Vázquez Xenia, García Patricia, Fernández Javier, Ladero Víctor, Rodríguez-Lucas Carlos, Heinisch Jürgen J, Rodicio Rosaura, Rodicio M Rosario
Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo (UO), 33006 Oviedo, Spain.
Grupo de Microbiología Traslacional, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.
Antibiotics (Basel). 2025 Jul 16;14(7):711. doi: 10.3390/antibiotics14070711.
BACKGROUND/OBJECTIVE: The present study focused on the analysis of the Spanish clone belonging to the successful 4,[5],12:i:- monophasic variant of serovar Typhimurium.
All isolates of the clone recovered in a Spanish region from human clinical samples between 2008 and 2018 (N = 14) were investigated using microbiological approaches and genome sequence analysis. In addition, they were compared with isolates from the years 2000 to 2003 (N = 21), which were previously characterized but had not yet been sequenced.
Phylogenetic analyses indicate that all isolates are closely related (differing by 1 to 103 SNPs) but belong to two clades termed A and B. With few exceptions, clade A comprised isolates of the first period, also including two "older" control strains, LSP 389/97 and LSP 272/98. Clade B only contained isolates from the second period. Isolates from both periods were resistant to antibiotics and biocides, with almost all resistance genes located on large IncC plasmids, additionally carrying pSLT-derived virulence genes. The number of resistance genes was highly variable, resulting in a total of 22 ABR (antibiotic biocide resistance) profiles. The number of antibiotic resistance genes, but not that of biocide resistance genes, was considerably lower in isolates from the second than from the first period (with averages of 5.5 versus 9.6 genes). Importantly, IS, which resides in multiple copies within these plasmids, appears to be playing a crucial role in the evolution of resistance, and it was also responsible for the monophasic phenotype, which was associated with four different deletions eliminating the region.
the observed reduction in the number of antibiotic resistance genes could correlate with the loss of adaptive advantage originating from the ban on the use of antibiotics as feed additives implemented in the European Union since 2006, facilitated by the intrinsic instability of the IncC plasmids. Two consecutive IS transposition events, which can explain both the clonal relationship of the isolates and their variability, may account for the observed deletions.
背景/目的：本研究聚焦于对属于鼠伤寒沙门氏菌成功的4,[5],12:i:-单相变体的西班牙克隆进行分析。
使用微生物学方法和基因组序列分析，对2008年至2018年间在西班牙一个地区从人类临床样本中分离出的该克隆的所有菌株（N = 14）进行了研究。此外，将它们与2000年至2003年分离出的菌株（N = 21）进行了比较，这些菌株先前已进行过特征描述但尚未测序。
系统发育分析表明，所有菌株密切相关（单核苷酸多态性差异为1至103个），但属于两个分支，称为A和B。除少数例外，A分支包含第一时期的菌株，还包括两个“较老”的对照菌株，LSP 389/97和LSP 272/98。B分支仅包含第二时期的菌株。两个时期的菌株均对抗生素和杀生物剂耐药，几乎所有耐药基因都位于大型IncC质粒上，此外还携带源自pSLT的毒力基因。耐药基因的数量高度可变，总共产生了22种抗生素杀生物剂耐药（ABR）谱。第二时期菌株中的抗生素耐药基因数量明显低于第一时期（平均分别为5.5个和9.6个基因），但杀生物剂耐药基因数量并非如此。重要的是，存在于这些质粒中的多个拷贝的插入序列（IS）似乎在耐药性进化中起关键作用，并且它还导致了单相表型，这与消除该区域的四种不同缺失有关。
观察到的抗生素耐药基因数量减少可能与自2006年欧盟实施禁止将抗生素用作饲料添加剂以来，由于IncC质粒的固有不稳定性而导致的适应性优势丧失有关。两次连续的IS转座事件可以解释菌株的克隆关系及其变异性，可能是观察到的缺失的原因。
