关键词: Acinetobacter baumannii genomic analysis heterogeneous novel antibiotic development panel phenotypes

Mesh : Acinetobacter baumannii / drug effects genetics growth & development Anti-Bacterial Agents / pharmacology Humans Acinetobacter Infections / microbiology drug therapy Phenotype Biofilms / drug effects growth & development Genotype Microbial Sensitivity Tests Virulence / genetics Drug Development Drug Resistance, Multiple, Bacterial / genetics Drug Resistance, Bacterial / genetics

来  源:   DOI:10.1128/spectrum.00086-24   PDF(Pubmed)

Abstract:
Acinetobacter baumannii is one of the most important pathogens worldwide. The intrinsic and acquired resistance of A. baumannii, coupled with the slow pace of novel antimicrobial drug development, poses an unprecedented and enormous challenge to clinical anti-infective therapy of A. baumannii. Recent studies in the field of pathogenicity, antibiotic resistance, and biofilms of A. baumannii have focused on the model strains, including ATCC 17978, ATCC 19606, and AB5075. However, these model strains represent only a limited portion of the heterogeneity in A. baumannii. Furthermore, variants of these model strains have emerged that show significant diversity not only at the genotypic level but also reflected in differences at the phenotypic levels of capsule, virulence, pathogenicity, and antibiotic resistance. Research on A. baumannii, a key pathogen, would benefit from a standardized approach, which characterizes heterogeneous strains in order to facilitate rapid diagnosis, discovery of new therapeutic targets, and efficacy assessment. Our study provides and describes a standardized, genomically and phenotypically heterogeneous panel of 45 different A. baumannii strains for the research community. In addition, we performed comparative analyses of several phenotypes of this panel. We found that the sequence type 2 (ST2) group showed significantly higher rates of resistance, lower fitness cost for adaptation, and yet less biofilm formation. The Macrocolony type E (MTE, flat center and wavy edge phenotype reported in the literature) group showed a less clear correlation of resistance rates and growth rate, but was observed to produce more biofilms. Our study sheds light on the complex interplay of resistance fitness and biofilm formation within distinct strains, offering insights crucial for combating A. baumannii infection.
OBJECTIVE: Acinetobacter baumannii is globally notorious, and in an effort to combat the spread of such pathogens, several emerging candidate therapies have already surfaced. However, the strains used to test these therapies vary across studies (the sources and numbers of test strains are varied and often very large, with little heterogeneity). The variation complicates the studies. Furthermore, the limited standardized resources of A. baumannii strains have greatly restricted the research on the physiology, pathogenicity, and antibiotic resistance. Therefore, it is crucial for the research community to acquire a standardized and heterogeneous panel of A. baumannii. Our study meticulously selected 45 diverse A. baumannii strains from a total of 2,197 clinical isolates collected from 64 different hospitals across 27 provinces in China, providing a scientific reference for the research community. This assistance will significantly facilitate scientific exchange in academic research.
摘要:
鲍曼不动杆菌是世界范围内最重要的病原体之一。鲍曼不动杆菌的内在和后天抗性,再加上新型抗菌药物开发的缓慢步伐,对鲍曼不动杆菌的临床抗感染治疗提出了前所未有的巨大挑战。致病性领域的最新研究,抗生素耐药性,鲍曼不动杆菌的生物膜集中在模型菌株上,包括ATCC17978、ATCC19606和AB5075。然而,这些模型菌株仅代表鲍曼不动杆菌异质性的有限部分。此外,这些模型菌株的变体已经出现,不仅在基因型水平上显示出显著的多样性,而且在胶囊的表型水平上也反映出差异,毒力,致病性,抗生素耐药性。鲍曼不动杆菌的研究,一个关键的病原体,将受益于标准化方法,它表征了异质菌株,以便于快速诊断,发现新的治疗靶点,和疗效评估。我们的研究提供并描述了一个标准化的,45种不同鲍曼不动杆菌菌株的基因组和表型异质性小组。此外,我们对该组的几种表型进行了比较分析.我们发现,序列2型(ST2)组表现出明显更高的耐药率,较低的适应健身成本,和更少的生物膜形成。E型大菌落(MTE,文献中报道的平坦中心和波浪形边缘表型)组显示出抗性率和生长速率之间不太明显的相关性,但被观察到产生更多的生物膜。我们的研究揭示了不同菌株中阻力适应性和生物膜形成的复杂相互作用,提供对对抗鲍曼不动杆菌感染至关重要的见解。
目的:鲍曼不动杆菌在全球范围内臭名昭著,为了对抗这种病原体的传播,几种新兴的候选疗法已经浮出水面。然而,用于测试这些疗法的菌株在研究中有所不同(测试菌株的来源和数量各不相同,并且通常非常大,几乎没有异质性)。这种变化使研究复杂化。此外,鲍曼不动杆菌的标准化资源有限,极大地限制了其生理学研究,致病性,抗生素耐药性。因此,对于研究界来说,获得鲍曼不动杆菌的标准化和异质性小组至关重要。我们的研究从来自中国27个省的64个不同医院的总共2,197个临床分离株中精心选择了45个不同的鲍曼不动杆菌菌株。为研究界提供科学参考。这种援助将大大促进学术研究中的科学交流。
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