Antibiotics for emerging pathogens - PubMed (original) (raw)
Review
Antibiotics for emerging pathogens
Michael A Fischbach et al. Science. 2009.
Abstract
Antibiotic-resistant strains of pathogenic bacteria are increasingly prevalent in hospitals and the community. New antibiotics are needed to combat these bacterial pathogens, but progress in developing them has been slow. Historically, most antibiotics have come from a small set of molecular scaffolds whose functional lifetimes have been extended by generations of synthetic tailoring. The emergence of multidrug resistance among the latest generation of pathogens suggests that the discovery of new scaffolds should be a priority. Promising approaches to scaffold discovery are emerging; they include mining underexplored microbial niches for natural products, designing screens that avoid rediscovering old scaffolds, and repurposing libraries of synthetic molecules for use as antibiotics.
Figures
Fig. 1
Multidrug-resistant strains of these bacterial pathogens are on the rise.
Fig. 2
Synthetic tailoring is widely used to create successive generations of antibiotic classes. Scaffolds are colored black; peripheral chemical modifications are colored red. The quinolone scaffold is synthetic, while the other scaffolds are natural products.
Fig. 3
Between 1962 and 2000, no major classes of antibiotics were introduced.
Fig. 4
The chemical structures of new and underexplored antibiotic scaffolds mentioned throughout the text are organized by type into three categories: synthetic, semisynthetic, and natural product. For synthetic and semisynthetic scaffolds, core scaffolds are shown in black and variable positions are shown in red.
Fig. 5
Similar articles
- [Emergence pathogens infections in ENT Department of Children's hospital in 2005-2008].
Zielnik-Jurkiewicz B, Rakowska-Szkudlarek M. Zielnik-Jurkiewicz B, et al. Otolaryngol Pol. 2009 Nov-Dec;63(6):513-9. doi: 10.1016/S0030-6657(09)70171-4. Otolaryngol Pol. 2009. PMID: 20198987 Polish. - [Analysis of the pathogenic characteristics of 162 severely burned patients with bloodstream infection].
Gong YL, Yang ZC, Yin SP, Liu MX, Zhang C, Luo XQ, Peng YZ. Gong YL, et al. Zhonghua Shao Shang Za Zhi. 2016 Sep 20;32(9):529-35. doi: 10.3760/cma.j.issn.1009-2587.2016.09.004. Zhonghua Shao Shang Za Zhi. 2016. PMID: 27647068 Chinese. - Advances in antibacterial therapy against emerging bacterial pathogens.
Pournaras S, Iosifidis E, Roilides E. Pournaras S, et al. Semin Hematol. 2009 Jul;46(3):198-211. doi: 10.1053/j.seminhematol.2009.03.007. Semin Hematol. 2009. PMID: 19549574 Review. - Staphylococcal Bacterial Persister Cells, Biofilms, and Intracellular Infection Are Disrupted by JD1, a Membrane-Damaging Small Molecule.
Dombach JL, Quintana JLJ, Detweiler CS. Dombach JL, et al. mBio. 2021 Oct 26;12(5):e0180121. doi: 10.1128/mBio.01801-21. Epub 2021 Oct 12. mBio. 2021. PMID: 34634935 Free PMC article. - The antibiotic resistance crisis, with a focus on the United States.
Martens E, Demain AL. Martens E, et al. J Antibiot (Tokyo). 2017 May;70(5):520-526. doi: 10.1038/ja.2017.30. Epub 2017 Mar 1. J Antibiot (Tokyo). 2017. PMID: 28246379 Review.
Cited by
- Development of antibiotic activity profile screening for the classification and discovery of natural product antibiotics.
Wong WR, Oliver AG, Linington RG. Wong WR, et al. Chem Biol. 2012 Nov 21;19(11):1483-95. doi: 10.1016/j.chembiol.2012.09.014. Chem Biol. 2012. PMID: 23177202 Free PMC article. - Rediscovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in Mycobacterium tuberculosis.
Wang H, Xu M, Engelhart CA, Zhang X, Yan B, Pan M, Xu Y, Fan S, Liu R, Xu L, Hua L, Schnappinger D, Chen S. Wang H, et al. J Biol Chem. 2021 Jan-Jun;296:100257. doi: 10.1016/j.jbc.2021.100257. Epub 2021 Jan 8. J Biol Chem. 2021. PMID: 33837735 Free PMC article. - Differential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages.
Chang D, Feng J, Liu H, Liu W, Sharma L, Dela Cruz CS. Chang D, et al. Innate Immun. 2020 Oct;26(7):618-626. doi: 10.1177/1753425920942582. Epub 2020 Aug 6. Innate Immun. 2020. PMID: 32762278 Free PMC article. - Endless Resistance. Endless Antibiotics?
Fisher JF, Mobashery S. Fisher JF, et al. Medchemcomm. 2016 Jan 1;7(1):37-49. doi: 10.1039/C5MD00394F. Epub 2015 Nov 3. Medchemcomm. 2016. PMID: 27746889 Free PMC article. - Novel apidaecin 1b analogs with superior serum stabilities for treatment of infections by gram-negative pathogens.
Berthold N, Czihal P, Fritsche S, Sauer U, Schiffer G, Knappe D, Alber G, Hoffmann R. Berthold N, et al. Antimicrob Agents Chemother. 2013 Jan;57(1):402-9. doi: 10.1128/AAC.01923-12. Epub 2012 Oct 31. Antimicrob Agents Chemother. 2013. PMID: 23114765 Free PMC article.
References
- Walsh C. Antibiotics: Actions, Origins, Resistance. ASM Press; Washington, DC: 2003.
- Nathan C, Goldberg FM. Nature reviews. 2005 Nov;4:887. - PubMed
- Nathan C. Nature. 2004 Oct 21;431:899. - PubMed
- von Nussbaum F, Brands M, Hinzen B, Weigand S, Habich D. Angewandte Chemie (International ed) 2006 Aug 4;45:5072. - PubMed
- Klevens RM, et al. Jama. 2007 Oct 17;298:1763. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- R01 GM049338/GM/NIGMS NIH HHS/United States
- GM49338/GM/NIGMS NIH HHS/United States
- GM20011/GM/NIGMS NIH HHS/United States
- R01 GM049338-17/GM/NIGMS NIH HHS/United States
- R01 GM020011-38/GM/NIGMS NIH HHS/United States
- R01 AI042738/AI/NIAID NIH HHS/United States
- R01 GM020011-39/GM/NIGMS NIH HHS/United States
- R01 AI042738-12/AI/NIAID NIH HHS/United States
- R01 GM020011/GM/NIGMS NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical