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十年的耐碳青霉烯类药物的基因组和表型适应性

A decade of genomic and phenotypic adaptation of carbapenem-resistant .

作者信息

Tagueha Astri D, D'Agostini Cartesio, Scribano Daniela, Fiorilla Carlotta, Limongi Dolores, Fillo Silvia, Corrent Luca, Lipari Martina, Lista Florigio, Nencioni Lucia, Palamara Anna Teresa, Ambrosi Cecilia

机构信息

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.

出版信息

Front Cell Infect Microbiol. 2025 Apr 30;15:1527488. doi: 10.3389/fcimb.2025.1527488. eCollection 2025.

DOI:10.3389/fcimb.2025.1527488
PMID:40370403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12075148/
Abstract

INTRODUCTION

exhibits high genomic plasticity, enabling it to acquire virulence factors and antibiotic resistance (AR). Understanding its evolutionary adaptations is crucial for developing effective therapeutic strategies.

METHODS

Thirty clinical isolates collected from two distinct time periods, defined as older (2010-2013), and recent (2022-2023),- were compared phenotypically (antibiotic resistance, growth, biofilm formation, desiccation tolerance, invasiveness) and genotypically (whole-genome sequencing).

RESULTS

All isolates displayed an extensively drug-resistant phenotype. Overall, respiratory isolates harbored a higher content of antibiotic-resistant genes (ARGs), with older isolates showing 12.5% increases in the average number of ARGs compared to recent urine isolates ( = 0.02). More than 50% of the strains with faster growth, stronger biofilm formation, and increased lung cell invasiveness were recent respiratory isolates, while over 70% of older isolates showed greater desiccation tolerance and bladder cell invasiveness. Eleven virulence factor genes were shared between old and recent respiratory isolates, and eight were common between recent urinary and respiratory strains with no overlap among urinary isolates. Statistically significant positive correlations were observed between fast-growing and strong biofilm-forming respiratory isolates as well as their lung cell invasiveness. Conversely, negative correlations were found between collection time, isolation site, and host cell invasiveness. Analysis of macrocolony types revealed no link to phenotypic behavior.

CONCLUSION

Significant genetic variability was found between past and recent isolates. Older isolates had more genes involved in adhesion and nutrient uptake, while recent respiratory strains demonstrated increased biofilm formation and invasiveness, reflecting adaptation to clinical pressures. These findings highlight the dynamic evolution of , providing insights for future therapeutic strategies and infection control.

摘要

引言

表现出高度的基因组可塑性,使其能够获得毒力因子和抗生素耐药性(AR)。了解其进化适应性对于制定有效的治疗策略至关重要。

方法

比较了从两个不同时间段收集的30株临床分离株,分别定义为较早时期(2010 - 2013年)和近期(2022 - 2023年),在表型(抗生素耐药性、生长、生物膜形成、耐干燥性、侵袭性)和基因型(全基因组测序)方面的差异。

结果

所有分离株均表现出广泛耐药表型。总体而言,呼吸道分离株携带的抗生素耐药基因(ARGs)含量更高,较早分离株的ARGs平均数量比近期尿液分离株增加了12.5%(P = 0.02)。生长较快、生物膜形成较强且肺细胞侵袭性增加的菌株中,超过50%是近期呼吸道分离株,而超过70%的较早分离株表现出更强的耐干燥性和膀胱细胞侵袭性。在较早和近期呼吸道分离株之间共有11个毒力因子基因,近期尿液和呼吸道菌株之间有8个基因相同,尿液分离株之间无重叠。在生长快速和生物膜形成较强的呼吸道分离株及其肺细胞侵袭性之间观察到统计学上显著的正相关。相反,在采集时间、分离部位和宿主细胞侵袭性之间发现了负相关。对大菌落类型的分析未发现与表型行为的关联。

结论

在过去和近期的分离株之间发现了显著的遗传变异性。较早的分离株有更多参与黏附和营养摄取的基因,而近期呼吸道菌株表现出生物膜形成和侵袭性增加,反映了对临床压力的适应。这些发现突出了 的动态进化,为未来的治疗策略和感染控制提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/cdb4b7ebc1c4/fcimb-15-1527488-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/986dc1350de1/fcimb-15-1527488-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/670dff5b469d/fcimb-15-1527488-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/469fbc0bdc77/fcimb-15-1527488-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/3d832b2fdba9/fcimb-15-1527488-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/9ac8cca83699/fcimb-15-1527488-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/cdb4b7ebc1c4/fcimb-15-1527488-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/986dc1350de1/fcimb-15-1527488-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/3c61d5c06b6a/fcimb-15-1527488-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/670dff5b469d/fcimb-15-1527488-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/4ddc7f809001/fcimb-15-1527488-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/469fbc0bdc77/fcimb-15-1527488-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/3d832b2fdba9/fcimb-15-1527488-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/9ac8cca83699/fcimb-15-1527488-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc9/12075148/cdb4b7ebc1c4/fcimb-15-1527488-g008.jpg

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