Siderophore conjugates to combat antibiotic-resistant bacteria

被引:47
作者
Rayner, Beth [1 ,2 ]
Verderosa, Anthony D. [1 ,2 ]
Ferro, Vito [2 ,3 ]
Blaskovich, Mark A. T. [1 ,2 ,3 ]
机构
[1] Univ Queensland, Inst Mol Biosci, Ctr Superbug Solut, Brisbane, Qld, Australia
[2] Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld, Australia
[3] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
CATECHOL-SUBSTITUTED CEPHALOSPORIN; SELECTIVE SIDEROMYCIN ANTIBIOTICS; TONB-DEPENDENT TRANSPORTERS; BETA-LACTAM ANTIBIOTICS; GRAM-NEGATIVE BACTERIA; IN-VITRO ANTIBACTERIAL; PSEUDOMONAS-AERUGINOSA; IRON TRANSPORT; MEDIATED UPTAKE; DIAMINO ACIDS;
D O I
10.1039/d2md00465h
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antimicrobial resistance (AMR) is a global threat to society due to the increasing emergence of multi-drug resistant bacteria that are not susceptible to our last line of defence antibiotics. Exacerbating this issue is a severe gap in antibiotic development, with no new clinically relevant classes of antibiotics developed in the last two decades. The combination of the rapidly increasing emergence of resistance and scarcity of new antibiotics in the clinical pipeline means there is an urgent need for new efficacious treatment strategies. One promising solution, known as the 'Trojan horse' approach, hijacks the iron transport system of bacteria to deliver antibiotics directly into cells - effectively tricking bacteria into killing themselves. This transport system uses natively produced siderophores, which are small molecules with a high affinity for iron. By linking antibiotics to siderophores, to make siderophore antibiotic conjugates, the activity of existing antibiotics can potentially be reinvigorated. The success of this strategy was recently exemplified with the clinical release of cefiderocol, a cephalosporin-siderophore conjugate with potent antibacterial activity against carbapenem-resistant and multi-drug resistant Gram-negative bacilli. This review discusses the recent advancements in siderophore antibiotic conjugates and the challenges associated with the design of these compounds that need to be overcome to deliver more efficacious therapeutics. Potential strategies have also been suggested for new generations of siderophore-antibiotics with enhanced activity.
引用
收藏
页码:800 / 822
页数:24
相关论文
共 126 条
[1]   The Alternative Role of Enterobactin as an Oxidative Stress Protector Allows Escherichia coli Colony Development [J].
Adler, Conrado ;
Corbalan, Natalia S. ;
Peralta, Daiana R. ;
Fernanda Pomares, Maria ;
de Cristobal, Ricardo E. ;
Vincent, Paula A. .
PLOS ONE, 2014, 9 (01)
[2]   Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides [J].
Allred, Benjamin E. ;
Rupert, Peter B. ;
Gauny, Stacey S. ;
An, Dahlia D. ;
Ralston, Corie Y. ;
Sturzbecher-Hoehne, Manuel ;
Strong, Roland K. ;
Abergel, Rebecca J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (33) :10342-10347
[3]   Cefiderocol (S-649266), A new siderophore cephalosporin exhibiting potent activities against Pseudomonas aeruginosa and other gram-negative pathogens including multi-drug resistant bacteria: Structure activity relationship [J].
Aoki, Toshiaki ;
Yoshizawa, Hidenori ;
Yamawaki, Kenji ;
Yokoo, Katsuki ;
Sato, Jun ;
Hisakawa, Shinya ;
Hasegawa, Yasushi ;
Kusano, Hiroki ;
Sano, Masayuki ;
Sugimoto, Hideki ;
Nishitani, Yasuhiro ;
Sato, Takafumi ;
Tsuji, Masakatsu ;
Nakamura, Rio ;
Nishikawa, Toru ;
Yamano, Yoshinori .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 155 :847-868
[4]   Mucosal Lipocalin 2 Has Pro-Inflammatory and Iron-Sequestering Effects in Response to Bacterial Enterobactin [J].
Bachman, Michael A. ;
Miller, Virginia L. ;
Weiser, Jeffrey N. .
PLOS PATHOGENS, 2009, 5 (10)
[5]   Iron and Pseudomonas aeruginosa biofilm formation [J].
Banin, E ;
Vasil, ML ;
Greenberg, EP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (31) :11076-11081
[6]   Chelator-induced dispersal and killing of Pseudomonas aeruginosa cells in a biofilm [J].
Banin, E ;
Brady, KM ;
Greenberg, EP .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2006, 72 (03) :2064-2069
[7]   The potential of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent [J].
Banin, Ehud ;
Lozinski, Alina ;
Brady, Keith M. ;
Berenshtein, Eduard ;
Butterfield, Phillip W. ;
Moshe, Maya ;
Chevion, Mordechai ;
Greenberg, Everett Peter ;
Banin, Eyal .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (43) :16761-16766
[8]   Cleavable linkers in antibody-drug conjugates [J].
Bargh, Jonathan D. ;
Isidro-Llobet, Albert ;
Parker, Jeremy S. ;
Spring, David R. .
CHEMICAL SOCIETY REVIEWS, 2019, 48 (16) :4361-4374
[9]   Siderophores: More than Stealing Iron [J].
Behnsen, Judith ;
Raffatellu, Manuela .
MBIO, 2016, 7 (06)
[10]   CONSTITUTION OF THE DEFERRIFORM OF THE ALBOMYCINS DELTA-1, DELTA-2, AND EPSILON [J].
BENZ, G ;
SCHRODER, T ;
KURZ, J ;
WUNSCHE, C ;
KARL, W ;
STEFFENS, G ;
PFITZNER, J ;
SCHMIDT, D .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1982, 21 (07) :527-528