Lgt a 脂蛋白分选酶和 23S rRNA 的突变作为评估幽门螺杆菌甲硝唑和克拉霉素耐药菌株的候选特征

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2024-06-18 DOI:10.1016/j.genrep.2024.101953

Atena Abedi Maghami , Amir Emami , Mohammad Reza Fattahi , Jalal Mardaneh , Neda Pirbonyeh , Abdullah Bazargani

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引用次数: 0

摘要

背景幽门螺杆菌根除方案中广泛使用的化合物存在缺陷，主要是在克拉霉素和甲硝唑MDRs模式持续存在的社区中，这是分子药物治疗修正所关注的关键标准。23S rRNA 突变是克拉霉素疗效不佳的主要原因，Lgt、RdxA 初步终止密码子格式导致甲硝唑活性降低。本研究深入分析了联合疗法中常用化合物的表型耐药性模式，并确定了主要的 MDR 模式。对 NL: 1939-2380 的 23S rRNA 进行扩增和测序。通过 PCR 测序，对 Lgt 及其邻近基因 rdxA（NL：561-1666）进行标记以提取核苷酸错配。除 MICs 外，对 Mzt、Cam、Amx 和 Tet 的耐药率分别为 42.85%、19.04%、7.14% 和 4.76%。对 MDRs 的评估结果显示，9/42（21.42%）的患者对甲硝唑和克拉霉素产生了相关形式的 MDRs，占 8/42（19.04%），而甲硝唑和阿莫西林的 MDRs 则最少。根据标记序列，2/8（25%）的 Cam 耐药患者可分离出 A2142G 和 G2097A 突变。在 Mzt 方面，7/18（38.88%）的耐药患者检测到 808-919 处的 lgt 突变，传播的 Lgt 编码位点为 233-242，p = 0.006；3/18（16.66%）的患者检测到 211（495）和 205（489）处的 rdxA 终止密码子。总体而言，在 8 个甲硝唑相关 MDR 中的 5 个（62.5%）中，在 Mzt 完全耐药水平中检测到了 lgt 突变或突变 Lgt 残基的积累，Odds Ratios：37.3.结论据推测，导致Lgt终止位点的lgt内部突变可促进甲硝唑耐药患者的探查，并与具有甲硝唑耐药中心性的强效MDR有关。

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Mutations inside Lgt a Lipoprotein sorting enzyme and 23S rRNA as the candidate signatures in the evaluation of H. pylori Metronidazole and Clarithromycin MDR strains

Background

Repute in the widely-used compounds in H. pylori eradication regimen, mainly in the communities sustained with the pattern of Clarithromycin and Metronidazole MDRs, are the critical criterias focused on in molecular medication for therapeutic revision. 23S rRNA mutations are the leading cause of Clarithromycin suboptimal efficacy, and Lgt, RdxA preliminary stop codon formats result in Metronidazole lesser activity. In the present study, phenotypic resistance patterns of commonly used compounds in combination therapy, as well as identify predominant MDR patterns, were deeply analyzed.

Methods

Columbia blood agar was used for MICs evaluation of Mzt, Cam, Amx, and Tet. 23S rRNA at NL: 1939‐2380 was amplified and sequenced. Lgt and its neighboring gene rdxA at NL: 561‐1666 were tagged to extract nucleotide mismatches by PCR-sequencing.

Results

In total, 42 out of 348 (12.06%) were found to have H. pylori related disease. Beyond the MICs, resistance rates to Mzt, Cam, Amx, and Tet were 42.85%, 19.04%, 7.14%, 4.76%. Quote of MDRs, evaluated patients with a rate of 9/42 (21.42%); relevant forms of MDRs were the pattern of Metronidazole and Clarithromycin for 8/42 (19.04%), while Metronidazole and Amoxicillin MDRs addressed a minimum. Given the tagged sequences, 2/8 (25%) of Cam-resistant patients could be isolated with the mutations A2142G and G2097A. For Mzt, 7/18 (38.88%) of resistant patients detected by lgt mutations at 808‐919, disseminated with Lgt coding site at 233‐242, p = 0.006. rdxA stop codons at 211 (495) and 205 (489) detected in 3/18 (16.66%). Overall, within 5 out of 8 (62.5%) Metronidazole-associated MDRs, accumulation of lgt mutations or mutated Lgt residues was impressively detected in Mzt full level of resistance, Odds Ratios: 37.3.

Conclusions

It is assumed that mutations inside lgt that caused Lgt termination sites can facilitate Metronidazole-resistant patient probing and be related to potent MDRs with Metronidazole resistance centrality.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.