Pub Date : 2026-01-01DOI: 10.1016/j.jgar.2025.12.005
Tuelo Mogashoa , Justice T. Ngom , Johannes Loubser , Kedumetse Seru , Tuduetso Molefi , One Stephen , Rosemary M. Musonda , Simani Gaseitsiwe , Robin M. Warren , Anzaan Dippenaar , Elizabeth M. Streicher , Sikhulile Moyo
Background
Undetected rifampicin resistance is a threat to global tuberculosis (TB) control efforts by delaying effective treatment. In different studies, non-canonical rpoB mutations outside the rifampicin resistance-determining region have been reported at varying prevalences by country. Here, we report cases of rifampicin resistance in Botswana that were missed by the routine molecular diagnostic assays.
Methods
Individuals were tested under routine programme conditions, in accordance with national guidelines, at four designated drug-resistant TB clinics from 2017 to 2022. Initial testing at the facilities included GeneXpert MTB/RIF ultra and later phenotypic drug susceptibility testing (pDST), as well as the Hain MTBDRsl line probe assay, at the National Tuberculosis Reference Laboratory. A total of nine isolates were subsequently sequenced on the Illumina NextSeq 2000 instrument.
Results
At the point of care, routine molecular tests classified all nine individuals as susceptible to rifampicin. Subsequent culture and phenotypic drug susceptibility testing confirmed rifampicin resistance. Whole-genome sequencing identified non-canonical rpoB mutations outside the rifampicin resistance-determining region I49F and V170F, which are associated with low-level rifampicin resistance. Of the nine isolates sequenced, 4 (44%) harboured the rpoB V170F mutation, while 5 (56%) harboured the rpoB I491F mutation.
Conclusions
These results highlight a diagnostic gap within the current algorithms and show the value of sequencing-based approaches for accurately detecting drug resistance. Incorporating sequencing into routine clinical practice could help guide the selection of TB treatment and improve treatment outcomes in patients who do not respond to first-line therapy.
{"title":"Undetected rifampicin-resistant tuberculosis associated with rpoB I491F and V170F mutations in Botswana: Diagnostic implications","authors":"Tuelo Mogashoa , Justice T. Ngom , Johannes Loubser , Kedumetse Seru , Tuduetso Molefi , One Stephen , Rosemary M. Musonda , Simani Gaseitsiwe , Robin M. Warren , Anzaan Dippenaar , Elizabeth M. Streicher , Sikhulile Moyo","doi":"10.1016/j.jgar.2025.12.005","DOIUrl":"10.1016/j.jgar.2025.12.005","url":null,"abstract":"<div><h3>Background</h3><div>Undetected rifampicin resistance is a threat to global tuberculosis (TB) control efforts by delaying effective treatment. In different studies, non-canonical <em>rpoB</em> mutations outside the rifampicin resistance-determining region have been reported at varying prevalences by country. Here, we report cases of rifampicin resistance in Botswana that were missed by the routine molecular diagnostic assays.</div></div><div><h3>Methods</h3><div>Individuals were tested under routine programme conditions, in accordance with national guidelines, at four designated drug-resistant TB clinics from 2017 to 2022. Initial testing at the facilities included GeneXpert MTB/RIF ultra and later phenotypic drug susceptibility testing (pDST), as well as the Hain MTBDR<em>sl</em> line probe assay, at the National Tuberculosis Reference Laboratory. A total of nine isolates were subsequently sequenced on the Illumina NextSeq 2000 instrument.</div></div><div><h3>Results</h3><div>At the point of care, routine molecular tests classified all nine individuals as susceptible to rifampicin. Subsequent culture and phenotypic drug susceptibility testing confirmed rifampicin resistance. Whole-genome sequencing identified non-canonical <em>rpoB</em> mutations outside the rifampicin resistance-determining region I49F and V170F, which are associated with low-level rifampicin resistance. Of the nine isolates sequenced, 4 (44%) harboured the <em>rpoB</em> V170F mutation, while 5 (56%) harboured the <em>rpoB</em> I491F mutation.</div></div><div><h3>Conclusions</h3><div>These results highlight a diagnostic gap within the current algorithms and show the value of sequencing-based approaches for accurately detecting drug resistance. Incorporating sequencing into routine clinical practice could help guide the selection of TB treatment and improve treatment outcomes in patients who do not respond to first-line therapy.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 171-174"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The use of antibiotics may facilitate the colonisation of antimicrobial-resistant organisms and genes within the host microbiome. However, studies on the effects of antibiotics on microbiomes and resistomes in clinical settings are limited.
Aim
The aim of this study was to determine the effects of antibiotic prophylaxis during colorectal cancer surgery on the oral and gut microbiomes and resistomes of patients.
Methods
We conducted a single-centre prospective observational cohort study on patients who underwent colorectal cancer surgery with antibiotic prophylaxis. DNA was extracted from oral and stool samples 1 day prior to the procedure and on postoperative days 1, 7, and 28. Subsequently, metagenomic sequencing was performed.
Findings
Among the eight patients with colorectal cancer, α-diversity in the oral and stool samples significantly decreased from baseline to each of the three post-administration time points. The abundance of anaerobic genera significantly decreased from baseline to Day 7. In the stool samples, Enterococcus, Limosilactobacillus, and Lacticaseibacillus abundances were markedly increased. Total antibiotic resistance gene (ARG) abundance significantly increased from the baseline to Day 7 in both oral and stool samples. The impact of the increase observed on Day 7 decreased but still persisted until Day 28 for diversity and total abundance of ARGs.
Conclusions
Oral and gut microbiomes and resistomes exhibited marked alterations that gradually reversed over time. Changes in the microbiome were associated with the spectrum of antibiotics used.
{"title":"Impact of antimicrobial prophylaxis in colorectal cancer surgery on the gut and oral microbiome and resistome: A prospective observational cohort study","authors":"Hiroki Kitagawa , Toshiki Kajihara , Koji Yahara , Norikazu Kitamura , Norifumi Shigemoto , Hirofumi Doi , Kensuke Shimbara , Kosuke Yoshimura , Ikki Nakashima , Shinnosuke Uegami , Yusuke Watadani , Miki Kawada-Matsuo , Hitoshi Komatsuzawa , Hiroki Ohge , Motoyuki Sugai","doi":"10.1016/j.jgar.2025.12.014","DOIUrl":"10.1016/j.jgar.2025.12.014","url":null,"abstract":"<div><h3>Background</h3><div>The use of antibiotics may facilitate the colonisation of antimicrobial-resistant organisms and genes within the host microbiome. However<strong>,</strong> studies on the effects of antibiotics on microbiomes and resistomes in clinical settings are limited.</div></div><div><h3>Aim</h3><div>The aim of this study was to determine the effects of antibiotic prophylaxis during colorectal cancer surgery on the oral and gut microbiomes and resistomes of patients.</div></div><div><h3>Methods</h3><div>We conducted a single-centre prospective observational cohort study on patients who underwent colorectal cancer surgery with antibiotic prophylaxis. DNA was extracted from oral and stool samples 1 day prior to the procedure and on postoperative days 1, 7, and 28. Subsequently, metagenomic sequencing was performed.</div></div><div><h3>Findings</h3><div>Among the eight patients with colorectal cancer, α-diversity in the oral and stool samples significantly decreased from baseline to each of the three post-administration time points. The abundance of anaerobic genera significantly decreased from baseline to Day 7. In the stool samples, <em>Enterococcus, Limosilactobacillus</em>, and <em>Lacticaseibacillus</em> abundances were markedly increased. Total antibiotic resistance gene (ARG) abundance significantly increased from the baseline to Day 7 in both oral and stool samples. The impact of the increase observed on Day 7 decreased but still persisted until Day 28 for diversity and total abundance of ARGs.</div></div><div><h3>Conclusions</h3><div>Oral and gut microbiomes and resistomes exhibited marked alterations that gradually reversed over time. Changes in the microbiome were associated with the spectrum of antibiotics used.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 227-234"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.jgar.2025.12.006
Maiko Kirikae , Satomi Takei , Thi Thi Htoon , Pan Ei Soe , Nang Sarm Hom , San Yu Maw , May Yee Aung , Shino Hosoya , Swe Setk , Htay Htay Tin , Yuki Uehara , Teruo Kirikae , Tatsuya Tada
Objectives
Tigecycline is one of the last-resort antibiotics for treating serious infections caused by multidrug-resistant pathogens. This is the first report of clinical isolates of tigecycline-resistant Escherichia coli harbouring tet(X4) in Myanmar.
Methods
Two E. coli isolates were obtained from two patients at two hospitals in Myanmar from November 2023 to May 2024. They were identified using MALDI-TOF MS, and minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Genomic DNA was extracted and sequenced using next generation sequencing. Drug resistance factors were determined, and the genetic environments surrounding tet(X4) and blaNDM-5 were analysed. Conjugation rates of plasmids harbouring tet(X4) and blaNDM-5 were calculated.
Results
One strain, TGH62, was resistant to tigecycline (MIC 8 µg/mL) and meropenem (MIC 128 µg/mL), whereas the other, YGH433, was resistant to tigecycline (MIC 4 µg/mL). Whole-genome sequencing revealed that both strains harboured tet(X4) on plasmids and TGH62 also harboured blaNDM-5 on a plasmid. The plasmids carrying tet(X4) in TGH62 and YGH433 belonged to the IncI and IncFII incompatibility groups, respectively. The plasmid carrying blaNDM-5 belonged to the IncFIA incompatibility group. The conjugation efficiencies of the plasmids harbouring tet(X4) in YGH433 and blaNDM-5 in TGH62 were relatively high, whereas that harbouring tet(X4) in TGH62 was low.
Conclusions
Tigecycline-resistant Enterobacteriaceae harbouring tet(X4) may spread in hospitals in Myanmar. Further studies are needed to detect tet(X4) conferring tigecycline resistance in hospitals as well as environmental settings in Myanmar.
{"title":"Detection of clinical isolates of tigecycline-resistant Escherichia coli harbouring tet(X4) in Myanmar","authors":"Maiko Kirikae , Satomi Takei , Thi Thi Htoon , Pan Ei Soe , Nang Sarm Hom , San Yu Maw , May Yee Aung , Shino Hosoya , Swe Setk , Htay Htay Tin , Yuki Uehara , Teruo Kirikae , Tatsuya Tada","doi":"10.1016/j.jgar.2025.12.006","DOIUrl":"10.1016/j.jgar.2025.12.006","url":null,"abstract":"<div><h3>Objectives</h3><div>Tigecycline is one of the last-resort antibiotics for treating serious infections caused by multidrug-resistant pathogens. This is the first report of clinical isolates of tigecycline-resistant <em>Escherichia coli</em> harbouring <em>tet</em>(X4) in Myanmar.</div></div><div><h3>Methods</h3><div>Two <em>E. coli</em> isolates were obtained from two patients at two hospitals in Myanmar from November 2023 to May 2024. They were identified using MALDI-TOF MS, and minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Genomic DNA was extracted and sequenced using next generation sequencing. Drug resistance factors were determined, and the genetic environments surrounding <em>tet</em>(X4) and <em>bla</em><sub>NDM-5</sub> were analysed. Conjugation rates of plasmids harbouring <em>tet</em>(X4) and <em>bla</em><sub>NDM-5</sub> were calculated.</div></div><div><h3>Results</h3><div>One strain, TGH62, was resistant to tigecycline (MIC 8 µg/mL) and meropenem (MIC 128 µg/mL), whereas the other, YGH433, was resistant to tigecycline (MIC 4 µg/mL). Whole-genome sequencing revealed that both strains harboured <em>tet</em>(X4) on plasmids and TGH62 also harboured <em>bla</em><sub>NDM-5</sub> on a plasmid. The plasmids carrying <em>tet</em>(X4) in TGH62 and YGH433 belonged to the IncI and IncFII incompatibility groups, respectively. The plasmid carrying <em>bla</em><sub>NDM-5</sub> belonged to the IncFIA incompatibility group. The conjugation efficiencies of the plasmids harbouring <em>tet</em>(X4) in YGH433 and <em>bla</em><sub>NDM-5</sub> in TGH62 were relatively high, whereas that harbouring <em>tet</em>(X4) in TGH62 was low.</div></div><div><h3>Conclusions</h3><div>Tigecycline-resistant <em>Enterobacteriaceae</em> harbouring <em>tet</em>(X4) may spread in hospitals in Myanmar. Further studies are needed to detect <em>tet</em>(X4) conferring tigecycline resistance in hospitals as well as environmental settings in Myanmar.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 235-240"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.jgar.2025.12.011
Melina Rapoport , Nahir Gattoni , Celeste Lucero , Juan Manuel de Mendieta
Objective
This study describes the phenotypic, molecular, and genomic characterisation of emerging blaNDM-1-producing Pseudomonas aeruginosa in Argentina, mainly driven by ST308 and ST274 clones.
Methods
Nineteen clinical isolates submitted to the National and Regional Reference Laboratory on Antimicrobial Resistance between 2018 and 2024 from nine hospitals were analysed. Antimicrobial susceptibility and carbapenemase activity were evaluated. In-house PCR assays were used to detect relevant resistance determinants. Genetic relatedness was assessed by SpeI-PFGE, and whole-genome sequencing was performed on nine isolates using Illumina and Oxford Nanopore technologies.
Results
All isolates were resistant to all β-lactams tested, except two, M28149 and M28715, that remained susceptible to aztreonam. All carried blaNDM-1. PFGE identified six pulsotypes, with 13 isolates in one dominant type. Whole-genome sequencing revealed six ST308, two ST274, and one ST3243; five ST308 isolates also harboured the rmtD 16S methylase gene. Phylogenetic analysis of ST308 isolates showed they formed a distinct cluster compared with those from other countries.
Conclusions
The emergence of blaNDM-1-producing P. aeruginosa associated with ST308 and ST274 clones represents a public health concern, particularly given the scarcity of effective treatment options for severe infections caused by these high-risk clones.
{"title":"Dissemination of NDM-1-producing Pseudomonas aeruginosa ST308 and ST274 high-risk clones in Argentina","authors":"Melina Rapoport , Nahir Gattoni , Celeste Lucero , Juan Manuel de Mendieta","doi":"10.1016/j.jgar.2025.12.011","DOIUrl":"10.1016/j.jgar.2025.12.011","url":null,"abstract":"<div><h3>Objective</h3><div>This study describes the phenotypic, molecular, and genomic characterisation of emerging <em>bla</em><sub>NDM-1</sub>-producing <em>Pseudomonas aeruginosa</em> in Argentina, mainly driven by ST308 and ST274 clones.</div></div><div><h3>Methods</h3><div>Nineteen clinical isolates submitted to the National and Regional Reference Laboratory on Antimicrobial Resistance between 2018 and 2024 from nine hospitals were analysed. Antimicrobial susceptibility and carbapenemase activity were evaluated. In-house PCR assays were used to detect relevant resistance determinants. Genetic relatedness was assessed by SpeI-PFGE, and whole-genome sequencing was performed on nine isolates using Illumina and Oxford Nanopore technologies.</div></div><div><h3>Results</h3><div>All isolates were resistant to all β-lactams tested, except two, M28149 and M28715, that remained susceptible to aztreonam. All carried <em>bla</em><sub>NDM-1</sub>. PFGE identified six pulsotypes, with 13 isolates in one dominant type. Whole-genome sequencing revealed six ST308, two ST274, and one ST3243; five ST308 isolates also harboured the <em>rmtD</em> 16S methylase gene. Phylogenetic analysis of ST308 isolates showed they formed a distinct cluster compared with those from other countries.</div></div><div><h3>Conclusions</h3><div>The emergence of <em>bla</em><sub>NDM-1</sub>-producing <em>P. aeruginosa</em> associated with ST308 and ST274 clones represents a public health concern, particularly given the scarcity of effective treatment options for severe infections caused by these high-risk clones.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 187-194"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.jgar.2025.12.016
Dapeng Fan, Hao Li, Xuechai Shang, Miaofen Yang, Huanyu Li, Yongning Yue, Long Cai
Objective
To evaluate the diagnostic performance of the InnowaveDx MTB/RIF/INH assay for the simultaneous detection of Mycobacterium tuberculosis and resistance to rifampicin and isoniazid.
Methods
We evaluated the performance of the InnowaveDx MTB/RIF/INH (InnowaveDx) assay in diagnosing pulmonary tuberculosis and detecting rifampicin and isoniazid resistance at the Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine.
Results
Using the clinical final diagnosis as the standard, the sensitivity of InnowaveDx was 68.0%, which was higher than that of acid-fast bacilli smear, MGIT culture, and Xpert (P < .001). The specificity was 97.1%, which was higher than acid-fast bacilli smear (P < .001). The agreement between InnowaveDx and MGIT phenotypic drug sensitivity, as well as Xpert, for detecting rifampicin resistance, had kappa values of 0.783 and 0.940, respectively. The agreement between InnowaveDx and MGIT phenotypic drug sensitivity, as well as multicolor melting curve analysis, for detecting isoniazid resistance, had kappa values of 0.915 and 1. The discrepancies in rifampicin- and isoniazid-resistance detection were observed in 11 and 4 cases, respectively.
Conclusions
The InnowaveDx MTB/RIF/INH assay demonstrates good performance in detecting M. tuberculosis as well as rifampicin and isoniazid resistance. The discrepancies in rifampicin-resistance results and phenotypic resistance are mainly the result of borderline resistance mutations.
{"title":"Evaluating the performance of the InnowaveDx MTB/RIF/INH for simultaneous detection of Mycobacterium tuberculosis and resistance to rifampicin and isoniazid","authors":"Dapeng Fan, Hao Li, Xuechai Shang, Miaofen Yang, Huanyu Li, Yongning Yue, Long Cai","doi":"10.1016/j.jgar.2025.12.016","DOIUrl":"10.1016/j.jgar.2025.12.016","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the diagnostic performance of the InnowaveDx MTB/RIF/INH assay for the simultaneous detection of Mycobacterium tuberculosis and resistance to rifampicin and isoniazid.</div></div><div><h3>Methods</h3><div>We evaluated the performance of the InnowaveDx MTB/RIF/INH (InnowaveDx) assay in diagnosing pulmonary tuberculosis and detecting rifampicin and isoniazid resistance at the Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine.</div></div><div><h3>Results</h3><div>Using the clinical final diagnosis as the standard, the sensitivity of InnowaveDx was 68.0%, which was higher than that of acid-fast bacilli smear, MGIT culture, and Xpert (<em>P</em> < .001). The specificity was 97.1%, which was higher than acid-fast bacilli smear (<em>P</em> < .001). The agreement between InnowaveDx and MGIT phenotypic drug sensitivity, as well as Xpert, for detecting rifampicin resistance, had <em>kappa</em> values of 0.783 and 0.940, respectively. The agreement between InnowaveDx and MGIT phenotypic drug sensitivity, as well as multicolor melting curve analysis, for detecting isoniazid resistance, had <em>kappa</em> values of 0.915 and 1. The discrepancies in rifampicin- and isoniazid-resistance detection were observed in 11 and 4 cases, respectively.</div></div><div><h3>Conclusions</h3><div>The InnowaveDx MTB/RIF/INH assay demonstrates good performance in detecting <em>M. tuberculosis</em> as well as rifampicin and isoniazid resistance. The discrepancies in rifampicin-resistance results and phenotypic resistance are mainly the result of borderline resistance mutations.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 246-253"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.jgar.2025.12.009
Jee Hong KIM , Hyunkeun KIM , Kwan Soo KO
Objective
DNA methylation, catalysed by DNA methyltransferases (MTases), plays a crucial role in bacterial physiology. In this study, we investigated the effects of the DNA MTases, DNA adenine methyltransferase (Dam) and DNA cytosine methyltransferase (Dcm), on bacterial fitness and mutation rates in Escherichia coli.
Methods
We constructed an E. coli K-12 MG1655 strain lacking both the dam and dcm genes (ΔdamΔdcm). The bacterial fitness was assessed using growth curves and competition assays. Antibiotic susceptibility and persister cell formation were also evaluated. Additionally, the spontaneous mutation rates and mutation types in response to rifampicin and colistin were analysed.
Results
The MTase-deficient mutant ΔdamΔdcm exhibited significantly reduced growth rates and competitiveness compared to the wild-type (WT) strain. However, no significant differences in antibiotic resistance or persister cell formation rates were observed between the mutant and WT strains. Mutation frequencies in ΔdamΔdcm were significantly higher than in the WT when exposed to both rifampicin and colistin. Furthermore, a higher ratio of transition mutations in the rpoB and pmrAB genes was observed in rifampicin-resistant and colistin-resistant colonies derived from ΔdamΔdcm, respectively. DNA methylation influences bacterial growth and competitiveness, and the absence of MTases leads to increased spontaneous mutation rates under antibiotic pressure.
Conclusions
These findings suggest that DNA methylation plays a critical role in maintaining genomic stability and contributing to the development of antibiotic resistance.
{"title":"Impact of DNA methyltransferases on bacterial fitness and genome stability in Escherichia coli","authors":"Jee Hong KIM , Hyunkeun KIM , Kwan Soo KO","doi":"10.1016/j.jgar.2025.12.009","DOIUrl":"10.1016/j.jgar.2025.12.009","url":null,"abstract":"<div><h3>Objective</h3><div>DNA methylation, catalysed by DNA methyltransferases (MTases), plays a crucial role in bacterial physiology. In this study, we investigated the effects of the DNA MTases, DNA adenine methyltransferase (Dam) and DNA cytosine methyltransferase (Dcm), on bacterial fitness and mutation rates in <em>Escherichia coli.</em></div></div><div><h3>Methods</h3><div>We constructed an <em>E. coli</em> K-12 MG1655 strain lacking both the <em>dam</em> and <em>dcm</em> genes (Δ<em>dam</em>Δ<em>dcm</em>). The bacterial fitness was assessed using growth curves and competition assays. Antibiotic susceptibility and persister cell formation were also evaluated. Additionally, the spontaneous mutation rates and mutation types in response to rifampicin and colistin were analysed.</div></div><div><h3>Results</h3><div>The MTase-deficient mutant Δ<em>dam</em>Δ<em>dcm</em> exhibited significantly reduced growth rates and competitiveness compared to the wild-type (WT) strain. However, no significant differences in antibiotic resistance or persister cell formation rates were observed between the mutant and WT strains. Mutation frequencies in Δ<em>dam</em>Δ<em>dcm</em> were significantly higher than in the WT when exposed to both rifampicin and colistin. Furthermore, a higher ratio of transition mutations in the <em>rpoB</em> and <em>pmrAB</em> genes was observed in rifampicin-resistant and colistin-resistant colonies derived from Δ<em>dam</em>Δ<em>dcm</em>, respectively. DNA methylation influences bacterial growth and competitiveness, and the absence of MTases leads to increased spontaneous mutation rates under antibiotic pressure.</div></div><div><h3>Conclusions</h3><div>These findings suggest that DNA methylation plays a critical role in maintaining genomic stability and contributing to the development of antibiotic resistance.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 203-208"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.jgar.2025.12.015
Xiang-Dong Wang , Dongmei Niu , Wei Lv , Lei Wang , Chen-Yu Zhang , Chunni Zhang , Jiaxi Song , Xueling Hu , Cheng Wang
Objective
Circulating non-coding small RNAs (sRNAs) have recently emerged as promising biomarkers for Mycobacterium tuberculosis (Mtb). However, little is known about the expression patterns and combined diagnostic potential of M. tuberculosis-derived sRNA (TB-sRNA) and endogenous miRNA in the circulation of patients with multidrug-resistant tuberculosis (MDR-TB).
Methods
Illumina sequencing by synthesis technology and quantitative real-time polymerase chain reaction were used to identify TB-sRNAs in serum and sputum from patients infected with drug-resistant TB, drug-sensitive TB (DS-TB), and controls. Simultaneously, four endogenous miRNAs – miR-29c, miR-132, miR-320b, and miR-548e – were chosen for further study. The diagnostic performance of significantly altered sRNAs and miRNAs was analysed using receiver operating characteristic (ROC) curves.
Results
Illumina sequencing by synthesis combined with individual quantitative real-time polymerase chain reaction verification successfully identified one TB-encoded sRNA, named TB-sRNA015, and endogenous miR-132 were significantly elevated in patients with MDR-TB compared to patients with DS-TB and controls (P < 0.01). ROC analyses showed that the area under the ROC curve (AUC) for serum sRNA015 discriminating patients with MDR-TB from controls and patients with DS-TB were 0.774 (95% confidence interval [CI], 0.653–0.895) and 0.692 (95% CI, 0.560–0.825), respectively. For serum miR-132, the AUCs were 0.841 (95% CI, 0.735–0.946) for MDR-TB vs. controls and 0.655 (95% CI, 0.518–0.793) for MDR-TB vs. DS-TB. Importantly, combining sRNA015 with miR-132 increased the AUC to 0.860 (95% CI, 0.760–0.960) for discriminating MDR-TB from controls.
Conclusions
The combination of serum sRNA015 and miR-132 may serve as an auxiliary diagnostic tool for MDR-TB infection.
{"title":"A combination of Mycobacterium tuberculosis-derived sRNA and endogenous miRNA in circulation as novel auxiliary diagnostic markers for patients with multidrug-resistant tuberculosis","authors":"Xiang-Dong Wang , Dongmei Niu , Wei Lv , Lei Wang , Chen-Yu Zhang , Chunni Zhang , Jiaxi Song , Xueling Hu , Cheng Wang","doi":"10.1016/j.jgar.2025.12.015","DOIUrl":"10.1016/j.jgar.2025.12.015","url":null,"abstract":"<div><h3>Objective</h3><div>Circulating non-coding small RNAs (sRNAs) have recently emerged as promising biomarkers for <em>Mycobacterium tuberculosis</em> (Mtb). However, little is known about the expression patterns and combined diagnostic potential of <em>M. tuberculosis</em>-derived sRNA (TB-sRNA) and endogenous miRNA in the circulation of patients with multidrug-resistant tuberculosis (MDR-TB).</div></div><div><h3>Methods</h3><div>Illumina sequencing by synthesis technology and quantitative real-time polymerase chain reaction were used to identify TB-sRNAs in serum and sputum from patients infected with drug-resistant TB, drug-sensitive TB (DS-TB), and controls. Simultaneously, four endogenous miRNAs – miR-29c, miR-132, miR-320b, and miR-548e – were chosen for further study. The diagnostic performance of significantly altered sRNAs and miRNAs was analysed using receiver operating characteristic (ROC) curves.</div></div><div><h3>Results</h3><div>Illumina sequencing by synthesis combined with individual quantitative real-time polymerase chain reaction verification successfully identified one TB-encoded sRNA, named TB-sRNA015, and endogenous miR-132 were significantly elevated in patients with MDR-TB compared to patients with DS-TB and controls (<em>P</em> < 0.01). ROC analyses showed that the area under the ROC curve (AUC) for serum sRNA015 discriminating patients with MDR-TB from controls and patients with DS-TB were 0.774 (95% confidence interval [CI], 0.653–0.895) and 0.692 (95% CI, 0.560–0.825), respectively. For serum miR-132, the AUCs were 0.841 (95% CI, 0.735–0.946) for MDR-TB vs. controls and 0.655 (95% CI, 0.518–0.793) for MDR-TB vs. DS-TB. Importantly, combining sRNA015 with miR-132 increased the AUC to 0.860 (95% CI, 0.760–0.960) for discriminating MDR-TB from controls.</div></div><div><h3>Conclusions</h3><div>The combination of serum sRNA015 and miR-132 may serve as an auxiliary diagnostic tool for MDR-TB infection.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 264-272"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.jgar.2025.12.004
Muhammad Sharjeel , Memoona Irshad , Azka Rizvi , Altaf Ahmed , Muhammad Jan Leghari
Objective
Rapid identification of lower respiratory tract infection pathogens is critical for initiating early antimicrobial therapy. This study aimed at evaluating the role of multiplex polymerase chain reaction (mPCR) in detecting respiratory pathogens and antimicrobial resistance at a transplant centre.
Methods
The study was a single-centre, retrospective analysis, completed at a tertiary care transplant centre. Data were included from 242 patients admitted with lower respiratory tract infection during a 24-month period. Respiratory specimens were analysed through BioFire PCR. Blood mPCR specimens were excluded (n = 44). Multiplex PCR results were compared with the gold standard of culture and sensitivity testing.
Results
A total of 198 patients were included in the study. The majority had a history of chronic hepatic or renal impairment (n = 95; 48%) or liver/kidney transplantation (n = 57; 28.8%). Chest imaging (n = 162) predominantly revealed pleural effusions (35.2%) and parenchymal infiltrates (28.4%). Most common sample types included sputum (n = 101; 51.0%) and tracheal aspirates (n = 93; 47.0%). Standard culture detected the following pathogens: 290 typical bacteria, 2 atypical organisms, and 95 viral detections. Klebsiella pneumoniae (32.3%) and Escherichia coli (28.8%) were most frequently identified. In n = 102 patients with corresponding culture results, mPCR had sensitivity of 76% and specificity of 59%, with 66.7% concordance between methods. Multiplex PCR and culture identified multiple bacterial species in 38 (37.3%) and 17 (16.7%) cases, respectively. Antimicrobial resistance gene analysis revealed high prevalence of CTX-M (30%), NDM (28%), and OXA-48-like (22%) mutations.
Conclusions
Multiplex PCR pneumonia panel demonstrated high sensitivity in detecting respiratory pathogens but had limitations in its specificity when compared to culture methods.
{"title":"Multiplex PCR pneumonia panel compared to standard culture of respiratory specimens: Retrospective results from a transplant centre","authors":"Muhammad Sharjeel , Memoona Irshad , Azka Rizvi , Altaf Ahmed , Muhammad Jan Leghari","doi":"10.1016/j.jgar.2025.12.004","DOIUrl":"10.1016/j.jgar.2025.12.004","url":null,"abstract":"<div><h3>Objective</h3><div>Rapid identification of lower respiratory tract infection pathogens is critical for initiating early antimicrobial therapy. This study aimed at evaluating the role of multiplex polymerase chain reaction (mPCR) in detecting respiratory pathogens and antimicrobial resistance at a transplant centre.</div></div><div><h3>Methods</h3><div>The study was a single-centre, retrospective analysis, completed at a tertiary care transplant centre. Data were included from 242 patients admitted with lower respiratory tract infection during a 24-month period. Respiratory specimens were analysed through BioFire PCR. Blood mPCR specimens were excluded (<em>n</em> = 44). Multiplex PCR results were compared with the gold standard of culture and sensitivity testing.</div></div><div><h3>Results</h3><div>A total of 198 patients were included in the study. The majority had a history of chronic hepatic or renal impairment (<em>n</em> = 95; 48%) or liver/kidney transplantation (<em>n</em> = 57; 28.8%). Chest imaging (<em>n</em> = 162) predominantly revealed pleural effusions (35.2%) and parenchymal infiltrates (28.4%). Most common sample types included sputum (<em>n</em> = 101; 51.0%) and tracheal aspirates (<em>n</em> = 93; 47.0%). Standard culture detected the following pathogens: 290 typical bacteria, 2 atypical organisms, and 95 viral detections. <em>Klebsiella pneumoniae</em> (32.3%) and <em>Escherichia coli</em> (28.8%) were most frequently identified. In <em>n</em> = 102 patients with corresponding culture results, mPCR had sensitivity of 76% and specificity of 59%, with 66.7% concordance between methods. Multiplex PCR and culture identified multiple bacterial species in 38 (37.3%) and 17 (16.7%) cases, respectively. Antimicrobial resistance gene analysis revealed high prevalence of CTX-M (30%), NDM (28%), and OXA-48-like (22%) mutations.</div></div><div><h3>Conclusions</h3><div>Multiplex PCR pneumonia panel demonstrated high sensitivity in detecting respiratory pathogens but had limitations in its specificity when compared to culture methods.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 179-186"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.jgar.2025.12.008
Samara Sant’Anna de Oliveira , Camille Alves Brito de Moura , Kaylanne Montenegro , Thereza Cristina da Costa Vianna , Ana Paula Alves do Nascimento , Gerson Gatto de Azeredo Coutinho , Hosana Dau Ferreira de Souza , Claudia Gladys Flores Sejas , Alexander Machado Cardoso , Kayo Bianco , Maysa Mandetta Clementino
Objective
Uropathogenic Escherichia coli (UPEC) poses a significant public health challenge due to increasing antimicrobial resistance (AMR) and severe infections. This study aimed to investigate the genetic heterogeneity and AMR mechanisms of a clinical UPEC strain associated with a fatal healthcare-associated infection.
Methods
Whole-genome sequencing (WGS) was performed on a multidrug-resistant (MDR) UPEC strain isolated from a pediatric patient by using an Illumina Miseq platform. The genome was assembled using Unicycler v0.4.8 and was annotated using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). Genomic analysis included characterisation of the resistome, virulome, and phylogenetic profile using various bioinformatics tools such as ResFinder v4.7.2, VFDB, and PubMLST.
Results
The isolate has a genome with a size of 4,681,240 bp, a GC content of 50.60% and harbour seven plasmids. Genomic analysis revealed multiple genetic determinants contributing to a multidrug-resistant profile, including efflux systems, enzymatic target alterations, and antibiotic transporter modifications. Adhesin genes (fimH, afaA-D, lpfA, fdeC, csgA), hemolysins (hlyE, hlyF), iron acquisition systems (iucC, iutA, sitA), and genes related to antimicrobial peptide degradation (ompT, traJ) and colicin production (cma, cvaC) were identified. Resistance to heavy metals (tellurium, copper/silver, arsenic) was also detected. These findings characterise the isolate as a highly virulent, multidrug-resistant, and environmentally resilient emerging UPEC clone.
Conclusions
This study highlights the convergence of virulence, AMR, and environmental adaptability in an ST131-H30 UPEC strain. The findings underscore the critical need for comprehensive genomic surveillance, infection control strategies to mitigate the public health impact of MDR E. coli.
{"title":"Genomic insights into a multidrug-resistant uropathogenic Escherichia coli ST131-H30 strain associated with a fatal healthcare-associated infection","authors":"Samara Sant’Anna de Oliveira , Camille Alves Brito de Moura , Kaylanne Montenegro , Thereza Cristina da Costa Vianna , Ana Paula Alves do Nascimento , Gerson Gatto de Azeredo Coutinho , Hosana Dau Ferreira de Souza , Claudia Gladys Flores Sejas , Alexander Machado Cardoso , Kayo Bianco , Maysa Mandetta Clementino","doi":"10.1016/j.jgar.2025.12.008","DOIUrl":"10.1016/j.jgar.2025.12.008","url":null,"abstract":"<div><h3>Objective</h3><div>Uropathogenic Escherichia coli (UPEC) poses a significant public health challenge due to increasing antimicrobial resistance (AMR) and severe infections. This study aimed to investigate the genetic heterogeneity and AMR mechanisms of a clinical UPEC strain associated with a fatal healthcare-associated infection.</div></div><div><h3>Methods</h3><div>Whole-genome sequencing (WGS) was performed on a multidrug-resistant (MDR) UPEC strain isolated from a pediatric patient by using an Illumina Miseq platform. The genome was assembled using Unicycler v0.4.8 and was annotated using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). Genomic analysis included characterisation of the resistome, virulome, and phylogenetic profile using various bioinformatics tools such as ResFinder v4.7.2, VFDB, and PubMLST.</div></div><div><h3>Results</h3><div>The isolate has a genome with a size of 4,681,240 bp, a GC content of 50.60% and harbour seven plasmids. Genomic analysis revealed multiple genetic determinants contributing to a multidrug-resistant profile, including efflux systems, enzymatic target alterations, and antibiotic transporter modifications. Adhesin genes (fimH, afaA-D, lpfA, fdeC, csgA), hemolysins (hlyE, hlyF), iron acquisition systems (iucC, iutA, sitA), and genes related to antimicrobial peptide degradation (ompT, traJ) and colicin production (cma, cvaC) were identified. Resistance to heavy metals (tellurium, copper/silver, arsenic) was also detected. These findings characterise the isolate as a highly virulent, multidrug-resistant, and environmentally resilient emerging UPEC clone.</div></div><div><h3>Conclusions</h3><div>This study highlights the convergence of virulence, AMR, and environmental adaptability in an ST131-H30 UPEC strain. The findings underscore the critical need for comprehensive genomic surveillance, infection control strategies to mitigate the public health impact of MDR <em>E. coli.</em></div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 175-178"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Studies of carbapenem-resistant Pseudomonas aeruginosa (CRPA)-harbouring OXA-48-like carbapenemases are rare. The study aimed to report the emergence and characterization of a novel high-risk clone of CRPA-harbouring OXA-48-like from India.
Methods
Identification, AST, phenotypic detection of carbapenemases and WGS using Ion-Torrent-S5 platform were carried out. Analyses included ResFinder, VFDB, MLST, PAst, Phastest and CRISPR/Cas. SNP-based phylogenetic analysis with global OXA-48-like-harbouring CRPA genomes was carried out by CSI Phylogeny and iTOL for visualization.
Results
The clinical MDR strain of CRPA AMRIR00655 belonged to a novel sequence type ST5217 and serotype O11. Phenotypic tests followed by WGS revealed the presence of dual carbapenemases, OXA-181 (serine-carbapenemase) and VIM-2 (zinc-carbapenemase), both located on chromosome. blaOXA-181 resides between chromosomal genes encoding RodZ and PAP2 in P. aeruginosa, confirming chromosomal integration.4,261 bp of blaOXA-181-bearing contig-DNA showed 100% homology to K. pneumoniae plasmid pKP3-A. ISEcp1 was present on upstream and on downstream, △lysR, △ereA and repA genes were detected. blaVIM-2 was located within class 1 integron along with aacC6-II, dfrB5, aac(3)-Id, tniC in surrounding regions and 13,242 bp showing 100% identity to P. aeruginosa chromosome. Presence of other ARGs (blaPAO, blaOXA-488,aph(3′')-Ib, aph(6)-Id, crpP, catB7, fosA, sul2) and efflux-pump genes might explain its MDR phenotype. Virulence factors including T3SS (PscF, PopB, PopD, PcrV) and its effectors (ExoT, ExoU, ExoY) indicated the pathogenic potential of ST5217. Core genome analysis showed that ST5217 was closest with other high-risk clones ST1339 and ST773-harbouring blaOXA-48-like.
Conclusions
To the best of our knowledge, this is the first report of blaOXA-181-harbouring novel high-risk clone of CRPA ST5217/ExoU+/O11 in India which emphasises the spread of OXA-181 among bacteria other than Enterobacteriaceae-family and warrant close monitoring.
{"title":"Genomic analysis of a novel high-risk ST5217/ExoU+/O11 clone of carbapenem-resistant OXA-181- and VIM-2-producing Pseudomonas aeruginosa in India","authors":"Subhasree Roy , Souvik Nandy , Daichi Morita , Ranjan Kumar Nandy , Balaji Veeraraghavan , Kamini Walia , Santasabuj Das , Sulagna Basu","doi":"10.1016/j.jgar.2025.12.002","DOIUrl":"10.1016/j.jgar.2025.12.002","url":null,"abstract":"<div><h3>Objectives</h3><div>Studies of carbapenem-resistant <em>Pseudomonas aeruginosa</em> (CRPA)-harbouring OXA-48-like carbapenemases are rare. The study aimed to report the emergence and characterization of a novel high-risk clone of CRPA-harbouring OXA-48-like from India.</div></div><div><h3>Methods</h3><div>Identification, AST, phenotypic detection of carbapenemases and WGS using Ion-Torrent-S5 platform were carried out. Analyses included ResFinder, VFDB, MLST, PAst, Phastest and CRISPR/Cas. SNP-based phylogenetic analysis with global OXA-48-like-harbouring CRPA genomes was carried out by CSI Phylogeny and iTOL for visualization.</div></div><div><h3>Results</h3><div>The clinical MDR strain of CRPA AMRIR00655 belonged to a novel sequence type ST5217 and serotype O11. Phenotypic tests followed by WGS revealed the presence of dual carbapenemases, OXA-181 (serine-carbapenemase) and VIM-2 (zinc-carbapenemase), both located on chromosome. <em>bla</em><sub>OXA-181</sub> resides between chromosomal genes encoding RodZ and PAP2 in <em>P. aeruginosa</em>, confirming chromosomal integration<em>.</em>4,261 bp of <em>bla</em><sub>OXA-181</sub>-bearing contig-DNA showed 100% homology to <em>K. pneumoniae</em> plasmid pKP3-A. IS<em>Ecp1</em> was present on upstream and on downstream, △<em>lysR,</em> △<em>ereA</em> and <em>repA</em> genes were detected. <em>bla</em><sub>VIM-2</sub> was located within class 1 integron along with <em>aacC6-II, dfrB5, aac(3)-Id, tniC</em> in surrounding regions and 13,242 bp showing 100% identity to <em>P. aeruginosa</em> chromosome. Presence of other ARGs (<em>bla</em><sub>PAO</sub>, <em>bla</em><sub>OXA-488,</sub> <em>aph(3′')-Ib, aph(6)-Id, crpP, catB7, fosA, sul2</em>) and efflux-pump genes might explain its MDR phenotype. Virulence factors including T3SS (PscF, PopB, PopD, PcrV) and its effectors (ExoT, ExoU, ExoY) indicated the pathogenic potential of ST5217. Core genome analysis showed that ST5217 was closest with other high-risk clones ST1339 and ST773-harbouring <em>bla</em><sub>OXA-48-like</sub>.</div></div><div><h3>Conclusions</h3><div>To the best of our knowledge, this is the first report of <em>bla</em><sub>OXA-181</sub>-harbouring novel high-risk clone of CRPA ST5217/ExoU+/O11 in India which emphasises the spread of OXA-181 among bacteria other than Enterobacteriaceae-family and warrant close monitoring.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 158-161"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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