Di Gregorio Sabrina, Haim María Sol, Famiglietti Ángela María Rosa, Di Conza José, Mollerach Marta
Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1113, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires 1113, Argentina.
Antibiotics (Basel). 2023 Feb 11;12(2):372. doi: 10.3390/antibiotics12020372.
Infections due to vancomycin-intermediate (VISA) and heterogeneous VISA (hVISA) represent a serious concern due to their association with vancomycin treatment failure. However, the underlying molecular mechanism responsible for the hVISA/VISA phenotype is complex and not yet fully understood. We have previously characterized two ST100-MRSA-hVISA clinical isolates recovered before and after 40 days of vancomycin treatment (D1 and D2, respectively) and two in vitro VISA derivatives (D23C9 and D2P11), selected independently from D2 in the presence of vancomycin. This follow-up study was aimed at further characterizing these isogenic strains and obtaining their whole genome sequences to unravel changes associated with antibiotic resistance. It is interesting to note that none of these isogenic strains carry SNPs in the regulatory operons , and/or . Nonetheless, genetic changes including SNPs, INDELs and IS genomic insertions/rearrangements were found both in in vivo and in vitro vancomycin-selected strains. Some were found in the downstream target genes of the aforementioned regulatory operons, which are involved in cell wall and phosphate metabolism, staphylococcal growth and biofilm formation. Some of the genetic changes reported herein have not been previously associated with vancomycin, daptomycin and/or oxacillin resistance in .
万古霉素中介（VISA）和异质性VISA（hVISA）引起的感染因其与万古霉素治疗失败相关而备受关注。然而，导致hVISA/VISA表型的潜在分子机制复杂，尚未完全明确。我们之前已对两株ST100-MRSA-hVISA临床分离株进行了特征分析，这两株菌分别在万古霉素治疗40天之前和之后获得（分别为D1和D2），还对两株体外VISA衍生物（D23C9和D2P11）进行了特征分析，这两株衍生物是在万古霉素存在的情况下从D2独立筛选出来的。这项后续研究旨在进一步对这些同基因菌株进行特征分析，并获取它们的全基因组序列，以揭示与抗生素耐药性相关的变化。值得注意的是，这些同基因菌株在调控操纵子 、 和 中均未携带单核苷酸多态性（SNP）。尽管如此，在体内和体外经万古霉素筛选的菌株中均发现了包括SNP、插入缺失（INDEL）和插入序列（IS）基因组插入/重排在内的基因变化。其中一些变化出现在上述调控操纵子的下游靶基因中，这些靶基因参与细胞壁和磷酸盐代谢、葡萄球菌生长及生物膜形成。本文报道的一些基因变化此前尚未与金黄色葡萄球菌对万古霉素、达托霉素和/或苯唑西林的耐药性相关联。
