Gut reservoir of E. coli ST131

大肠杆菌 ST131 的肠道储存库

• 批准号: 9892970
• 负责人: JAMES R JOHNSON
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892970
• 关键词: Achievement; Address; Animals; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Bacteremia; Bacteroidetes; Behavior; Cells; Cellular Immunity; Characteristics; Ciprofloxacin; Clinical; Data; Development; Ecology; Epidemic; Epidemiology; Escherichia coli; Escherichia coli Infections; Firmicutes; Fluoroquinolones; Funding; Genomics; Half-Life; Health; Health Care Costs; Healthcare; High Prevalence; Household; Human; Immune; Immunologic Factors; Infection; Intervention; Intestines; Investigation; Investments; Laboratories; Lead; Mediating; Modification; Morbidity - disease rate; Mus; Mutation; Nutrient; Nutritional; Operon; Outcome; Personal Communication; Pharmaceutical Preparations; Phenotype; Phylogenetic Analysis; Population; Prevalence; Preventive measure; Probiotics; Proteobacteria; Research; Resistance; Risk Factors; Side; Source; Study models; Testing; Up-Regulation; Urinary tract infection; Vaccines; Veterans; Virulence; Virulent; bacterial community; bacterial genetics; base; burden of illness; cost; epidemiologic data; fitness; fluoroquinolone resistance; genetic element; gut colonization; gut microbiome; gut microbiota; improved; infection burden; member; modifiable risk; mortality; novel; pandemic disease; pathogen; therapy design; trait; transmission process

A new Escherichia coli strain called ST131-H30 – unknown prior to 2000 – is now the single most common cause of E. coli infections such as urinary tract infections, particularly those associated with resistance to first- line antibiotics. Veterans are especially vulnerable to ST131-H30, which causes 25-30% of all their E. coli infections, and 70-75% of those involving fluoroquinolone (e.g., ciprofloxacin) resistance. Gut colonization is an important upstream step in ST131-H30 infections, and therefore is a key part of the ST131-H30 epidemic. We have found that, in veterans and their household members, gut colonization with fluoroquinolone-resistant E. coli (12-13% overall) is quite prolonged (possibly years), is significantly longer for ST131-H30 than other resistant E. coli, and is attributable more to strain persistence than frequent transmission. This suggests the possibility of reducing gut colonization with ST131-H30 by identifying modifiable risk factors, host immune factors, bacterial traits, and characteristics of the gut microbiota that correlate with prolonged H30 colonization and loss of colonization, to inform the development of appropriate interventions. Accordingly, we propose to augment our current longitudinal fecal surveillance of H30-colonized veterans and household members by: · identifying epidemiological risk factors for presence and loss of H30 colonization · identifying humoral and cell-mediated immune correlates of presence and loss of H30 colonization · identifying genomic differences between initial vs. final, and shorter vs. longer-persisting, fecal ST131- H30 isolates · identifying shifts in the gut microbiota (i.e., bacterial community and E. coli population) that correspond with presence and loss of H30 colonization. The results of these studies can be expected to provide essential information needed for the design of interventions (e.g., risk factor modification, vaccines, anti-colonization drugs, and pre- or probiotics) to reduce gut colonization with the ST131-H30 strains that cause infections in veterans. Such interventions should help to reduce the enormous disease burden from infections caused by multi-resistant E. coli, mainly ST131-H30.

一种名为ST 131-H30的新大肠杆菌菌株-在2000年之前未知-现在是最常见的 由于E.大肠杆菌感染，如尿路感染，特别是与耐第一- 线抗生素。退伍军人特别容易感染ST 131-H30，这导致他们所有E。杆菌 感染，和70-75%的涉及氟喹诺酮的那些（例如，环丙沙星）抗性。肠道殖民是一种 在ST 131-H30感染的重要上游步骤，因此是ST 131-H30流行病的关键部分。我们 已经发现，在退伍军人和他们的家庭成员，肠道定植与氟喹诺酮耐药E。 大肠杆菌（总体为12-13%）是相当长的（可能是几年），ST 131-H30比其他 抗性大肠大肠杆菌，并归因于菌株的持久性比频繁的传播。这表明 通过鉴定可改变的风险因素、宿主免疫和/或免疫调节因子， 与H30长期定植相关的因素、细菌性状和肠道微生物群特征 和殖民化的丧失，为制定适当的干预措施提供信息。因此，我们建议 通过以下方式加强我们目前对H30定植退伍军人和家庭成员的纵向粪便监测： ·确定H30定殖存在和丧失的流行病学风险因素 ·鉴定H30定殖的存在和丧失的体液和细胞介导的免疫相关性 ·鉴定初始与最终，以及较短与较长持续时间的粪便ST 131之间的基因组差异- H30分离株 ·识别肠道微生物群的变化（即，细菌群落和E.大肠杆菌群体）， H30定殖的存在和丧失。 这些研究的结果可以预期提供设计所需的基本信息 干预（例如，风险因素修饰、疫苗、抗定植药物和益生菌），以减少 肠道定植ST 131-H30菌株，导致退伍军人感染。这些干预措施应有助于 以减少多重耐药大肠杆菌感染所造成的巨大疾病负担。coli，主要为ST 131-H30。

项目成果

Treatment of ED patients with bacteriuria/pyuria of clinically undetermined significance.

治疗临床意义未确定的菌尿/脓尿 ED 患者。

• DOI: 10.1016/j.ajem.2017.07.057
• 发表时间: 2017
• 期刊: The American journal of emergency medicine
• 作者: Johnson,JamesR

Colonisation with ESBL-producing and carbapenemase-producing Enterobacteriaceae, vancomycin-resistant enterococci, and meticillin-resistant Staphylococcus aureus in a long-term care facility over one year.

• DOI: 10.1186/s12879-015-0880-5
• 发表时间: 2015-04-01
• 期刊: BMC infectious diseases
• 影响因子: 3.7
• 作者: Ludden C;Cormican M;Vellinga A;Johnson JR;Austin B;Morris D
• 通讯作者: Morris D

Horizontally acquired papGII-containing pathogenicity islands underlie the emergence of invasive uropathogenic Escherichia coli lineages.

• DOI: 10.1038/s41467-020-19714-9
• 发表时间: 2020-11-24
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Biggel M;Xavier BB;Johnson JR;Nielsen KL;Frimodt-Møller N;Matheeussen V;Goossens H;Moons P;Van Puyvelde S
• 通讯作者: Van Puyvelde S

Draft genome sequences of concurrent Escherichia coli blood and fecal isolates from a patient with bacteremia and diarrhea belie BioFire-based detection of fecal enteropathogenic E. coli.

从患有菌血症和腹泻的患者身上同时分离出的大肠杆菌血液和粪便的基因组序列草图与基于 BioFire 的粪便肠病性大肠杆菌检测不符。

• DOI: 10.1093/femspd/ftaa058
• 发表时间: 2020
• 期刊: Pathogens and disease
• 影响因子: 3.3
• 作者: Singh,PradipKumar;Johnston,BrianD;Johnson,JamesR;Donnenberg,MichaelS
• 通讯作者: Donnenberg,MichaelS

Bacterial "Virulence" Traits and Host Demographics Predict Escherichia coli Colonization Behaviors Within Households.

• DOI: 10.1093/ofid/ofaa495
• 发表时间: 2020-11
• 期刊: Open forum infectious diseases
• 影响因子: 4.2
• 作者: Fox TC;Clabots C;Porter SB;Bender T;Thuras P;Colpan A;Boettcher J;Johnson JR
• 通讯作者: Johnson JR