Expression of high-level methicillin resistance in Staphylococcus aureus from the Staphylococcus sciuri mecA homologue:: Role of mutation(s) in the genetic background and in the coding region of mecA
Expression of high-level methicillin resistance in Staphylococcus aureus from the Staphylococcus sciuri mecA homologue:: Role of mutation(s) in the genetic background and in the coding region of mecA
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DOI：
10.1089/mdr.2005.11.215
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发表时间：
2005-09-01
影响因子：
2.6
通讯作者：
Tomasz, A
中科院分区：
文献类型：
--
作者：
Wu, SW;De Lencastre, H;Tomasz, A
耐甲氧西林金黄色葡萄球菌（MRSA）中的主要耐药决定簇mecA基因的密切同源物在动物寄生物种松鼠葡萄球菌中普遍存在，但该葡萄球菌物种的大多数分离株对β-内酰胺类抗生素（包括甲氧西林）敏感。最近，我们发现，在一个耐甲氧西林的S。在实验室制备的sciuri中，mecA同源物通过引入启动子的-10共有区的点突变转化为抗生素抗性基因，并且S.当将sciuri mecA导入敏感的沙门氏菌菌株中时，sciuri mecA可以表达显著程度的甲氧西林抗性。金黄色。我们现在证明，在这个系统中，在抗生素压力下，至少有两种不同的机制可以实现耐药表型的进一步增加。其中第一个涉及在S. sciuri-derived mecA决定簇，导致保守的SXXK基序下游的天冬酰胺被苏氨酸残基取代，这导致由S.松鼠mecA同源物。引起甲氧西林耐药性增加的第二种不同机制与沙门氏菌遗传背景中未知性质的突变有关。金黄色宿主。
A close homologue of the mecA gene, the primary drug resistance determinant in methicillin resistant Staphylococcus aureus (MRSA), is ubiquitous in the animal commensal species Staphylococcus sciuri, yet most isolates of this staphylococcal species are susceptible to beta-lactam antibiotics including methicillin. Recently, we showed that in a methicillin-resistant mutant of S. sciuri prepared in the laboratory, the mecA homologue is converted to an antibiotic resistance gene by a point mutation introduced into the -10 consensus of the promoter and such promoter-up mutants of the S. sciuri mecA can express a significant degree of methicillin resistance when introduced into an antibiotic-susceptible strain of S. aureus. We now demonstrate that in this system further increase of the drug resistance phenotype may be achieved under antibiotic pressure by at least two different mechanisms. The first one of these involves the introduction of a point mutation at nucleotide Nt1889 in the coding region of the S. sciuri-derived mecA determinant, resulting in the replacement of an asparagine with a threonine residue downstream of the conserved SXXK motif which causes extensive reduction in the beta-lactam antibiotic binding capacity (affinity) of the penicillin binding protein (PBP) encoded by the S. sciuri mecA homologue. A second, distinct, mechanism causing increased methicillin resistance is associated with mutation(s) of unknown nature in the genetic background of the S. aureus host.