of the h30 Subclonal Group within ST131 Drive a Japanese Regional ESBL Epidemic. Journal of Antimicrobial Chemotherapy, 70, 1639-1649.
https://doi.org/10.1093/jac/dkv017
[22] Demirci, M., Ünlü, Ö. and İstanbullu Tosun, A. (2019) Detection of O25b-St131 Clone, CTX-M-1 and CTX-M-15 Genes via Real-Time PCR in Escherichia coli Strains in Patients with Utis Obtained from a University Hospital in Istanbul. Journal of Infection and Public Health, 12, 640-644.
https://doi.org/10.1016/j.jiph.2019.02.017
[23] Woerther, P., Burdet, C., Chachaty, E. and Andremont, A. (2013) Trends in Human Fecal Carriage of Extended-Spectrum β-Lactamases in the Community: Toward the Globalization of CTX-M. Clinical Microbiology Reviews, 26, 744-758.
https://doi.org/10.1128/cmr.00023-13
[24] Pitout, J.D.D. and Chen, L. (2023) The Significance of Epidemic Plasmids in the Success of Multidrug-Resistant Drug Pandemic Extraintestinal Pathogenic Escherichia coli. Infectious Diseases and Therapy, 12, 1029-1041.
https://doi.org/10.1007/s40121-023-00791-4
[25] Rossolini, G.M., D’Andrea, M.M. and Mugnaioli, C. (2008) The Spread of CTX-M-Type Extended-Spectrum β-Lactamases. Clinical Microbiology and Infection, 14, 33-41.
https://doi.org/10.1111/j.1469-0691.2007.01867.x
[26] Cantón, R., González-Alba, J.M. and Galán, J.C. (2012) CTX-M Enzymes: Origin and Diffusion. Frontiers in Microbiology, 3, Article 110.
https://doi.org/10.3389/fmicb.2012.00110
[27] Karakonstantis, S., Kritsotakis, E.I. and Gikas, A. (2020) Treatment Options for K. Pneumoniae, P. Aeruginosa and A. Baumannii Co-Resistant to Carbapenems, Aminoglycosides, Polymyxins and Tigecycline: An Approach Based on the Mechanisms of Resistance to Carbapenems. Infection, 48, 835-851.
https://doi.org/10.1007/s15010-020-01520-6
[28] Zou, H., Han, J., Zhao, L., Wang, D., Guan, Y., Wu, T., et al. (2023) The Shared NDM-Positive Strains in the Hospital and Connecting Aquatic Environments. Science of The Total Environment, 860, Article ID: 160404.
https://doi.org/10.1016/j.scitotenv.2022.160404
[29] Wang, D., Berglund, B., Li, Q., Shangguan, X., Li, J., Liu, F., et al. (2023) Transmission of Clones of Carbapenem-Resistant Escherichia coli between a Hospital and an Urban Wastewater Treatment Plant. Environmental Pollution, 336, Article ID: 122455.
https://doi.org/10.1016/j.envpol.2023.122455
[30] Bhattacharjee, A., Sands, K., Mitra, S., Basu, R., Saha, B., Clermont, O., et al. (2023) A Decade-Long Evaluation of Neonatal Septicaemic Escherichia coli: Clonal Lineages, Genomes, and New Delhi Metallo-β-Lactamase Variants. Microbiology Spectrum, 11, e0521522.
https://doi.org/10.1128/spectrum.05215-22
[31] Tseng, C., Lin, W., Wu, A., Wang, M., Teng, C. and Wu, J. (2022) Escherichia coli Fimh Adhesins Act Synergistically with Papgii Adhesins for Enhancing Establishment and Maintenance of Kidney Infection. Journal of Microbiology, Immunology and Infection, 55, 44-50.
https://doi.org/10.1016/j.jmii.2020.09.001
[32] Johnson, J.R., Magistro, G., Clabots, C., Porter, S., Manges, A., Thuras, P., et al. (2018) Contribution of Yersiniabactin to the Virulence of an Escherichia coli Sequence Type 69 (“Clonal Group A”) Cystitis Isolate in Murine Models of Urinary Tract Infection and Sepsis. Microbial Pathogenesis, 120, 128-131.
https://doi.org/10.1016/j.micpath.2018.04.048