Nascimento Ana P B, Ortiz Mauro F, Martins Willames M B S, Morais Guilherme L, Fehlberg Lorena C C, Almeida Luiz G P, Ciapina Luciane P, Gales Ana C, Vasconcelos Ana T R
Laboratório de Bioinformática, Laboratório Nacional de Computação Científica Petrópolis, Brazil.
Laboratório Alerta, Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
Front Microbiol. 2016 Dec 5;7:1946. doi: 10.3389/fmicb.2016.01946. eCollection 2016.
Carbapenems represent the mainstay therapy for the treatment of serious infections. However, the emergence of carbapenem resistance has jeopardized the clinical use of this important class of compounds. The production of SPM-1 metallo-β-lactamase has been the most common mechanism of carbapenem resistance identified in isolated from Brazilian medical centers. Interestingly, a single SPM-1-producing clone belonging to the ST277 has been widely spread within the Brazilian territory. In the current study, we performed a next-generation sequencing of six SPM-1-producing ST277 isolates. The core genome contains 5899 coding genes relative to the reference strain a PAO1. A total of 26 genomic islands were detected in these isolates. We identified remarkable elements inside these genomic islands, such as copies of the gene conferring resistance to carbapenems and a type I-C CRISPR-Cas system, which is involved in protection of the chromosome against foreign DNA. In addition, we identified single nucleotide polymorphisms causing amino acid changes in antimicrobial resistance and virulence-related genes. Together, these factors could contribute to the marked resistance and persistence of the SPM-1-producing ST277 clone. A comparison of the SPM-1-producing ST277 genomes showed that their core genome has a high level nucleotide similarity and synteny conservation. The variability observed was mainly due to acquisition of genomic islands carrying several antibiotic resistance genes.
碳青霉烯类药物是治疗严重感染的主要疗法。然而,碳青霉烯耐药性的出现危及了这类重要化合物的临床应用。产SPM-1金属β-内酰胺酶一直是巴西医疗中心分离出的菌株中最常见的碳青霉烯耐药机制。有趣的是,属于ST277的单一产SPM-1克隆已在巴西境内广泛传播。在本研究中,我们对6株产SPM-1的ST277分离株进行了二代测序。相对于参考菌株PAO1,核心基因组包含5899个编码基因。在这些分离株中总共检测到26个基因组岛。我们在这些基因组岛内鉴定出显著元件,如赋予碳青霉烯耐药性的基因拷贝和一个I-C型CRISPR-Cas系统,该系统参与保护染色体免受外源DNA的侵害。此外,我们鉴定出导致抗菌耐药性和毒力相关基因中氨基酸变化的单核苷酸多态性。这些因素共同促成了产SPM-1的ST277克隆的显著耐药性和持久性。对产SPM-1的ST277基因组的比较表明,它们的核心基因组具有高度的核苷酸相似性和共线性保守性。观察到的变异性主要归因于携带多个抗生素耐药基因的基因组岛的获得。