Comparative genome analysis reveals high-level drug resistance markers in a clinical isolate of subsp MF GZ001.

Md Shah Alam, Ping Guan, Yuting Zhu, Sanshan Zeng, Xiange Fang, Shuai Wang, Buhari Yusuf, Jingran Zhang, Xirong Tian, Cuiting Fang, Yamin Gao, Mst Sumaia Khatun, Zhiyong Liu, H M Adnan Hameed, Yaoju Tan, Jinxing Hu, Jianxiong Liu, Tianyu Zhang
Author Information
  1. Md Shah Alam: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  2. Ping Guan: State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, China.
  3. Yuting Zhu: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  4. Sanshan Zeng: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  5. Xiange Fang: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  6. Shuai Wang: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  7. Buhari Yusuf: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  8. Jingran Zhang: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  9. Xirong Tian: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  10. Cuiting Fang: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  11. Yamin Gao: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  12. Mst Sumaia Khatun: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  13. Zhiyong Liu: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  14. H M Adnan Hameed: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  15. Yaoju Tan: State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, China.
  16. Jinxing Hu: State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, China.
  17. Jianxiong Liu: State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, China.
  18. Tianyu Zhang: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Abstract

Introduction: Infections caused by non-tuberculosis mycobacteria are significantly worsening across the globe. M. fortuitum complex is a rapidly growing pathogenic species that is of clinical relevance to both humans and animals. This pathogen has the potential to create adverse effects on human healthcare.
Methods: The MF GZ001 clinical strain was collected from the sputum of a 45-year-old male patient with a pulmonary infection. The morphological studies, comparative genomic analysis, and drug resistance profiles along with variants detection were performed in this study. In addition, comparative analysis of virulence genes led us to understand the pathogenicity of this organism.
Results: Bacterial growth kinetics and morphology confirmed that MF GZ001 is a rapidly growing species with a rough morphotype. The MF GZ001 contains 6413573 bp genome size with 66.18 % high G+C content. MF GZ001 possesses a larger genome than other related mycobacteria and included 6156 protein-coding genes. Molecular phylogenetic tree, collinearity, and comparative genomic analysis suggested that MF GZ001 is a novel member of the M. fortuitum complex. We carried out the drug resistance profile analysis and found single nucleotide polymorphism (SNP) mutations in key drug resistance genes such as rpoB, katG, AAC(2')-Ib, gyrA, gyrB, embB, pncA, blaF, thyA, embC, embR, and iniA. In addition, the MF GZ001strain contains mutations in iniA, iniC, pncA, and ribD which conferred resistance to isoniazid, ethambutol, pyrazinamide, and para-aminosalicylic acid respectively, which are not frequently observed in rapidly growing mycobacteria. A wide variety of predicted putative potential virulence genes were found in MF GZ001, most of which are shared with well-recognized mycobacterial species with high pathogenic profiles such as M. tuberculosis and M. abscessus.
Discussion: Our identified novel features of a pathogenic member of the M. fortuitum complex will provide the foundation for further investigation of mycobacterial pathogenicity and effective treatment.

Keywords

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MeSH Term

Animals
Humans
Middle Aged
Microbial Sensitivity Tests
Phylogeny
Drug Resistance, Bacterial
Mycobacteriaceae

Word Cloud

Created with Highcharts 10.0.0MFGZ001analysisresistanceMdrugfortuitumcomparativegenesmycobacteriacomplexrapidlygrowingpathogenicspeciesclinicalgenomicgenomepotentialprofilesadditionvirulencepathogenicitymorphologycontainshighnovelmemberfoundmutationspncAiniAmycobacterialIntroduction:Infectionscausednon-tuberculosissignificantlyworseningacrossgloberelevancehumansanimalspathogencreateadverseeffectshumanhealthcareMethods:straincollectedsputum45-year-oldmalepatientpulmonaryinfectionmorphologicalstudiesalongvariantsdetectionperformedstudyledusunderstandorganismResults:Bacterialgrowthkineticsconfirmedroughmorphotype6413573bpsize6618%G+Ccontentpossesseslargerrelatedincluded6156protein-codingMolecularphylogenetictreecollinearitysuggestedcarriedprofilesinglenucleotidepolymorphismSNPkeyrpoBkatGAAC2'-IbgyrAgyrBembBblaFthyAembCembRGZ001straininiCribDconferredisoniazidethambutolpyrazinamidepara-aminosalicylicacidrespectivelyfrequentlyobservedwidevarietypredictedputativesharedwell-recognizedtuberculosisabscessusDiscussion:identifiedfeatureswillprovidefoundationinvestigationeffectivetreatmentComparativerevealshigh-levelmarkersisolatesubspMycobacteriumpathogenesis

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