Siderophores; iron scavengers: the novel & promising targets for pathogen specific antifungal therapy

被引:13
作者
Balhara, Meenakshi [1 ]
Chaudhary, Renu [1 ]
Ruhil, Sonam [1 ]
Singh, Bharat [1 ]
Dahiya, Nisha [2 ]
Parmar, Virinder S. [3 ]
Jaiwal, Pawan. K. [1 ]
Chhillar, Anil K. [1 ]
机构
[1] Maharshi Dayanand Univ, Ctr Biotechnol, Rohtak, Haryana, India
[2] Indian Council Med Res, Div Epidemiol & Communicable Dis, Delhi, India
[3] Univ Delhi, Dept Chem, Bioorgan Lab, Delhi, India
关键词
Siderophore; virulence; homeostasis; opportunistic; trojan horse; NONRIBOSOMAL PEPTIDE SYNTHETASES; INVASIVE PULMONARY ASPERGILLOSIS; FLAVIN-DEPENDENT MONOOXYGENASES; OPPORTUNISTIC FUNGAL PATHOGEN; SMALL-MOLECULE INHIBITION; AMPHOTERICIN-B; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; MYCOBACTERIUM-TUBERCULOSIS; CRYPTOCOCCAL MENINGITIS;
D O I
10.1080/14728222.2016.1254196
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: The recent emergence of resistance, toxicity paradigm and limited efficacy of conventional antifungal drugs necessitate the identification of de novo targets in fungal metabolism. One of the most critical physiological processes during in vivo pathogenesis is maintenance of iron homeostasis. The most life threatening opportunistic human fungal pathogens like Aspergillus, Candida and Cryptococcus exploit the siderophore mediated iron uptake mechanism either for survival, virulence, propagation or resistance to oxidative stress envisaged in vivo during infection.Areas covered: In this review, we will highlight the metabolic pathways; specifically siderophore biosynthesis, uptake and utilisation, triggered in the fungal pathogens in iron starving conditions and the various putative targets viable in these pathways to be recruited as novel therapeutic antidotes either via biosynthetic enzymes catalytic site inhibitors or as drug conjugates through trojan horse approach and further role in the development of fungal specific reliable diagnostic markers.Expert opinion: Siderophores are the weapons released by a pathogen to conquer the battle for iron acquisition. Hence, the fungal siderophore biosynthetic pathways along with their uptake and utilisation mechanisms represent an ideal target for pathogen specific, host friendly therapeutic strategy which would block the proliferation of parasite without causing any harm to the mammalian host.
引用
收藏
页码:1477 / 1489
页数:13
相关论文
共 120 条
  • [31] Groll AH, 1998, ADV PHARMACOL, V44, P343, DOI 10.1016/S1054-3589(08)60129-5
  • [32] The interplay between vacuolar and siderophore-mediated iron storage in Aspergillus fumigatus
    Gsaller, Fabio
    Eisendle, Martin
    Lechner, Beatrix Elisabeth
    Schrettl, Markus
    Lindner, Herbert
    Mueller, Daniela
    Geley, Stephan
    Haas, Hubertus
    [J]. METALLOMICS, 2012, 4 (12) : 1262 - 1270
  • [33] Ciclopirox for the treatment of superficial fungal infections: a review
    Gupta, AK
    Skinner, AR
    [J]. INTERNATIONAL JOURNAL OF DERMATOLOGY, 2003, 42 : 3 - 9
  • [34] Characterization of the Aspergillus nidulans transporters for the siderophores enterobactin and triacetylfusarinine C
    Haas, H
    Schoeser, M
    Lesuisse, E
    Ernst, JF
    Parson, W
    Abt, B
    Winkelmann, G
    Oberegger, H
    [J]. BIOCHEMICAL JOURNAL, 2003, 371 (371) : 505 - 513
  • [35] Siderophores in fungal physiology and virulence
    Haas, Hubertus
    Eisendle, Martin
    Turgeon, B. Gillian
    [J]. ANNUAL REVIEW OF PHYTOPATHOLOGY, 2008, 46 : 149 - 187
  • [36] An Iron-Mimicking, Trojan Horse-Entering Fungi-Has the Time Come for Molecular Imaging of Fungal Infections?
    Haas, Hubertus
    Petrik, Milos
    Decristoforo, Clemens
    [J]. PLOS PATHOGENS, 2015, 11 (01) : 1 - 7
  • [37] Fungal siderophore metabolism with a focus on Aspergillus fumigatus
    Haas, Hubertus
    [J]. NATURAL PRODUCT REPORTS, 2014, 31 (10) : 1266 - 1276
  • [39] The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion
    Heymann, P
    Gerads, M
    Schaller, M
    Dromer, F
    Winkelmann, G
    Ernst, JF
    [J]. INFECTION AND IMMUNITY, 2002, 70 (09) : 5246 - 5255
  • [40] The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence
    Hissen, AHT
    Wan, ANC
    Warwas, ML
    Pinto, LJ
    Moore, MM
    [J]. INFECTION AND IMMUNITY, 2005, 73 (09) : 5493 - 5503