日本流感嗜血杆菌临床分离株对磺胺甲恶唑-甲氧苄啶的耐药性:叶酸和水平转移的作用。

IF 2.3 4区 医学 Q3 INFECTIOUS DISEASES
Takeaki Wajima, Tomokazu Ando, Emi Tanaka, Kei-Ichi Uchiya
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引用次数: 0

摘要

磺胺甲恶唑-甲氧苄啶(SXT)是治疗多种细菌感染的重要经验性药物。在这项研究中,我们的目的是阐明来自日本的流感嗜血杆菌临床分离株对SXT耐药的机制,因为关于这种耐药的信息仍然有限。对2018年和2022年收集的79株流感嗜血杆菌临床分离株进行分析。2018年和2022年的耐药率分别为38.7%和35.3%。多位点序列分型分析显示,ST422是最常见的序列型(36.7%),其次是ST107(26.7%)。利用基因组DNA或pcr扩增片段进行的水平转移试验显示,sst抗性通过基因组DNA和pcr扩增的folA片段转移到易感分离株,表明folA介导流感嗜血杆菌对sst的抗性。定点突变表明,异亮氨酸在FolA中95位的取代与sst抗性有关。所有耐sst菌株在FolA的第95位都有氨基酸取代:30株中有26株为亮氨酸,3株为缬氨酸,1株为甘氨酸。我们的研究结果表明,流感嗜血杆菌对SXT的耐药性是普遍存在的,并且可以通过水平转移传播。此外,FolA第95位的氨基酸取代在赋予抗性方面发挥了关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sulfamethoxazole-Trimethoprim Resistance in Haemophilus influenzae Clinical Isolates in Japan: Role of FolA and Horizontal Transfer.

Sulfamethoxazole-trimethoprim (SXT) is an important empirical treatment agent against various bacterial infections. In this study, we aimed to elucidate the mechanisms underlying SXT resistance in Haemophilus influenzae clinical isolates from Japan, as information on such resistance remains limited. A total of 79 H. influenzae clinical isolates collected in 2018 and 2022 were analyzed. The SXT resistance rates were 38.7% in 2018 and 35.3% in 2022. Multilocus sequence typing analysis revealed that ST422 was the most common sequence type (36.7%), followed by ST107 (26.7%). Horizontal transfer assays using the genomic DNA or PCR-amplified fragments revealed that SXT resistance was transferred to the susceptible isolates via genomic DNA and PCR-amplified folA fragments, indicating that FolA mediates SXT resistance in H. influenzae. Site-directed mutagenesis revealed that the substitution of isoleucine at position 95 in FolA was associated with SXT resistance. All SXT-resistant isolates had an amino acid substitution at position 95 in FolA: leucine in 26 of the 30 strains, valine in 3 strains, and glycine in 1 strain. Our findings demonstrate that SXT resistance in H. influenzae was prevalent and can spread via horizontal transfer. Furthermore, an amino acid substitution at position 95 of FolA played a key role in conferring resistance.

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来源期刊
Microbial drug resistance
Microbial drug resistance 医学-传染病学
CiteScore
6.00
自引率
3.80%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Microbial Drug Resistance (MDR) is an international, peer-reviewed journal that covers the global spread and threat of multi-drug resistant clones of major pathogens that are widely documented in hospitals and the scientific community. The Journal addresses the serious challenges of trying to decipher the molecular mechanisms of drug resistance. MDR provides a multidisciplinary forum for peer-reviewed original publications as well as topical reviews and special reports. MDR coverage includes: Molecular biology of resistance mechanisms Virulence genes and disease Molecular epidemiology Drug design Infection control.
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