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Emerging strategies to target virulence in Pseudomonas aeruginosa respiratory infections. 针对铜绿假单胞菌呼吸道感染毒力的新策略。
IF 6 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-01 Epub Date: 2023-11-24 DOI: 10.1080/1040841X.2023.2285995
Tegan M Hibbert, Marvin Whiteley, Stephen A Renshaw, Daniel R Neill, Joanne L Fothergill

Pseudomonas aeruginosa is an opportunistic pathogen that is responsible for infections in people living with chronic respiratory conditions, such as cystic fibrosis (CF) and non-CF bronchiectasis (NCFB). Traditionally, in people with chronic respiratory disorders, P. aeruginosa infection has been managed with a combination of inhaled and intravenous antibiotic therapies. However, due in part to the prolonged use of antibiotics in these people, the emergence of multi-drug resistant P. aeruginosa strains is a growing concern. The development of anti-virulence therapeutics may provide a new means of treating P. aeruginosa lung infections whilst also combatting the AMR crisis, as these agents are presumed to exert reduced pressure for the emergence of drug resistance as compared to antibiotics. However, the pipeline for developing anti-virulence therapeutics is poorly defined, and it is currently unclear as to whether in vivo and in vitro models effectively replicate the complex pulmonary environment sufficiently to enable development and testing of such therapies for future clinical use. Here, we discuss potential targets for P. aeruginosa anti-virulence therapeutics and the effectiveness of the current models used to study them. Focus is given to the difficulty of replicating the virulence gene expression patterns of P. aeruginosa in the CF and NCFB lung under laboratory conditions and to the challenges this poses for anti-virulence therapeutic development.

铜绿假单胞菌是一种机会性病原体,可引起慢性呼吸系统疾病患者的感染,如囊性纤维化(CF)和非CF性支气管扩张(NCFB)。传统上,在慢性呼吸系统疾病患者中,铜绿假单胞菌感染是通过吸入和静脉注射抗生素联合治疗来控制的。然而,部分由于这些人长期使用抗生素,多重耐药铜绿假单胞菌菌株的出现日益引起人们的关注。抗毒力疗法的发展可能为治疗铜绿假单胞菌肺部感染提供一种新的手段,同时也可以对抗抗生素耐药性危机,因为与抗生素相比,这些药物被认为对耐药性的出现施加了更小的压力。然而,开发抗毒疗法的管道定义不明确,目前尚不清楚体内和体外模型是否有效地复制了复杂的肺部环境,从而能够开发和测试未来临床使用的此类疗法。在这里,我们讨论了铜绿假单胞菌抗毒治疗的潜在靶点以及目前用于研究它们的模型的有效性。重点是在实验室条件下在CF和NCFB肺中复制铜绿假单胞菌毒力基因表达模式的困难,以及这对抗毒力治疗开发带来的挑战。
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引用次数: 0
Review on computer-assisted biosynthetic capacities elucidation to assess metabolic interactions and communication within microbial communities. 综述计算机辅助生物合成能力阐释,以评估微生物群落内的代谢相互作用和交流。
IF 6 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-01-25 DOI: 10.1080/1040841X.2024.2306465
Mahnoor Zulfiqar, Vinay Singh, Christoph Steinbeck, Maria Sorokina

Microbial communities thrive through interactions and communication, which are challenging to study as most microorganisms are not cultivable. To address this challenge, researchers focus on the extracellular space where communication events occur. Exometabolomics and interactome analysis provide insights into the molecules involved in communication and the dynamics of their interactions. Advances in sequencing technologies and computational methods enable the reconstruction of taxonomic and functional profiles of microbial communities using high-throughput multi-omics data. Network-based approaches, including community flux balance analysis, aim to model molecular interactions within and between communities. Despite these advances, challenges remain in computer-assisted biosynthetic capacities elucidation, requiring continued innovation and collaboration among diverse scientists. This review provides insights into the current state and future directions of computer-assisted biosynthetic capacities elucidation in studying microbial communities.

微生物群落通过相互作用和交流而茁壮成长,但由于大多数微生物无法培养,因此研究工作具有挑战性。为了应对这一挑战,研究人员将重点放在发生交流活动的细胞外空间。细胞外代谢组学和相互作用组分析有助于深入了解参与交流的分子及其相互作用的动态。测序技术和计算方法的进步使得利用高通量多组学数据重建微生物群落的分类和功能概况成为可能。基于网络的方法,包括群落通量平衡分析,旨在模拟群落内部和群落之间的分子相互作用。尽管取得了这些进展,但计算机辅助生物合成能力阐释仍面临挑战,需要不同科学家之间的持续创新与合作。本综述深入探讨了计算机辅助生物合成能力阐释在微生物群落研究中的现状和未来发展方向。
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引用次数: 0
Mycobacteroides abscessus ability to interact with the host mucosal cells plays an important role in pathogenesis of the infection. 脓肿分枝杆菌与宿主粘膜细胞相互作用的能力在感染的发病机制中起着重要作用。
IF 6 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.1080/1040841X.2024.2418130
Amy Leestemaker-Palmer, Luiz E Bermudez

Non-tuberculous mycobacteria (NTM) are opportunistic pathogens ubiquitous in the environment. Mycobacteroides abscessus is a relatively new pathogen associated with underlying lung chronic pathologies, accounting for most of the pulmonary infections linked to the rapidly growing mycobacteria group. This includes chronic obstructive pulmonary disease, bronchiectasis, or cystic fibrosis. Patient outcomes from M. abscessus infections are poor due to complicated treatments and other factors. Intrinsic drug resistance plays an important role. The M. abscessus toolbox of resistance is varied leading to complex strategies for treatment. Mechanisms include waxy cell walls, drug export mechanisms, and acquired resistance. Many studies have also shown the impact of extracellular DNA found in the biofilm matrix during early infection and its possible advantage in pathogenicity. In this review, we discuss the current knowledge of early infection focusing on biofilm formation, an environmental strategy, and which treatments prevent its formation improving current antibiotic treatment outcomes in preliminary studies.

非结核分枝杆菌(NTM)是一种机会性病原体,在环境中无处不在。脓肿分枝杆菌是一种相对较新的病原体,与潜在的肺部慢性病变有关,在与快速增长的分枝杆菌群相关的肺部感染中占大多数。这包括慢性阻塞性肺病、支气管扩张或囊性纤维化。由于治疗复杂和其他因素,脓毒症分枝杆菌感染患者的预后很差。内在耐药性起着重要作用。脓肿霉菌的抗药性工具箱多种多样,导致治疗策略复杂。其机制包括蜡质细胞壁、药物输出机制和获得性抗药性。许多研究还显示了在早期感染期间生物膜基质中发现的细胞外 DNA 的影响及其在致病性方面可能具有的优势。在这篇综述中,我们将讨论目前关于早期感染的知识,重点是生物膜的形成(一种环境策略),以及哪些治疗方法可以阻止生物膜的形成,从而在初步研究中改善目前的抗生素治疗效果。
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引用次数: 0
Anti-fungal peptides: an emerging category with enthralling therapeutic prospects in the treatment of candidiasis. 抗真菌肽:在治疗念珠菌病方面具有令人着迷的治疗前景的新兴类别。
IF 6 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-23 DOI: 10.1080/1040841X.2024.2418125
Jyoti Sankar Prusty, Ashwini Kumar, Awanish Kumar

Candida infections, particularly invasive candidiasis, pose a serious global health threat. Candida albicans is the most prevalent species causing candidiasis, and resistance to key antifungal drugs, such as azoles, echinocandins, polyenes, and fluoropyrimidines, has emerged. This growing multidrug resistance (MDR) complicates treatment options, highlighting the need for novel therapeutic approaches. Antifungal peptides (AFPs) are gaining recognition for their potential as new antifungal agents due to their diverse structures and functions. These natural or recombinant peptides can effectively target fungal virulence and viability, making them promising candidates for future antifungal development. This review examines infections caused by Candida species, the limitations of current antifungal treatments, and the therapeutic potential of AFPs. It emphasizes the importance of identifying novel AFP targets and their production for advancing treatment strategies. By discussing the therapeutic development of AFPs, the review aims to draw researchers' attention to this promising field. The integration of knowledge about AFPs could pave the way for novel antifungal agents with broad-spectrum activity, reduced toxicity, targeted action, and mechanisms that limit resistance in pathogenic fungi, offering significant advancements in antifungal therapeutics.

念珠菌感染,尤其是侵袭性念珠菌病,对全球健康构成严重威胁。白色念珠菌是引起念珠菌病最普遍的菌种,对唑类、棘白菌素类、多烯类和氟嘧啶类等主要抗真菌药物的耐药性已经出现。这种日益增长的多药耐药性(MDR)使治疗方案变得更加复杂,凸显了对新型治疗方法的需求。抗真菌肽(AFPs)因其多样的结构和功能,作为新型抗真菌剂的潜力正日益得到认可。这些天然肽或重组肽能有效针对真菌的毒力和存活能力,使它们成为未来抗真菌开发的候选药物。本综述探讨了念珠菌引起的感染、目前抗真菌治疗的局限性以及 AFPs 的治疗潜力。它强调了确定新型 AFP 靶点及其生产对于推进治疗策略的重要性。通过讨论 AFPs 的治疗发展,该综述旨在吸引研究人员关注这一前景广阔的领域。整合有关 AFPs 的知识可为开发具有广谱活性、降低毒性、靶向作用和限制病原真菌抗药性机制的新型抗真菌药物铺平道路,从而为抗真菌疗法带来重大进展。
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引用次数: 0
Exploring the antibiotic resistance of Listeria monocytogenes in food environments - a review. 探索食品环境中李斯特菌的抗生素耐药性--综述。
IF 6 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-15 DOI: 10.1080/1040841X.2024.2412007
Cristina Díaz-Martínez, Araceli Bolívar, Birce Mercanoglu Taban, Nazlı Kanca, Fernando Pérez-Rodríguez

Listeria monocytogenes, a resilient bacterium in diverse food conditions, such as refrigeration, reduced water activity and low pH, poses a significant threat to the food industry and public health. In recent years, it has been documented an increase in the antibiotic resistance of zoonotic pathogens, including L. monocytogenes. This review provides new insight into the molecular mechanisms involved in both intrinsic and acquired antibiotic resistance of L. monocytogenes with an emphasis on the effect of different environmental and food-related factors. It also explores the relationship of these resistance mechanisms with virulence factors. An analysis of literature data (2009-2021) was conducted to investigate statistically and graphically potential associations between specific antibiotic resistance patterns in the pathogen and food categories using an unbiased variance analysis. The results evidenced that food type had an influence on the antibiotic resistance profiles of L. monocytogenes, with meat and vegetables being the food categories exhibiting the most prevalent profiles. The frequent detection of resistance to ampicillin, penicillin, and tetracycline (non-intrinsic resistances) indicates that specific processing conditions along the food chain may induce them. Many questions remain about the impact of food chain factors (e.g. thermal treatments, cold chain, preservatives, etc.) and food type (low pH, reduced water activity, etc.) on the antibiotic resistance patterns of the pathogen, particularly concerning food-related sources, the resistance mechanisms involved (e.g. cross-protection, horizontal gene transfer, etc.), and the evolutionary processes of antibiotic-resistant microbial populations. Metagenomics, in addition to other -omics technologies (metabolomics and transcriptomics), allows a better understanding of the processes involved in the acquisition of resistance.

单核细胞增生李斯特菌是一种在冷藏、水活性降低和低 pH 值等各种食品条件下都能存活的细菌,对食品工业和公众健康构成重大威胁。近年来,包括单核细胞增多性乳酸杆菌在内的人畜共患病原体的抗生素耐药性有所增加。这篇综述对单核细胞增生葡京手机投注平台内在和获得性抗生素耐药性所涉及的分子机制提供了新的见解,重点是不同环境和食品相关因素的影响。它还探讨了这些耐药性机制与毒力因素之间的关系。对文献数据(2009-2021 年)进行了分析,采用无偏差方差分析法,以统计和图表形式研究病原体和食物类别中特定抗生素耐药性模式之间的潜在关联。结果表明,食物类型对单核细胞增多性酵母菌的抗生素耐药性特征有影响,肉类和蔬菜是表现出最普遍特征的食物类别。氨苄西林、青霉素和四环素(非内在耐药性)耐药性的频繁检测表明,食物链上的特定加工条件可能会诱发这些耐药性。关于食物链因素(如热处理、冷链、防腐剂等)和食物类型(低 pH 值、水活性降低等)对病原体抗生素耐药性模式的影响,尤其是与食物有关的来源、涉及的耐药性机制(如交叉保护、水平基因转移等)以及耐抗生素微生物种群的进化过程,仍存在许多问题。除其他组学技术(代谢组学和转录组学)外,元基因组学还能更好地了解抗药性的获得过程。
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引用次数: 0
The battle within: how Pseudomonas aeruginosa uses host-pathogen interactions to infect the human lung. 内部斗争:铜绿假单胞菌如何利用宿主与病原体之间的相互作用感染人类肺部。
IF 6 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1080/1040841X.2024.2407378
Carmen Mesas Vaz, Alba Guembe Mülberger, Marc Torrent Burgas

Pseudomonas aeruginosa is a versatile Gram-negative pathogen known for its ability to invade the respiratory tract, particularly in cystic fibrosis patients. This review provides a comprehensive analysis of the multifaceted strategies for colonization, virulence, and immune evasion used by P. aeruginosa to infect the host. We explore the extensive protein arsenal of P. aeruginosa, including adhesins, exotoxins, secreted proteases, and type III and VI secretion effectors, detailing their roles in the infective process. We also address the unique challenge of treating diverse lung conditions that provide a natural niche for P. aeruginosa on the airway surface, with a particular focus in cystic fibrosis. The review also discusses the current limitations in treatment options due to antibiotic resistance and highlights promising future approaches that target host-pathogen protein-protein interactions. These approaches include the development of new antimicrobials, anti-attachment therapies, and quorum-sensing inhibition molecules. In summary, this review aims to provide a holistic understanding of the pathogenesis of P. aeruginosa in the respiratory system, offering insights into the underlying molecular mechanisms and potential therapeutic interventions.

铜绿假单胞菌是一种多发性革兰氏阴性病原体,以其侵入呼吸道的能力而闻名,尤其是在囊性纤维化患者中。本综述全面分析了铜绿假单胞菌用于感染宿主的定植、毒力和免疫逃避等多方面策略。我们探讨了铜绿假单胞菌广泛的蛋白质库,包括粘附素、外毒素、分泌蛋白酶以及 III 型和 VI 型分泌效应物,详细介绍了它们在感染过程中的作用。我们还探讨了治疗各种肺部疾病所面临的独特挑战,这些疾病为气道表面的铜绿假单胞菌提供了天然的生存环境,其中特别关注囊性纤维化。综述还讨论了目前由于抗生素耐药性而导致的治疗方案的局限性,并重点介绍了针对宿主-病原体蛋白-蛋白相互作用的前景广阔的未来方法。这些方法包括开发新的抗菌剂、抗附着疗法和法定人数感应抑制分子。总之,本综述旨在提供对呼吸系统中铜绿假单胞菌致病机理的整体认识,提供对潜在分子机制和潜在治疗干预措施的见解。
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引用次数: 0
Antimicrobial and antibiofilm properties of procyanidins: potential for clinical and biotechnological applications. 原花青素的抗菌和抗生物膜特性:临床和生物技术应用潜力。
IF 6 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-20 DOI: 10.1080/1040841X.2024.2404509
Mariana M G Mattos, Sérgio Antunes Filho, Gabriel R Martins, Lara Souza Venturi, Vinícius Benjamim Canetti, Fabienne Antunes Ferreira, Debora Foguel, Ayla Sant'Ana da Silva

Procyanidins (PCs) have emerged as agents with potential antimicrobial and antibiofilm activities, although their mechanisms of action and structure-activity relationships remain poorly understood. This review assessed the potential mechanisms of action and applications of these compounds to explore these aspects. Studies on the antimicrobial properties of PCs suggest that they are involved in osmotic imbalance, DNA interactions and metabolic disruption. Although less studied, their antibiofilm activities include antiadhesive effects and the modulation of mobility and quorum sensing. However, most research has used uncharacterized plant extracts for in vitro assays, limiting the understanding of the structure-activity relationships of PCs and their in vivo mechanisms. Clinical trials on the antimicrobial and antibiofilm properties of PCs have not clarified these issues due to nonstandardized methodologies, inadequate chemical characterization, and the limited number of studies, preventing a consensus and evaluation of the in vivo effects. Additionally, patent analysis revealed that technological developments in the antimicrobial and antibiofilm uses of PCs are concentrated in health care and dental care, but new biotechnological uses are emerging. Therefore, while PCs are promising antimicrobial and antibiofilm compounds, further research into their chemical structures and mechanisms of action is crucial for evidence-based applications in biotechnology and health care.

原花青素(PCs)已成为具有潜在抗菌和抗生物膜活性的制剂,但人们对其作用机制和结构-活性关系仍然知之甚少。本综述对这些化合物的潜在作用机制和应用进行了评估,以探讨这些方面的问题。对多氯化萘抗菌特性的研究表明,多氯化萘参与了渗透失衡、DNA 相互作用和新陈代谢破坏。虽然研究较少,但它们的抗生物膜活性包括抗粘附作用、调节流动性和法定人数感应。然而,大多数研究都使用未定性的植物提取物进行体外检测,从而限制了对多氯化萘结构-活性关系及其体内机制的了解。由于方法不规范、化学特征描述不充分以及研究数量有限,有关多氯联苯抗菌和抗生物膜特性的临床试验尚未澄清这些问题,因此无法就体内效应达成共识和进行评估。此外,专利分析表明,多氯联苯抗菌和抗生物膜方面的技术发展主要集中在医疗保健和牙科护理领域,但新的生物技术用途正在出现。因此,虽然多氯联苯是很有前景的抗菌和抗生物膜化合物,但进一步研究其化学结构和作用机制对于生物技术和医疗保健领域的循证应用至关重要。
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引用次数: 0
Precise pathogen quantification by CRISPR-Cas: a sweet but tough nut to crack. 利用 CRISPR-Cas 对病原体进行精确定量:甜蜜但难以攻克的难题。
IF 6.5 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-17 DOI: 10.1080/1040841x.2024.2404041
Zhihao Yao,Wanglu Li,Kaiyu He,Hongmei Wang,Yan Xu,Xiahong Xu,Qun Wu,Liu Wang
Pathogen detection is increasingly applied in medical diagnosis, food processing and safety, and environmental monitoring. Rapid, sensitive, and accurate pathogen quantification is the most critical prerequisite for assessing protocols and preventing risks. Among various methods evolved, those based on clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins (Cas) have been developed as important pathogen detection strategies due to their distinct advantages of rapid target recognition, programmability, ultra-specificity, and potential for scalability of point-of-care testing (POCT). However, arguments and concerns on the quantitative capability of CRISPR-based strategies are ongoing. Herein, we systematically overview CRISPR-based pathogen quantification strategies according to the principles, properties, and application scenarios. Notably, we review future challenges and perspectives to address the of precise pathogen quantification by CRISPR-Cas. We hope the insights presented in this review will benefit development of CRISPR-based pathogen detection methods.
病原体检测越来越多地应用于医疗诊断、食品加工和安全以及环境监测。快速、灵敏和准确的病原体定量是评估方案和预防风险的最关键前提。在已发展出的各种方法中,基于聚类规律性间隔短回文重复序列(CRISPR)相关蛋白(Cas)的方法因其快速目标识别、可编程性、超特异性和潜在的床旁检测(POCT)可扩展性等独特优势,已被开发为重要的病原体检测策略。然而,关于基于CRISPR策略的定量能力的争论和担忧仍在继续。在此,我们根据原理、特性和应用场景系统地概述了基于 CRISPR 的病原体定量策略。值得注意的是,我们回顾了通过 CRISPR-Cas 实现病原体精确定量的未来挑战和前景。我们希望这篇综述中提出的见解将有助于开发基于 CRISPR 的病原体检测方法。
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引用次数: 0
Male-specific bacteriophages and their potential on combating the spreading of T4SS-bearing antimicrobial resistance plasmids. 雄性特异性噬菌体及其在阻止携带 T4SS 的抗菌性质粒传播方面的潜力。
IF 6.5 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-10 DOI: 10.1080/1040841x.2024.2400150
Jun Li,Pilar García,Xing Ji,Ran Wang,Tao He
Antimicrobial resistance (AMR) has been recognized as an important health crisis in the twenty first century. Type IV secretion systems (T4SSs) play key roles in the dissemination of AMR plasmids. Novel strategies that combat AMR problem by targeting T4SS sprung up in recent years. Here, we focus on the strategy of male-specific phages that could target and kill bacteria carrying conjugative AMR plasmids encoding T4SSs. We reviewed the recent advances in male-specific phages, including anti-conjugation mechanisms, clinical isolation and identification methods, classification and characteristics, in vitro and in vivo anti-conjugation efficacy and improving strategies. Male-specific phages constitute exciting candidates for developing sustainable anti-resistance biocontrol applications.
抗菌素耐药性(AMR)已被认为是二十一世纪的一个重要健康危机。IV 型分泌系统(T4SS)在 AMR 质粒的传播过程中发挥着关键作用。近年来,通过靶向 T4SS 解决 AMR 问题的新策略层出不穷。在这里,我们重点讨论了雄性特异性噬菌体的策略,这种噬菌体可以靶向杀死携带编码 T4SS 的共轭型 AMR 质粒的细菌。我们回顾了雄性特异性噬菌体的最新进展,包括抗共轭机制、临床分离和鉴定方法、分类和特征、体外和体内抗共轭功效以及改进策略。雄性特异性噬菌体是开发可持续抗药性生物控制应用的令人兴奋的候选物质。
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引用次数: 0
Pseudomonas aeruginosa: metabolic allies and adversaries in the world of polymicrobial infections. 铜绿假单胞菌:多微生物感染世界中的代谢盟友和对手。
IF 6 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-03 DOI: 10.1080/1040841X.2024.2397359
Chandni Sachdeva, Kapaettu Satyamoorthy, Thokur Sreepathy Murali

Pseudomonas aeruginosa (PA), an opportunistic human pathogen that is frequently linked with chronic infections in immunocompromised individuals, is also metabolically versatile, and thrives in diverse environments. Additionally, studies report that PA can interact with other microorganisms, such as bacteria, and fungi, producing unique metabolites that can modulate the host immune response, and contribute to disease pathogenesis. This review summarizes the current knowledge related to the metabolic interactions of PA with other microorganisms (Staphylococcus, Acinetobacter, Klebsiella, Enterococcus, and Candida) and human hosts, and the importance of these interactions in a polymicrobial context. Further, we highlight the potential applications of studying these metabolic interactions toward designing better diagnostic tools, and therapeutic strategies to prevent, and treat infections caused by this pathogen.

铜绿假单胞菌(Pseudomonas aeruginosa,PA)是一种机会性人类病原体,经常与免疫力低下人群的慢性感染有关。此外,有研究报告称,PA 能与细菌和真菌等其他微生物相互作用,产生独特的代谢产物,从而调节宿主的免疫反应,促进疾病的发病。本综述总结了 PA 与其他微生物(葡萄球菌、醋烷杆菌、克雷伯氏菌、肠球菌和念珠菌)和人类宿主的代谢相互作用的现有相关知识,以及这些相互作用在多微生物背景下的重要性。此外,我们还强调了研究这些代谢相互作用对设计更好的诊断工具和治疗策略的潜在应用,以预防和治疗由这种病原体引起的感染。
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引用次数: 0
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Critical Reviews in Microbiology
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