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RAPID INCREASE IN ANTIBODIES TO INFLUENZA A VIRUS H5 and N1 IN LESSER SCAUP (AYTHYA AFFINIS) FOLLOWING THE INTRODUCTION OF 2.3.4.4B H5N1 INTO NORTH AMERICA. 在北美引入2.3.4.4B型H5N1病毒后,在较小的猪瘟中,对甲型流感病毒H5和N1的抗体迅速增加。
IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-13 DOI: 10.1139/cjm-2025-0176
Jeffery Sullivan, Rebecca Poulson, Glenn H Olsen, Alicia M Berlin, Zijing Cao, Deborah L Carter, Josh Homyack, Jennifer Kilburn, Scott Mcwilliams, Joshua Osborn, Tori Mezebish Quinn, Hannah L Schley, Matthew Weegman, Christopher K Williams, David E Stallknecht, Diann J Prosser

Clade 2.3.4.4b Eurasian-origin H5N1 entered North America in late 2021 and spread across the continent. While studies have characterized the antibody response mounted by dabbling ducks following exposure, little data are available for diving ducks. This study sought to identify influenza A virus (IAV) infection and antibodies in Lesser and Greater Scaup captured in Maryland, Illinois, and Rhode Island. In Maryland, IAV seroprevalence increased from the 2021/2022 to 2022/2023 sampling season, with IAV antibody prevalence increasing for juvenile (38% to 80%) and adult (82% to 90%) Lesser Scaup. While adult Lesser Scaup sampled in Illinois in 2021/2022 had IAV antibody prevalence comparable to those sampled in Maryland (76% and 82%, respectively), they had higher antibody prevalence to both H5 (48% and 18%) and N1 (68% and 35%), potentially due to being sampled in March versus December and January. Our data suggest that Lesser Scaup had limited antibodies to highly pathogenic H5 IAV prior to the introduction of clade 2.3.4.4b H5N1 to North America, but relevant antibodies were widely observed in the months and year following. Our more limited data suggest similar trends may have occurred in Greater Scaup as well.

来自欧亚的H5N1进化枝2.3.4.4b于2021年底进入北美并在整个大陆传播。虽然有研究描述了涉水鸭在接触后产生的抗体反应,但潜水鸭的数据很少。本研究旨在确定在马里兰州、伊利诺伊州和罗德岛州捕获的小流感病毒(IAV)感染和抗体。在马里兰州,从2021/2022年到2022/2023年的采样季节,IAV抗体阳性率有所上升,其中青少年(38%至80%)和成人(82%至90%)的IAV抗体阳性率有所上升。虽然2021/2022年在伊利诺伊州采样的成年小鳞鼻虫的IAV抗体患病率与在马里兰州采样的成年人相当(分别为76%和82%),但他们对H5(48%和18%)和N1(68%和35%)的抗体患病率更高,可能是由于在3月采样而不是12月和1月。我们的数据表明,在将H5N1进化枝2.3.4.4b引入北美之前,Lesser scup对高致病性H5 IAV的抗体有限,但在随后的几个月和一年中,相关抗体被广泛观察到。我们更有限的数据表明,类似的趋势也可能发生在Greater scup地区。
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引用次数: 0
Examining the Competitive Exclusion and Pathogenic Potential of Pseudomonadota Isolated from Healthy Chickens. 健康鸡假单胞菌竞争排斥及其致病潜力的研究。
IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-07 DOI: 10.1139/cjm-2025-0179
Zhixuan Feng, Jennifer Ronholm

The chicken intestine presents a complex environment for microbial survival due to high interbacterial competition, high bile salt concentrations, a low pH, and microaerophilic conditions. While most probiotics contain members of the Bacillota phylum, members of the Pseudomonadota phylum are known to be more important in competitive exclusion - which may be an important consideration in the formulation of future probiotics. Little is known about commensal Pseudomonadota in healthy chickens, or what benefits members of this phylum may offer the host; most studies on Pseudomonadota focus on aspects of opportunistic pathogenesis and dysbiosis. In this study, we use an in-silico approach to evaluate the pathogenic potential, competition strategies, and potential host benefits of Pseudomonadota isolates from healthy chickens. We analyzed the draft genomes of 29 representative isolates of Pseudomonadota using Bagle4, AntiSMash, SeCreT6, KEGG mapper, and Virsorter2 to identify key interbacterial competition strategies including secondary metabolite biosynthesis, secretion systems, quorum sensing, and prophages. Our results revealed that each isolate exhibits distinct interbacterial competitive strategies, often independent of their taxonomic affiliation. Including Pseudomonadota in future poultry probiotics may be critical to improving colonization resistance in industrially raised poultry.

鸡肠由于细菌间竞争激烈、胆汁盐浓度高、pH值低和嗜微气条件,呈现出复杂的微生物生存环境。虽然大多数益生菌都含有杆菌门的成员,但假单胞菌门的成员在竞争性排斥中更为重要-这可能是未来益生菌配方中的一个重要考虑因素。人们对健康鸡的共生假单胞菌知之甚少,也不知道这个门的成员可能给宿主带来什么好处;大多数关于假单胞菌的研究都集中在机会发病机制和生态失调方面。在这项研究中,我们使用计算机方法来评估从健康鸡中分离的假单胞菌的致病潜力、竞争策略和潜在的宿主效益。我们使用Bagle4、AntiSMash、SeCreT6、KEGG mapper和Virsorter2分析了29株假单胞菌的代表性分离株的基因组草案,以确定主要的细菌间竞争策略,包括次级代谢物生物合成、分泌系统、群体感应和噬菌体。我们的研究结果表明,每个分离株都表现出不同的细菌间竞争策略,通常独立于它们的分类隶属关系。在未来的家禽益生菌中加入假单胞菌可能对提高工业化饲养家禽的定植抗性至关重要。
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引用次数: 0
Interactions between common scab-inducing strains on potato suberin. 马铃薯单宁上常见疮痂诱导菌株之间的相互作用。
IF 1.8 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1139/cjm-2024-0242
Mario Khalil, Iauhenia Isayenka, Rebeca Padilla-Reynaud, Sylvain Lerat, Carole Beaulieu

Potato tuber periderm is armored with suberin, that consists of two domains, an aliphatic domain composed of fatty acid polyesters and an aromatic domain composed of cinnamic acids. Streptomyces scabies 87.22, a predominant causal agent of potato common scab, was compared for adaptation to tuber suberin with Streptomyces acidiscabies ATCC 49003 and Streptomyces turgidiscabies Car8 belonging to emerging pathogenic species. Streptomyces scabies 87.22 showed higher growth in the suberin supplemented medium than the two other strains. When co-cultured in a rich nutrient medium, S. acidiscabies ATCC 49003 produced the antibiotic oxanthromicin, which inhibited growth and mycelium development of the other strains. Exposure of S. scabies 87.22 and S. acidiscabies ATCC 49003 to suberin was accompanied by the secretion of enzymes degrading cellulose, hemicellulose, fatty acids, and glycerol derivatives. Compared to the two other strains, S. scabies 87.22 showed higher esterase activity in suberin-supplemented medium and strong induction of cellulase gene expression. Both S. acidiscabies ATCC 49003 and S. turgidiscabies Car8 exhibited a poor utilization of trans-ferulic and p-coumaric acids, suggesting almost no ability to degrade the aromatic moiety of suberin. This work suggests that S. scabies 87.22 is better adapted to the potato periderm degradation than the emerging pathogens. The elucidation of pathogenic Streptomyces strains interaction may contribute to the improvement of ecologically oriented agronomic strategies for common scab management.

马铃薯块茎的外皮有一层由两个结构域组成的铠甲--由脂肪酸聚酯组成的脂肪结构域和由肉桂酸组成的芳香结构域。疮痂病链霉菌 87.22 是马铃薯普通疮痂病的主要病原菌,它与酸性链霉菌 ATCC 49003 和瘤胃链霉菌 Car8 都属于新出现的致病菌种,两者对块茎小体蛋白的适应性进行了比较。疥疮链霉菌 87.22 在补充了小瘤脂的培养基中的生长速度高于其他两种菌株。在富营养培养基上共培养时,疮痂病菌 ATCC 49003 产生了抗生素 oxanthromicin,它抑制了其他菌株的生长和菌丝发育。S. scabies 87.22 和 S. acidiscabies ATCC 49003 与单宁接触时会分泌降解纤维素、半纤维素、脂肪酸和甘油衍生物的酶。与其他两株菌株相比,疥疮杆菌 87.22 在添加了单宁的培养基中表现出更高的酯酶活性,并能强烈诱导纤维素酶基因的表达。S. acidiscabies ATCC 49003 和 S. turgidiscabies Car8 对反式阿魏酸和对香豆酸的利用率都很低,这表明它们几乎没有降解单宁酸芳香分子的能力。这项工作表明,与新出现的病原体相比,疥疮杆菌 87.22 更适应马铃薯表皮的降解。阐明致病链霉菌株之间的相互作用可能有助于改进以生态为导向的常见疮痂病管理农艺策略。
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引用次数: 0
Correction: Characterization and whole-genome sequencing of an extreme arsenic tolerant Citrobacter freundii SRS1 strain isolated from Savar area in Bangladesh. 更正:从孟加拉国Savar地区分离的一种极端耐砷弗氏柠檬酸杆菌SRS1菌株的鉴定和全基因组测序。
IF 1.8 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1139/cjm-2024-0195
Mohammed Jafar Uddin, Farhana Haque, Ishrat Jabeen, Sabbir R Shuvo
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引用次数: 0
Candida albicans: a historical overview of investigations into an important human pathogen. 白色念珠菌:一种重要的人类病原体调查的历史概况。
IF 1.8 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1139/cjm-2025-0036
Manjari Shrivastava, Malcolm Whiteway

In recent decades, the study of the opportunistic pathogenic fungus, Candida albicans, has been revolutionized by genomics, transforming our understanding of its molecular biology, pathogenicity, and modes of drug resistance. In this review, our effort is to trace the historical development of C. albicans research, from early clinical observations to modern high-throughput genomic techniques. Advances in molecular biology, transcriptomics, and genome editing, including CRISPR-Cas9, have had a significant impact on the genetic tools available for studying this pathogen. The impact of whole-genome sequencing, functional genomics, and single-cell transcriptomics on the study of C. albicans, alongside the role of fungal population genomics in tracking evolutionary adaptations, have resulted in key insights. Here we discuss the ongoing challenge of antifungal resistance and the implications of new technologies in combating invasive candidiasis. As we move into a new era of precision mycology, integrating multi-omics approaches will further enhance our ability to understand and control C. albicans infections.

近几十年来,对机会致病性真菌白色念珠菌的研究已经通过基因组学发生了革命性的变化,改变了我们对其分子生物学、致病性和耐药模式的理解。在这篇综述中,我们的努力是追溯白色念珠菌研究的历史发展,从早期临床观察到现代高通量基因组技术。包括CRISPR-Cas9在内的分子生物学、转录组学和基因组编辑技术的进步,对研究这种病原体的遗传工具产生了重大影响。全基因组测序、功能基因组学和单细胞转录组学对白色念珠菌研究的影响,以及真菌种群基因组学在追踪进化适应方面的作用,已经产生了关键的见解。在这里,我们讨论抗真菌耐药性的持续挑战和新技术在对抗侵袭性念珠菌病的意义。随着我们进入精确真菌学的新时代,整合多组学方法将进一步提高我们理解和控制白色念珠菌感染的能力。
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引用次数: 0
Development and evaluation of a sensitive approach for detection and recovery of third-generation cephalosporin- and carbapenem-resistant Enterobacterales from ready-to-eat frozen stone fruit. 开发和评估从即食冷冻核果中检测和回收耐第三代头孢菌素和碳青霉烯类肠杆菌的灵敏方法。
IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1139/cjm-2024-0210
Adeeb Nasta, Ashley L Cooper, Irelynd V Tackabury, Chloe Anastasiadis, Calvin Ho-Fung Lau, Liam P Brown, Myron L Smith, Sandeep Tamber, Catherine D Carrillo

Antimicrobial resistance (AMR) is a global public health threat, but the role of foods in its dissemination is poorly understood. We examined the incidence of foodborne bacteria carrying AMR genes considered high-priority research targets by the World Health Organization. Frozen, ready-to-eat, avocado, coconut, mango, and peach (n = 161) were tested for bacteria encoding extended-spectrum β-lactamases (ESBLs) and carbapenemases. Over 600 presumptive-positive isolates were recovered and analyzed with a pooled sequencing (Pool-seq) strategy. Coconut samples exhibited the highest bacterial loads and prevalence/diversity of AMR genes. Isolates harbouring the β-lactamase genes blactx-m, blatem, and blashv, identified in 14 coconut and 2 mango samples, were further characterized by whole-genome sequencing and antimicrobial susceptibility testing. The most common gene was blactx-m-15, detected in 20 unique strains. Two carbapenemase-producing strains were isolated from coconut: Enterobacter roggenkampii encoding blandm-1 and Escherichia coli encoding blandm-5. Subsequent quantitative PCR (qPCR) analysis of enrichments for blactx-m/blandm indicated a potentially higher prevalence of these genes than observed by colony screening. This study presents a practical method for recovering ESBL- and carbapenemase-producing bacteria from foods. Mapping their distribution in food products is crucial to assessing the role of foods in the global spread of AMR and developing effective public health interventions.

抗微生物药物耐药性(AMR)是一个全球性的公共卫生威胁,但人们对食物在其传播中的作用知之甚少。我们检查了携带AMR基因的食源性细菌的发生率,这些基因被世界卫生组织视为高度优先的研究目标。对冷冻、即食、鳄梨、椰子、芒果和桃子(n=161)进行了编码广谱β-内酰胺酶(ESBLs)和碳青霉烯酶的细菌检测。超过600个推定阳性分离株被回收并使用池测序策略(Pool-seq)进行分析。椰子样品显示出最高的细菌载量和AMR基因的患病率/多样性。从14份椰子和2份芒果样品中分离出含有β-内酰胺酶基因blaCTX-M、blaTEM和blaSHV的分离株,并通过全基因组测序和抗菌药敏试验对其进行了进一步鉴定。最常见的基因是blaCTX-M-15,在20个独特的菌株中检测到。从椰子中分离到两株产碳青霉烯酶的菌株:编码blaNDM-1的罗根坎皮肠杆菌和编码blaNDM-5的大肠杆菌。随后对blaCTX-M/blaNDM基因的qPCR富集分析表明,这些基因的流行率可能高于菌落筛选。本研究提出了一种从食品中回收产生ESBL和碳青霉烯酶的细菌的实用方法。绘制它们在食品中的分布地图,对于评估食品在抗菌素耐药性全球传播中的作用和制定有效的公共卫生干预措施至关重要。
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引用次数: 0
Machine learning methods to identify markers and predict antimicrobial resistance in Escherichia coli. 机器学习方法在大肠杆菌中识别标记物和预测抗菌素耐药性。
IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1139/cjm-2024-0208
Janice Moat, Athanasios Zovoilis, Rylan Steinkey, Rahat Zaheer, Tim McAllister, Chad Laing

Antimicrobial resistant strains of pathogenic Escherichia coli are a burden on the healthcare system, causing longer hospital stays and increased treatment costs compared to nonresistant strains. With whole genome sequencing almost ubiquitous in the analyses of outbreak and surveillance samples, in silico methods for feature identification can be faster and cheaper than traditional wet-lab methods. In this study, machine learning (ML) classification methods were used to predict antimicrobial resistance (AMR) and identify novel genomic markers of resistance. A total of 4300 E. coli whole genome sequences with laboratory-derived susceptible, intermediate, or resistant (SIR) data for 34 antimicrobials were collected. Three models-gradient boosted decision trees, support vector machines (SVMs), and artificial neural networks (ANNs)-were trained using genome subsequences (k-mers) of length 11 to classify unknown isolates as SIR for each antimicrobial. The models achieved high average accuracies (93.6%, 92.7%, and 92.8%, respectively) for our dataset, outperforming database methods including AMRFinderPlus (63.9%) and ResFinder (75.7%). Tested on two smaller independent datasets, the models' average accuracies were 81.6% (XGB), 79.9% (SVM), and 81.2% (ANN), while ResFinder's average accuracy was 94.7%. An advantage of ML models over database methods is that they can identify novel markers of resistance, which is a key advantage for surveillance and research. As more genomic and AMR data become publicly available, these models are expected to further improve in performance and utility.

致病性大肠杆菌耐药菌株是卫生保健系统的负担,与非耐药菌株相比,导致住院时间更长,治疗费用增加。随着全基因组测序在疫情暴发和监测样本分析中几乎无处不在,用于特征识别的计算机方法可以比传统的湿实验室方法更快、更便宜。在这项研究中,机器学习(ML)分类方法被用于预测抗菌素耐药性和鉴定新的耐药性基因组标记。共收集了4300份大肠杆菌全基因组序列,其中包含34种抗菌素的实验室衍生敏感、中间或耐药(SIR)数据。使用长度为11的基因组亚序列(k-mers)训练梯度增强决策树、支持向量机和人工神经网络三种模型,将每种抗菌素的未知分离物分类为SIR。对于我们的数据集,模型的平均准确率分别为93.6%、92.7%和92.8%,优于AMRFinderPlus(63.9%)和ResFinder(75.7%)等数据库方法。在两个较小的独立数据集上进行测试,模型的平均准确率为81.6% (XGB), 79.9% (SVM)和81.2% (ANN),而ResFinder的平均准确率为94.7%。ML模型相对于数据库方法的一个优势是,它们可以识别新的耐药性标记,这是监测和研究的一个关键优势。随着更多基因组和抗菌素耐药性(AMR)数据的公开,这些模型有望进一步提高性能和实用性。
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引用次数: 0
A pilot study on the effects of in-feed probiotic Lactobacillus rhamnosus ATCC 53103 (LGG) on vaccinated Atlantic salmon (Salmo salar): microbiomes and Aeromonas salmonicida challenge resilience. 饲料中添加鼠李糖乳杆菌ATCC 53103 (LGG)对接种大西洋鲑鱼(Salmo salar)微生物组和杀沙门氏气单胞菌抗性影响的初步研究
IF 1.8 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-01-17 DOI: 10.1139/cjm-2024-0130
Natalia Lorenc, Steven Leadbeater, Josh Wang, Jennifer Ronholm, Xiaoji Liu

The use of probiotics is an alternative approach to mitigate the proliferation of antimicrobial resistance in aquaculture. In our study, we examined the effects of Lactobacillus rhamnosus GG (ATCC 53103, LGG) delivered in-feed on the weight, length, skin mucus, and faecal microbiomes of Atlantic salmon. We also challenged the salmon with Aeromonas salmonicida 2004-05MF26 (Asal2004) and assessed the mortality. Our results showed no significant change (P > 0.05) in weight or length of Atlantic salmon or their resilience to Asal2004 infection after LGG feeding. Infection changed significantly the skin mucus and faecal microbiomes: Clostridium sensu stricto increased from 3.14% to 9.20% in skin mucus and 1.39% to 3.74% in faeces (P < 0.05). Aeromonas increased from 0.02% to 0.60% in faeces (P < 0.05). Photobacterium increased from not detected (0%) to 52.16% (P < 0.01) and Aliivibrio decreased from 67.21% to 0.71% in faeces (P < 0.01). After infection, Lactococcus (9.93%) and Lactobacillus (2.11%) in skin mucus of the LGG group were significantly higher (P < 0.05) than in the skin mucus from the rest of the groups (4.14% and 1.08%, respectively). In conclusion, LGG feeding did not further increase the resilience of vaccinated Atlantic salmon. Asal2004 infection had much greater impact on skin mucus and faecal microbiomes than LGG feeding.

使用益生菌是减轻水产养殖中抗菌素耐药性扩散的另一种方法。在我们的研究中,我们检测了饲料中添加鼠李糖乳杆菌GG (ATCC 53103, LGG)对大西洋鲑鱼体重、长度、皮肤粘液和粪便微生物群的影响。用沙门氏气单胞菌2004-05MF26 (Asal2004)攻毒鲑鱼,并对其死亡率进行了评估。结果表明,饲喂LGG后,大西洋鲑鱼的体重、体长及对Asal2004感染的抵抗力均无显著变化(P < 0.05)。感染显著改变了皮肤粘液和粪便微生物群:皮肤粘液中的严格感梭菌从3.14%增加到9.20%,粪便中的1.39%增加到3.74%(气单胞菌P从0.02%增加到0.60%),光杆菌P从未检出(0%)增加到52.16%(粪弧菌P从67.21%下降到0.71%),皮肤粘液中的乳球菌P(9.93%)和乳酸菌P(2.11%)在LGG组显著升高(P
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引用次数: 0
Variation in plasmid conjugation among nontyphoidal Salmonella enterica serovars. 非伤寒沙门氏菌血清型质粒结合的变异。
IF 1.8 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2024-12-18 DOI: 10.1139/cjm-2024-0164
Anna Laidlaw, Madeleine Blondin-Brosseau, Julie A Shay, Forest Dussault, Mary Rao, Nicholas Petronella, Sandeep Tamber

Conjugation is a complex phenomenon involving multiple plasmid, bacterial, and environmental factors. Here we describe an IncI1 plasmid encoding multidrug antibiotic resistance to aminoglycosides, sulfonamides, and third-generation cephalosporins. This plasmid is widespread geographically among animal, human, and environmental sectors. We present data on the transmissibility of this plasmid from Salmonella enterica ser. Kentucky into 40 strains of S. enterica (10 strains each from serovars Enteritidis, Heidelberg, Infantis, and Typhimurium). Thirty seven out of 40 strains were able to take up the plasmid. Rates of conjugation were variable between strains ranging from 10-8 to 10-4. Overall, serovars Enteritidis and Typhimurium demonstrated the highest rates of conjugation, followed by Heidelberg, and then Infantis. No relationships were observed between the recipient cell surface and rate of conjugation. Recipient cell numbers correlated positively with conjugation rate and strains with high conjugation rates had marginally but significantly higher growth parameters compared to strains that took up the plasmid at lower frequencies. Environmental conditions known to impact cell growth, such as temperature, nutrient availability, and the presence of antibiotics, had a modulating effect on conjugation. Collectively, these results will further understanding of plasmid transmission dynamics in Salmonella, which is a critical first step towards the development of mitigation strategies.

偶联是一个涉及多种质粒、细菌和环境因素的复杂现象。在这里,我们描述了一个IncI1质粒编码对氨基糖苷类、磺胺类和第三代头孢菌素具有多药耐药性。该质粒在地理上广泛存在,并在同一卫生组织的动物、人类和环境部门中广泛存在。我们提出了该质粒在大肠杆菌中传播的数据。从肯塔基州分离出40株肠球菌(分别来自肠炎、海德堡肠炎、婴儿肠炎和鼠伤寒各10株)。40个菌株中有37个能够吸收质粒。接合率在菌株之间变化,范围从10^-8到10^-4。总体而言,肠炎和鼠伤寒血清型显示出最高的结合率,其次是海德堡,然后是婴儿。受体细胞表面与偶联率之间没有关系。受体细胞数与偶联率呈正相关,偶联率高的菌株的生长参数略高于频率较低的菌株。已知影响细胞生长的环境条件,如温度、营养物质的可用性和抗生素的存在,对偶联具有调节作用。总的来说,这些结果将进一步了解沙门氏菌的质粒传播动力学,这是制定缓解策略的关键的第一步。
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引用次数: 0
Engineering conjugative plasmids for inducible horizontal DNA transfer. 用于诱导水平DNA转移的工程共轭质粒。
IF 1.8 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1139/cjm-2024-0241
Tahani Jaafar, Emily Carvalhais, Arina Shrestha, Ryan R Cochrane, Jordyn S Meaney, Stephanie L Brumwell, Samir Hamadache, Vida Nasrollahi, Bogumil J Karas

Rapidly developing microbial resistance to existing antimicrobials poses a growing threat to public health and global food security. Current chemical-based treatments target cells by inhibiting growth or metabolic function, but their effectiveness is diminishing. To address the growing antimicrobial resistance crisis, there is an urgent need for innovative therapies. Conjugative plasmids, a natural mechanism of horizontal gene transfer in bacteria, have been repurposed to deliver toxic genetic cargo to recipient cells, showing promise as next-generation antimicrobial agents. However, the ecological risks posed by unintended gene transfer require robust biocontainment strategies. In this study, we developed inducible conjugative plasmids to solve these challenges. Utilizing an arabinose-inducible promoter, we evaluated 13 plasmids with single essential gene deletions, identifying trbC and trbF as strong candidates for stringent regulation. These plasmids demonstrated inducibility in both cis and trans configurations, with induction resulting in up to a 5-log increase in conjugation efficiency compared to uninduced conditions. Although challenges such as reduced conjugation efficiency and promoter leakiness persist, this work establishes a foundation for the controlled transfer of plasmids, paving the way for safer and more effective antimicrobial technologies.

微生物对现有抗菌素迅速产生耐药性,对公共卫生和全球粮食安全构成越来越大的威胁。目前基于化学的治疗通过抑制细胞生长或代谢功能来靶向细胞,但其效果正在减弱。为了解决日益严重的抗微生物药物耐药性危机,迫切需要创新疗法。共轭质粒是细菌中水平基因转移的一种自然机制,已被重新用于向受体细胞传递有毒的遗传货物,显示出作为下一代抗菌剂的前景。然而,意外基因转移带来的生态风险需要强有力的生物控制策略。在这项研究中,我们开发了可诱导的共轭质粒来解决这些挑战。利用阿拉伯糖诱导启动子,我们评估了13个具有单个必需基因缺失的质粒,确定了trbC和trbF作为严格调控的强有力候选。这些质粒在顺式和反式结构中都具有诱导性,与未诱导的条件相比,诱导导致的共轭效率提高了5倍。尽管偶联效率降低和启动子泄漏等挑战仍然存在,但这项工作为控制质粒转移奠定了基础,为更安全和更有效的抗菌技术铺平了道路。
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Canadian journal of microbiology
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