Wenxiao Jiang , Guanning Huang , Shuya Pan , Xin Chen , Ting Liu , Ziyi Yang , Tianfeng Chen , Xueqiong Zhu
{"title":"TRAIL-driven targeting and reversing cervical cancer radioresistance by seleno-nanotherapeutics through regulating cell metabolism","authors":"Wenxiao Jiang , Guanning Huang , Shuya Pan , Xin Chen , Ting Liu , Ziyi Yang , Tianfeng Chen , Xueqiong Zhu","doi":"10.1016/j.drup.2023.101033","DOIUrl":"10.1016/j.drup.2023.101033","url":null,"abstract":"<div><p><span>Recently, radioresistance<span> has become a major obstacle in the radiotherapy of cervical cancer<span>. To demonstrate enhanced radiosensitization against radioresistant cervical cancer, radioresistant cervical cancer cell line was developed and the mechanism of radioresistance was explored. Due to the overexpression of (death receptor 5, DR5) in cervical cancer, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-overexpressed cervical cancer cell membrane-camouflaged Cu</span></span></span><sub>2−x</sub><span>Se nanomedicine (CCMT) was designed. Since the CCMT was encapsulated with TRAIL-modified cell membrane, it represented high target to cervical cancer cell and immune evasion. Furthermore, Cu</span><sub>2−x</sub><span>Se had the ability to scavenge glutathione (GSH) and produce ·OH with excess H</span><sub>2</sub>O<sub>2</sub><span> in the tumor microenvironment. The presence of CCMT combined with radiation therapy could effectively increase the </span><sup>1</sup>O<sub>2</sub> produced by X-rays. <em>In vitro</em> and <em>in vivo</em><span> studies elaborated that CCMT exhibited excellent radiosensitization properties to reverse radiotolerance by scavenging GSH and promoting DNA damage, apoptosis<span>, mitochondrial membrane potential damage and metabolic disruption. Collectively, this study suggested that the development of TRAIL-overexpressed cell membrane-camouflaged Cu</span></span><sub>2−x</sub>Se nanomedicine could advance future cervical cancer treatment and minimize the disadvantages associated with radiation treatment.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138562429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vaccine effects on COVID-19 infection with bivalent boosting by age group","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.drup.2023.101039","DOIUrl":"10.1016/j.drup.2023.101039","url":null,"abstract":"<div><p>This paper examines time-series vaccine effectiveness on COVID-19 infection with/without a bivalent booster dose by 6 age groups such as 18–29, 30–49, 50–64, 65–79, 80+, and all_ages respectively. CDC’s COVID data on rates of COVID-19 cases and deaths by updated (bivalent) booster status was used in this study. This result concludes that there is no difference between vaccines with or without a bivalent booster dose for preventing COVID-19 infection in 6 age groups 18–29, 30–49, 50–64, 65–79, 80+, and all_ages. Vaccination is effective in two age groups of 65-79 and 80+ for preventing COVID-19 infection. However, vaccine effectiveness against COVID-19 infection has not been confirmed in the 18–29 and 30–49 age groups.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139041561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chao Liu , Juan Yi , Ming Lu , Ping Yang , Chunjing Du , Fan Jiang , Pengcheng Du , Ning Shen
{"title":"Dynamic within-host cefiderocol heteroresistance caused by blaSHV-12 amplification in pandrug-resistant and hypervirulent Klebsiella pneumoniae sequence type 11","authors":"Chao Liu , Juan Yi , Ming Lu , Ping Yang , Chunjing Du , Fan Jiang , Pengcheng Du , Ning Shen","doi":"10.1016/j.drup.2023.101038","DOIUrl":"10.1016/j.drup.2023.101038","url":null,"abstract":"<div><h3>Aims</h3><p><span>Although cefiderocol (FDC) is not prescribed in China, FDC-resistant pandrug-resistant hypervirulent </span><span><em>Klebsiella pneumoniae</em></span> (PDR-hvKp) is emerging. In this study, we performed FDC susceptibility testing of clinical Kp isolates to explore the prevalence of FDC-resistant isolates and the mechanism of FDC-resistance.</p></div><div><h3>Methods</h3><p>We retrospectively selected 151 carbapenem-resistant Kp isolates to assess FDC susceptibility. Seven isolates harboring <em>bla</em><sub>SHV-12</sub><span> from two patients were enrolled for whole-genome sequencing. The antimicrobial resistance, virulence, </span><em>bla</em><sub>SHV-12</sub> expression, and fitness costs in different media were examined. The amplification of <em>bla</em><sub>SHV-12</sub> was further investigated by qPCR and long-read sequencing.</p></div><div><h3>Results</h3><p><span>The 151 isolates showed a low MIC</span><sub>50</sub>/MIC<sub>90</sub> (1/4 mg/L) of FDC. The seven isolates were ST11 PDR-hvKp, and two represented FDC-resistance (MIC=32 mg/L). The IncR/IncFII plasmids of two FDC-resistant isolates harbored 6 and 15 copies of <em>bla</em><sub>SHV-12</sub>, whereas four FDC-susceptible isolates carried one copy and one harbored three copies. These <em>bla</em><sub>SHV-12</sub> genes concatenated together and were located within the same 7.3 kb fragment flanked by IS26, which contributed to the increased expression and FDC resistance without fitness costs. The amplification of <em>bla</em><sub>SHV-12</sub> and FDC resistance could be induced by FDC in vitro and reversed during continuous passage.</p></div><div><h3>Conclusions</h3><p>The amplification of <em>bla</em><sub>SHV-12</sub><span><span> and the consequent dynamic within-host heteroresistance are important concerns for the rational application of antibiotics. Long-read sequencing might be a superior way to detect resistance </span>gene amplification rapidly and accurately.</span></p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139041622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Yan , Dan Liu , Jingmei Wang , Weiming You , Wenguang Yang , Siqi Yan , Wangxiao He
{"title":"Rewiring chaperone-mediated autophagy in cancer by a prion-like chemical inducer of proximity to counteract adaptive immune resistance","authors":"Jin Yan , Dan Liu , Jingmei Wang , Weiming You , Wenguang Yang , Siqi Yan , Wangxiao He","doi":"10.1016/j.drup.2023.101037","DOIUrl":"10.1016/j.drup.2023.101037","url":null,"abstract":"<div><p>Chaperone-mediated autophagy (CMA), a proteolytic system contributing to the degradation of intracellular proteins in lysosomes, is upregulated in tumors for pro-tumorigenic and pro-survival purposes. In this study, bioinformatics analysis revealed the co-occurrence of upregulated CMA and PD-L1 accumulation in metastatic melanoma with adaptive immune resistance (AIR) to anti-PD1 treatment, suggesting the potential therapeutic effects of rewiring CMA for PD-L1 degradation. Furthermore, this co-occurrence is attributed to IFN-γ-mediated compensatory up-regulation of PD-L1 and CMA, accompanied by enhanced macropinocytosis. Drawing inspiration from the cellular uptake of prions via macropinocytosis, a prion-like chemical inducer of proximity called SAP was engineered using self-assembly of the designed chiral peptide PHA. By exploiting sensitized macropinocytosis, SAP clandestinely infiltrates tumor cells and subsequently disintegrates into PHA, which reprograms CMA by inducing PD-L1 close to HSPA8. SAP degrades PD-L1 in a CMA-dependent manner and effectively restores the anti-tumor immune response in both allografting and Hu-PDX melanoma mouse models with AIR while upholding a high safety profile. Collectively, the reported SAP not only presents an immune reactivation strategy with clinical translational potential for overcoming AIR in cutaneous melanomas but serves as a reproducible example of precision-medicine-guided drug development that fully leverages specific cellular indications in pathological states.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764623001206/pdfft?md5=42137547ed8c3b961713c68b891a1c1c&pid=1-s2.0-S1368764623001206-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139034636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keyi Yu , Zhenzhou Huang , Yue Xiao , He Gao , Xuemei Bai , Duochun Wang
{"title":"Global spread characteristics of CTX-M-type extended-spectrum β-lactamases: A genomic epidemiology analysis","authors":"Keyi Yu , Zhenzhou Huang , Yue Xiao , He Gao , Xuemei Bai , Duochun Wang","doi":"10.1016/j.drup.2023.101036","DOIUrl":"10.1016/j.drup.2023.101036","url":null,"abstract":"<div><h3>Background</h3><p>Extended-spectrum β-lactamases (ESBLs) producing bacteria have spread worldwide and become a global public health concern. Plasmid-mediated transfer of ESBLs is an important route for resistance acquisition.</p></div><div><h3>Methods</h3><p>We collected 1345 complete sequences of plasmids containing CTX-Ms from public database. The global transmission pattern of plasmids and evolutionary dynamics of CTX-Ms have been inferred. We applied the pan-genome clustering based on plasmid genomes and evolution analysis to demonstrate the transmission events.</p></div><div><h3>Findings</h3><p>Totally, 48 CTX-Ms genotypes and 186 incompatible types of plasmids were identified. The geographical distribution of CTX-Ms showed significant differences across countries and continents. CTX-M-14 and CTX-M-55 were found to be the dominant genotypes in Asia, while CTX-M-1 played a leading role in Europe. The plasmids can be divided into 12 lineages, some of which forming distinct geographical clusters in Asia and Europe, while others forming hybrid populations. The Inc types of plasmids are lineage-specific, with the CTX-M-1_IncI1-I (Alpha) and CTX-M-65_IncFII (pHN7A8)/R being the dominant patterns of cross-host and cross-regional transmission. The IncI-I (Alpha) plasmids with the highest number, were presumed to form communication groups in Europe-Asia and Asia-America-Oceania, showing the transmission model as global dissemination and regional microevolution. Meanwhile, the main kinetic elements of <em>bla</em><sub>CTX-Ms</sub> showed genotypic preferences. IS<em>Ecpl</em> and IS<em>26</em> were most frequently involved in the transfer of CTX-M-14 and CTX-M-65, respectively. IS<em>15</em> has become a crucial participant in mediating the dissemination of <em>bla</em><sub>CTX-Ms</sub>. Interestingly, <em>bla</em><sub>TEM</sub> and <em>bla</em><sub>CTX-Ms</sub> often coexisted in the same transposable unit. Furthermore, antibiotic resistance genes associated with aminoglycosides, sulfonamides and cephalosporins showed a relatively high frequency of synergistic effects with CTX-Ms.</p></div><div><h3>Conclusions</h3><p>We recognized the dominant <em>bla</em><sub>CTX-Ms</sub> and mainstream plasmids of different continents. The results of this study provide support for a more effective response to the risks associated with the evolution of <em>bla</em><sub>CTX-Ms</sub>-bearing plasmids, and lay the foundation for genotype-specific epidemiological surveillance of resistance, which are of important public health implications.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S136876462300119X/pdfft?md5=a37339fb1d5cc73447ba11bd61364003&pid=1-s2.0-S136876462300119X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138887046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cefiderocol: Clinical application and emergence of resistance","authors":"Liang Wang , Jie Zhu , Liang Chen , Hong Du","doi":"10.1016/j.drup.2023.101034","DOIUrl":"10.1016/j.drup.2023.101034","url":null,"abstract":"<div><p>Antibacterial drug<span><span> resistance of gram-negative bacteria (GNB) results in high morbidity and mortality of GNB infection, seriously threaten human health globally. Developing new antibiotics has become the critical need for dealing with drug-resistant bacterial infections. </span>Cefiderocol<span><span> is an iron carrier cephalosporin<span><span> that achieves drug accumulation through a unique “Trojan horse” strategy into the bacterial periplasm. It shows high </span>antibacterial activity against multidrug-resistant (MDR) </span></span>Enterobacteriaceae<span> and MDR non-fermentative bacteria. The application of cefiderocol offers new hope for treating clinical drug-resistant bacterial infections. However, limited clinical data and uncertainties about its resistance mechanisms constrain the choice of its therapeutic use. This review aimed to summarize the clinical applications, drug resistance mechanisms, and co-administration of cefiderocol.</span></span></span></p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joanna R. Thomas, William J.E. Frye, Robert W. Robey, Michael M. Gottesman
{"title":"Progress in characterizing ABC multidrug transporters in zebrafish","authors":"Joanna R. Thomas, William J.E. Frye, Robert W. Robey, Michael M. Gottesman","doi":"10.1016/j.drup.2023.101035","DOIUrl":"10.1016/j.drup.2023.101035","url":null,"abstract":"<div><p><span><span>Zebrafish have proved to be invaluable for modeling complex physiological processes<span><span> shared by all vertebrate animals. Resistance of cancers and other diseases to drug treatment can occur owing to expression of the ATP-dependent multidrug transporters ABCB1, </span>ABCG2<span>, and ABCC1, either because of expression of these transporters by the target cells to reduce intracellular concentrations of </span></span></span>cytotoxic drugs<span><span> at barrier sites such as the blood-brain barrier (BBB) to limit penetration of drugs into privileged compartments, or by affecting the absorption, distribution, and excretion of drugs administered orally, through the skin, or directly into the bloodstream. We describe the drug specificity, </span>cellular localization, and function of zebrafish orthologs of </span></span>multidrug resistance<span><span> ABC transporters with the goal of developing zebrafish models to explore the physiological and pathophysiological functions of these transporters. Finally, we provide context demonstrating the utility of zebrafish in studying cancer drug resistance. Our ultimate goal is to improve </span>treatment of cancer and other diseases which are affected by ABC multidrug resistance transporters.</span></p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138679521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xu Lin , Qingyi Zhang , Qi Li , Jun Deng , Shuying Shen , Muhu Tang , Xianghua Ye , Cong Ji , Yuhong Yang , Yuxiao Chen , Liping Zeng , Jiangang Zhao , M.B.N. Kouwenhoven , Don Eliseo Lucero-Prisno III , Junjie Huang , Yangling Li , Bo Zhang , Jian Hu
{"title":"Upregulation of CoQ shifts ferroptosis dependence from GPX4 to FSP1 in acquired radioresistance","authors":"Xu Lin , Qingyi Zhang , Qi Li , Jun Deng , Shuying Shen , Muhu Tang , Xianghua Ye , Cong Ji , Yuhong Yang , Yuxiao Chen , Liping Zeng , Jiangang Zhao , M.B.N. Kouwenhoven , Don Eliseo Lucero-Prisno III , Junjie Huang , Yangling Li , Bo Zhang , Jian Hu","doi":"10.1016/j.drup.2023.101032","DOIUrl":"10.1016/j.drup.2023.101032","url":null,"abstract":"<div><p>Acquired radioresistance is the primary contributor to treatment failure of radiotherapy, with ferroptosis is identified as a significant mechanism underlying cell death during radiotherapy. Although resistance to ferroptosis has been observed in both clinical samples of radioresistant cells and cell models, its mechanism remains unidentified. Herein, our investigation revealed that radioresistant cells exhibited greater tolerance to Glutathione Peroxidase 4 (GPX4) inhibitors and, conversely, increased sensitivity to ferroptosis suppressor protein 1 (FSP1) inhibitors compared to their sensitive counterparts. This observation suggested that FSP1 might play a dominant role in the development of radioresistance. Notably, the knockout of FSP1 demonstrated considerably superior efficacy in resensitizing cells to radiotherapy compared to the knockout of GPX4. To elucidate the driving force behind this functional shift, we conducted a metabolomic assay, which revealed an upregulation of Coenzyme Q (CoQ) synthesis and a downregulation of glutathione synthesis in the acquired radioresistance cells. Mechanistically, CoQ synthesis was found to be supported by aarF domain containing kinase 3-mediated phosphorylation of CoQ synthases, while the downregulation of Solute carrier family 7 member 11 led to decreased glutathione synthesis. Remarkably, our retrospective analysis of clinical response data further validated that the additional administration of statin during radiotherapy, which could impede CoQ production, effectively resensitized radioresistant cells to radiation. In summary, our findings demonstrate a dependency shift from GPX4 to FSP1 driven by altered metabolite synthesis during the acquisition of radioresistance. Moreover, we provide a promising therapeutic strategy for reversing radioresistance by inhibiting the FSP1-CoQ pathway.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764623001152/pdfft?md5=e217dcb3a41316b0cdbe650ffa4eb31d&pid=1-s2.0-S1368764623001152-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138564883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Li , Xinran Sun , Ning Dong , Zhiqiang Wang , Ruichao Li
{"title":"Global distribution and genomic characteristics of carbapenemase-producing Escherichia coli among humans, 2005–2023","authors":"Yan Li , Xinran Sun , Ning Dong , Zhiqiang Wang , Ruichao Li","doi":"10.1016/j.drup.2023.101031","DOIUrl":"10.1016/j.drup.2023.101031","url":null,"abstract":"<div><p>Carbapenem-resistant <em>Escherichia coli</em><span><span> (CREC) has become a major public health problem worldwide. To date, there is a limited understanding of the global distribution of CREC. In this study, we performed a comprehensive genomic analysis of 7, 731 CRECs of human origin collected from different countries worldwide between 2005 and 2023. Our results showed that these CRECs were distributed in 75 countries, mainly from the United States (17.49%), China (14.88%), and the United Kingdom (14.73%). Eight </span>carbapenemases<span> were identified among the CRECs analyzed, including KPC, IMP, NDM, VIM, OXA, FRI, GES, and IMI. NDM was the most predominant carbapenemase (52.15%), followed by OXA (30.09%) and KPC (14.72%). Notably, all CRECs carried multiple antibiotic resistance genes (ARGs), with 178 isolates carrying </span></span><em>mcr-1</em> and 9 isolates carrying <em>tet</em><span>(X). The CREC isolates were classified into 465 known sequence types (STs), with ST167 being the most common (11.5%). Correlation analysis demonstrated the significant role of mobile genetic elements<span> in facilitating the transfer of carbapenem resistance genes. Furthermore, some CRECs from different countries showed high genetic similarity, suggesting clonal transmission exists. According to the GWAS results, the genetic difference of </span></span><em>bla</em><sub>NDM</sub><span>-positive CRECs from China were mainly enriched in bacterial Type IV secretion system pathways compared with those from the United Kingdom and the United States. Therefore, continuous global surveillance of CRECs is imperative in the future.</span></p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenwen Liu , Yawen Yu , Yuting Wang , Ting Yang , Yingying Kong , Xinyou Xie , Jun Zhang
{"title":"Deciphering the genetic basis of resistome and virulome diversity among multidrug-resistant Mycoplasma hominis","authors":"Wenwen Liu , Yawen Yu , Yuting Wang , Ting Yang , Yingying Kong , Xinyou Xie , Jun Zhang","doi":"10.1016/j.drup.2023.101029","DOIUrl":"10.1016/j.drup.2023.101029","url":null,"abstract":"<div><p><span><em>Mycoplasma hominis</em></span><span>, a commensal bacterium that commonly inhabits the genital tract, leading to infections in both the genitourinary and extragenital regions. However, the antimicrobial resistance and pathogenic mechanisms of </span><em>M. hominis</em> isolated from extra-urogenital cystic abscess is largely unknown. This study reports the genomic epidemiological characteristics of a <em>M. hominis</em><span> isolate recovered from a pelvic abscess<span><span> sample in China. Genomic DNA was extracted and sequenced using Illumina HiSeq X Ten platform. De novo assembly was performed and </span>in silico<span> analysis was accomplished by multiple bioinformatics tools. For phylogenomic analysis, publicly available </span></span></span><em>M. hominis</em><span><span> genomes were retrieved from NCBI GenBank database. Whole genome sequencing data showed that the </span>genome size of </span><em>M. hominis</em> MH4246 was calculated as 679,746 bp, with 558 protein-coding sequences and a G + C content of 26.9%. <em>M. hominis</em><span><span><span> MH4246 is resistant to fluoroquinolones and </span>macrolides<span>, harboring mutations in the quinolone resistance-determining regions (QRDRs) (GyrA S153L, ParC S91I and ParE V417I) and </span></span>23S rRNA gene (G280A, C1500T, T1548C and T2218C). Multiple virulence determinants, such as </span><em>tuf</em>, <em>hlyA</em>, <em>vaa</em>, <em>oppA</em>, <em>MHO_0730</em> and <em>alr</em><span> genes, were identified. Phylogenetic analysis showed that the closest relative of </span><em>M. hominis</em><span><span> MH4246 was the strain MH-1 recovered from China, which differed by 3490 SNPs. Overall, this study contributes to the comprehension of genomic characteristics, antimicrobial resistance patterns, and the mechanisms underlying the </span>pathogenicity<span> of this pathogen.</span></span></p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}