Bianconi Irene, Esposito Alfonso, Piazza Silvano, Piffer Elena, Pagani Elisabetta, Jousson Olivier
Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Trento, Italy.
Laboratory of Microbiology and Virology, Provincial Hospital of Bolzano (SABES-ASDAA), Lehrkrankenhaus der Paracelsus Medizinischen Privatuniversität, Bolzano, Italy.
Front Microbiol. 2025 Aug 6;16:1569118. doi: 10.3389/fmicb.2025.1569118. eCollection 2025.
represents a paradigm for studies on antibiotic resistance. Nevertheless, despite the considerable number of genome sequences that have been released in recent years, there is still a paucity of knowledge regarding the genomic determinants of the typical phenotypic traits associated with pulmonary infection.
The genomes of 40 strains of were sequenced over an 8-year period (2007-2014), isolated from the sputum of a single patient with cystic fibrosis in Trentino, Italy. The same isolates were characterised for a panel of 14 phenotypes, including biofilm formation, antibiotic resistance, secretion of siderophores and virulence factors. The phylogenetic coherence of the measured phenotypes was determined in relation to the tree based on single-nucleotide polymorphisms (SNPs). Subsequently, the semantic framework for comparative functional genomics (SAPP) was employed to investigate the depletion or enrichment of specific protein functional domains within the population in relation to the observed phenotypes.
The majority of our findings regarding phenotypic adaptation over time were consistent with the population structure and followed the evolutionary pathways described in the literature. However, an exact relationship between the presence of genes and specific phenotypes could not be established. The SAPP approach enabled the identification of 189 protein domains that were significantly enriched in antibiotic-resistant strains, as well as 87 domains associated with other phenotypic adaptations. In some cases, the domains were commonly associated with antibiotic resistances, for example, outer membrane efflux pumps and porins. However, we also detected a number of domains with unknown function.
Our findings provide a foundation for a more comprehensive understanding of the phenotypic adaptations occurring during microevolution in lung environments and facilitate the identification of new targets for the design of novel antimicrobial agents.
代表了抗生素耐药性研究的一个范例。然而，尽管近年来已公布了大量的基因组序列，但对于与肺部感染相关的典型表型特征的基因组决定因素，仍然缺乏了解。
在8年期间（2007 - 2014年）对来自意大利特伦蒂诺一名患有囊性纤维化患者痰液中分离出的40株菌株的基因组进行了测序。对同一批分离株进行了14种表型的鉴定，包括生物膜形成、抗生素耐药性、铁载体分泌和毒力因子。根据单核苷酸多态性（SNP）确定所测表型与树状图相关的系统发育一致性。随后，采用比较功能基因组学的语义框架（SAPP）来研究群体中特定蛋白质功能域相对于观察到的表型的缺失或富集情况。
我们关于表型随时间适应的大多数发现与群体结构一致，并遵循文献中描述的进化途径。然而，无法确定基因的存在与特定表型之间的确切关系。SAPP方法能够鉴定出在抗生素耐药菌株中显著富集的189个蛋白质结构域，以及与其他表型适应相关的87个结构域。在某些情况下，这些结构域通常与抗生素耐药性相关，例如外膜流出泵和孔蛋白。然而，我们也检测到一些功能未知的结构域。
我们的发现为更全面地理解肺部环境中微进化过程中发生的表型适应提供了基础，并有助于确定新型抗菌剂设计的新靶点。
