Gagetti Paula, Rosato Roberto R, Rosato Adriana E
Servicio Antimicrobianos, INEI-ANLIS, Buenos Aires 1281, Argentina.
Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA.
Antibiotics (Basel). 2021 Oct 26;10(11):1299. doi: 10.3390/antibiotics10111299.
is an important pathogen responsible for infections in dogs and in humans. The emergence and dissemination of methicillin-resistant (MRSP) and the multidrug resistance frequently seen in this species make difficult the treatment of these pathogens. The cefoxitin disk is widely used as a marker of methicillin resistance mediated by the gene in and other staphylococcal species; however, it is not useful to detect β-lactam resistance of MRSP in clinical microbiology laboratories. The purpose of this study was to elucidate the molecular bases of the dissociated phenotype between oxacillin and cefoxitin antibiotics. By using a combinatorial approach that included the Penicillin-Binding Proteins' (PBP) profile, their affinity for different β-lactam antibiotics and the analyses of PBPs' sequence, we provide evidence that PBP4 showed still affinity for its target cefoxitin, impairing its phenotypic resistant detection in MRSP. Together, these findings provide evidence that PBP4 is directly associated with the dissociated oxacillin and cefoxitin phenotype.
是导致犬类和人类感染的重要病原体。耐甲氧西林（MRSP）的出现和传播以及该菌种中常见的多药耐药性使得这些病原体的治疗变得困难。头孢西丁纸片被广泛用作检测由基因介导的甲氧西林耐药性的标志物，用于检测葡萄球菌属及其他葡萄球菌菌种；然而，在临床微生物实验室中，它对于检测MRSP的β-内酰胺耐药性并无用处。本研究的目的是阐明奥沙西林和头孢西丁抗生素之间解离表型的分子基础。通过使用包括青霉素结合蛋白（PBP）谱、它们对不同β-内酰胺抗生素的亲和力以及PBP序列分析在内的组合方法，我们提供了证据表明PBP4对其靶标头孢西丁仍具有亲和力，从而损害了其在MRSP中的表型耐药性检测。总之，这些发现提供了证据表明PBP4与奥沙西林和头孢西丁的解离表型直接相关。
