Resistance to Multiple Fluoroquinolones in a Strain of Streptococcus pyogenes: D

从一名18岁的乔布斯综合征患者的血液中分离出一株化脓性葡萄球菌（NIH-R 01-GAS），该患者最近接受了包括左氧氟沙星在内的各种抗生素治疗。药敏试验显示该分离株对氟喹诺酮类抗生素耐药。拓扑异构酶parC亚基和DNA促旋酶A的喹诺酮耐药决定区（QRDRs）在属于不同属的许多细菌中是保守的。我们设计了位于这两个基因QRDRs侧翼的PCR引物。根据S. pneumoniae、E. coli和S.金黄色。从S.化脓性链球菌中的这两个基因的相同区域显示出显著高的同源性。肺炎。与敏感菌株相比，耐喹诺酮的S。化脓性链球菌DNA促旋酶A和拓扑异构酶IV的parC亚基存在点突变。最近，我们获得了另一株临床分离的S。化脓性链球菌（NIH-R 02-GAS）对某些氟喹诺酮类抗生素的MIC增加。该分离株的ParC和GyrA的氨基酸序列显示与第一分离株的点突变仅略有不同，ParC的丝氨酸-79变为丙氨酸而不是酪氨酸，并且GyrA的丝氨酸-81没有突变。两个分离株的GyrA基因均发生了蛋氨酸-99突变为亮氨酸的突变。我们认为NIH-R 02-GAS菌株中gyrA基因点突变的微小变化和parC基因罕见点突变可能解释了这两种分离株中氟喹诺酮类药物敏感性的显著差异。化脓将对其他区域进行测序。

A strain of Staphylococcus pyogenes (NIH-R01-GAS) was isolated from the blood of an 18-year-old patient with Jobs syndrome who had recently received various antibiotic treatments including levofloxacin. Susceptibility testing revealed the isolate was resistant to the fluoroquinolone antibiotics. Quinolone resistance-determining regions (QRDRs) of both the parC subunit of topoisomerase and DNA gyrase A are conserved in a number of bacteria belonging to different genera. We designed polymerase chain reaction (PCR) primers flanking the QRDRs of these two genes from S. pyogenes on the basis of the amino acid sequence homologies among S. pneumoniae, E. coli, and S. aureus. The amino acid sequences deduced from the amplified gene products from S. pyogenes demonstrated significantly high homology to the same regions of these two genes in S. pneumoniae. Compared with the quinolone-sensitive ATCC strain, the quinolone-resistant isolate of S. pyogenes presented point mutations in DNA gyrase A and in the parC subunit of topoisomerase IV. Recently, we acquired another clinical strain of S. pyogenes (NIH-R02-GAS) with increased MICs to some of the fluoroquinolone antibiotics. Amino acid sequences of ParC and GyrA of this isolate demonstrated point mutations only slightly different from those of the first isolate, with serine-79 of the ParC changed to alanine rather than tyrosine, and no mutation of serine-81 of GyrA. Mutation of methionine-99 to leucine was common to GyrA of both isolates. We propose that the minor change in point mutations in the gyrA and uncommon point mutation in the parC gene in strain NIH-R02-GAS may explain the striking differences in fluoroquinolone susceptibilities in these two isolates of S. pyogenes. Sequencing of other regions will be performed.