Subtractive Genomics Approach for Identification of Novel Therapeutic Drug Targets in Mycoplasma genitalium

被引:16
作者
Fatoba, Abiodun Joseph [1 ]
Okpeku, Moses [1 ]
Adeleke, Matthew Adekunle [1 ]
机构
[1] Univ KwaZulu Natal, Sch Life Sci, Discipline Genet, P Bag X54001, ZA-4000 Durban, South Africa
来源
PATHOGENS | 2021年 / 10卷 / 08期
关键词
Mycoplasma genitalium; drug targets; metabolic pathways; pathogen; proteins; subtractive genomics; 2016 EUROPEAN GUIDELINE; METABOLIC PATHWAYS; 2-COMPONENT; INFECTION; BIOSYNTHESIS; URETHRITIS; SECRETION; GENES;
D O I
10.3390/pathogens10080921
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Mycoplasma genitalium infection is a sexually transmitted infection that causes urethritis, cervicitis, and pelvic inflammatory disease (PID) in men and women. The global rise in antimicrobial resistance against recommended antibiotics for the treatment of M. genitalium infection has triggered the need to explore novel drug targets against this pathogen. The application of a bioinformatics approach through subtractive genomics has proven highly instrumental in predicting novel therapeutic targets against a pathogen. This study aimed to identify essential and non-homologous proteins with unique metabolic pathways in the pathogen that could serve as novel drug targets. Based on this, a manual comparison of the metabolic pathways of M. genitalium and the human host was done, generating nine pathogen-specific metabolic pathways. Additionally, the analysis of the whole proteome of M. genitalium using different bioinformatics databases generated 21 essential, non-homologous, and cytoplasmic proteins involved in nine pathogen-specific metabolic pathways. The further screening of these 21 cytoplasmic proteins in the DrugBank database generated 13 druggable proteins, which showed similarity with FDA-approved and experimental small-molecule drugs. A total of seven proteins that are involved in seven different pathogen-specific metabolic pathways were finally selected as novel putative drug targets after further analysis. Therefore, these proposed drug targets could aid in the design of potent drugs that may inhibit the functionality of these pathogen-specific metabolic pathways and, as such, lead to the eradication of this pathogen.
引用
收藏
页数:12
相关论文
共 77 条
  • [51] KAAS: an automatic genome annotation and pathway reconstruction server
    Moriya, Yuki
    Itoh, Masumi
    Okuda, Shujiro
    Yoshizawa, Akiyasu C.
    Kanehisa, Minoru
    [J]. NUCLEIC ACIDS RESEARCH, 2007, 35 : W182 - W185
  • [52] Morya V.D., 2010, Journal of Computer Science and Systems Biology, V3, P62, DOI [DOI 10.4172/JCSB.1000058, 10.4172/jcsb.1000058]
  • [53] The regulatory protein PhoP controls susceptibility to the host inflammatory response in Shigella flexneri
    Moss, JE
    Fisher, PE
    Vick, B
    Groisman, EA
    Zychlinsky, A
    [J]. CELLULAR MICROBIOLOGY, 2000, 2 (06) : 443 - 452
  • [54] Macrolide and fluoroquinolone resistance-associated mutations in Mycoplasma genitalium in Johannesburg, South Africa, 2007-2014
    Muller, Etienne E.
    Mahlangu, Mahlape P.
    Lewis, David A.
    Kularatne, Ranmini S.
    [J]. BMC INFECTIOUS DISEASES, 2019, 19 (1)
  • [55] Increasing Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium
    Murray, Gerald L.
    Bradshaw, Catriona S.
    Bissessor, Melanie
    Danielewski, Jennifer
    Garland, Suzanne M.
    Jensen, Jorgen S.
    Fairley, Christopher K.
    Tabrizi, Sepehr N.
    [J]. EMERGING INFECTIOUS DISEASES, 2017, 23 (05) : 809 - 812
  • [56] Regulation of the pspA virulence factor and essential pcsB murein biosynthetic genes by the phosphorylated VicR (YycF) response regulator in Streptococcus pneumoniae
    Ng, WL
    Tsui, HCT
    Winkler, ME
    [J]. JOURNAL OF BACTERIOLOGY, 2005, 187 (21) : 7444 - 7459
  • [57] Novel antibiotic screening methods to awaken silent or cryptic secondary metabolic pathways in actinomycetes
    Onaka, Hiroyasu
    [J]. JOURNAL OF ANTIBIOTICS, 2017, 70 (08) : 865 - 870
  • [58] Target validation - Determining druggabiity
    Owens, Joanna
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (03) : 187 - 187
  • [59] Recent advances in the biosynthesis of penicillins, cephalosporins and clavams and its regulation
    Ozcengiz, Gulay
    Demain, Arnold L.
    [J]. BIOTECHNOLOGY ADVANCES, 2013, 31 (02) : 287 - 311
  • [60] Production of microbial secondary metabolites: Regulation by the carbon source
    Ruiz, Beatriz
    Chavez, Adan
    Forero, Angela
    Garcia-Huante, Yolanda
    Romero, Alba
    Sanchez, Mauricio
    Rocha, Diana
    Sanchez, Brenda
    Rodriguez-Sanoja, Romina
    Sanchez, Sergio
    Langley, Elizabeth
    [J]. CRITICAL REVIEWS IN MICROBIOLOGY, 2010, 36 (02) : 146 - 167