{"title":"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。","authors":"Takeaki Wajima, Tomokazu Ando, Emi Tanaka, Kei-Ichi Uchiya","doi":"10.1089/mdr.2025.0013","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>Haemophilus influenzae</i> clinical isolates from Japan, as information on such resistance remains limited. A total of 79 <i>H. influenzae</i> 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 <i>folA</i> fragments, indicating that FolA mediates SXT resistance in <i>H. influenzae</i>. 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 <i>H. influenzae</i> 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.</p>","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sulfamethoxazole-Trimethoprim Resistance in <i>Haemophilus influenzae</i> Clinical Isolates in Japan: Role of FolA and Horizontal Transfer.\",\"authors\":\"Takeaki Wajima, Tomokazu Ando, Emi Tanaka, Kei-Ichi Uchiya\",\"doi\":\"10.1089/mdr.2025.0013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>Haemophilus influenzae</i> clinical isolates from Japan, as information on such resistance remains limited. A total of 79 <i>H. influenzae</i> 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 <i>folA</i> fragments, indicating that FolA mediates SXT resistance in <i>H. influenzae</i>. 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 <i>H. influenzae</i> 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.</p>\",\"PeriodicalId\":18701,\"journal\":{\"name\":\"Microbial drug resistance\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-06-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbial drug resistance\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/mdr.2025.0013\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbial drug resistance","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/mdr.2025.0013","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
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.
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.