| 1. |
- Jensen, Jorgen S., et al.
(författare)
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Antimicrobial treatment and resistance in sexually transmitted bacterial infections
- 2024
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Ingår i: Nature Reviews Microbiology. - : Nature Publishing Group. - 1740-1526 .- 1740-1534. ; 22:7, s. 435-450
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Forskningsöversikt (refereegranskat)abstract
- Sexually transmitted infections (STIs) have been part of human life since ancient times, and their symptoms affect quality of life, and sequelae are common. Socioeconomic and behavioural trends affect the prevalence of STIs, but the discovery of antimicrobials gave hope for treatment, control of the spread of infection and lower rates of sequelae. This has to some extent been achieved, but increasing antimicrobial resistance and increasing transmission in high-risk sexual networks threaten this progress. For Neisseria gonorrhoeae, the only remaining first-line treatment (with ceftriaxone) is at risk of becoming ineffective, and for Mycoplasma genitalium, for which fewer alternative antimicrobial classes are available, incurable infections have already been reported. For Chlamydia trachomatis, in vitro resistance to first-line tetracyclines and macrolides has never been confirmed despite decades of treatment of this highly prevalent STI. Similarly, Treponema pallidum, the cause of syphilis, has remained susceptible to first-line penicillin.
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| 2. |
- Krautkramer, Kimberly A., et al.
(författare)
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Gut microbial metabolites as multi-kingdom intermediates
- 2021
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Ingår i: Nature Reviews Microbiology. - : Springer Science and Business Media LLC. - 1740-1526 .- 1740-1534. ; 19, s. 77-94
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota contributes to host physiology through the production of a myriad of metabolites. In this Review, Backhed and colleagues discuss the major classes of microbial metabolites, highlight examples of how microbial metabolites affect host health and provide a potential framework for integration of discovery-based metabolite studies with mechanistic work. The gut microbiota contributes to host physiology through the production of a myriad of metabolites. These metabolites exert their effects within the host as signalling molecules and substrates for metabolic reactions. Although the study of host-microbiota interactions remains challenging due to the high degree of crosstalk both within and between kingdoms, metabolite-focused research has identified multiple actionable microbial targets that are relevant for host health. Metabolites, as the functional output of combined host and microorganism interactions, provide a snapshot in time of an extraordinarily complex multi-organism system. Although substantial work remains towards understanding host-microbiota interactions and the underlying mechanisms, we review the current state of knowledge for each of the major classes of microbial metabolites with emphasis on clinical and translational research implications. We provide an overview of methodologies available for measurement of microbial metabolites, and in addition to discussion of key challenges, we provide a potential framework for integration of discovery-based metabolite studies with mechanistic work. Finally, we highlight examples in the literature where this approach has led to substantial progress in understanding host-microbiota interactions.
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| 3. |
- Larsson, D. G. Joakim, 1969, et al.
(författare)
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Antibiotic resistance in the environment
- 2022
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Ingår i: Nature Reviews Microbiology. - : Springer Science and Business Media LLC. - 1740-1526 .- 1740-1534. ; 20, s. 257-269
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance is a global health challenge, involving the transfer of bacteria and genes between humans, animals and the environment. Although multiple barriers restrict the flow of both bacteria and genes, pathogens recurrently acquire new resistance factors from other species, thereby reducing our ability to prevent and treat bacterial infections. Evolutionary events that lead to the emergence of new resistance factors in pathogens are rare and challenging to predict, but may be associated with vast ramifications. Transmission events of already widespread resistant strains are, on the other hand, common, quantifiable and more predictable, but the consequences of each event are limited. Quantifying the pathways and identifying the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance are key components to understand and manage the resistance crisis as a whole. In this Review, we present our current understanding of the roles of the environment, including antibiotic pollution, in resistance evolution, in transmission and as a mere reflection of the regional antibiotic resistance situation in the clinic. We provide a perspective on current evidence, describe risk scenarios, discuss methods for surveillance and the assessment of potential drivers, and finally identify some actions to mitigate risks. In this Review, Larsson and Flach discuss the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance, and they explore environmental surveillance strategies that could complement clinical surveillance systems.
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| 4. |
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| 5. |
- Roemhild, Roderich, et al.
(författare)
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The physiology and genetics of bacterial responses to antibiotic combinations
- 2022
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Ingår i: Nature Reviews Microbiology. - : Springer Nature. - 1740-1526 .- 1740-1534. ; 20:8, s. 478-490
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Forskningsöversikt (refereegranskat)abstract
- Combining several antibiotics, either in mixtures or sequential order, is proposed to increase treatment efficacy and reduce resistance evolution. In this Review, Andersson and colleagues discuss the effects of antibiotic combinations, the directional effects of previous antibiotic treatments and the role of stress-response systems as well as the interactions between drugs and resistance mutations. Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy.
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| 6. |
- Theuretzbacher, Ursula, et al.
(författare)
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The global preclinical antibacterial pipeline
- 2020
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Ingår i: Nature Reviews Microbiology. - : Springer Science and Business Media LLC. - 1740-1526 .- 1740-1534. ; 18:5, s. 275-285
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Forskningsöversikt (refereegranskat)abstract
- With rising rates of antibiotic resistance, it is essential that new antibiotics are developed. In this Review, Theuretzbacher et al. take stock of the preclinical antibiotic pipeline and discuss challenges and opportunities for the discovery and development of novel antibacterial therapies. Antibacterial resistance is a great concern and requires global action. A critical question is whether enough new antibacterial drugs are being discovered and developed. A review of the clinical antibacterial drug pipeline was recently published, but comprehensive information about the global preclinical pipeline is unavailable. This Review focuses on discovery and preclinical development projects and has found, as of 1 May 2019, 407 antibacterial projects from 314 institutions. The focus is on Gram-negative pathogens, particularly bacteria on the WHO priority bacteria list. The preclinical pipeline is characterized by high levels of diversity and interesting scientific concepts, with 135 projects on direct-acting small molecules that represent new classes, new targets or new mechanisms of action. There is also a strong trend towards non-traditional approaches, including diverse antivirulence approaches, microbiome-modifying strategies, and engineered phages and probiotics. The high number of pathogen-specific and adjunctive approaches is unprecedented in antibiotic history. Translational hurdles are not adequately addressed yet, especially development pathways to show clinical impact of non-traditional approaches. The innovative potential of the preclinical pipeline compared with the clinical pipeline is encouraging but fragile. Much more work, focus and funding are needed for the novel approaches to result in effective antibacterial therapies to sustainably combat antibacterial resistance.
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| 7. |
- Wilson, Daniel N., et al.
(författare)
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Target protection as a key antibiotic resistance mechanism
- 2020
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Ingår i: Nature Reviews Microbiology. - : Nature Publishing Group. - 1740-1526 .- 1740-1534. ; 18:11, s. 637-648
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Forskningsöversikt (refereegranskat)abstract
- Antibiotic resistance is mediated through several distinct mechanisms, most of which are relatively well understood and the clinical importance of which has long been recognized. Until very recently, neither of these statements was readily applicable to the class of resistance mechanism known as target protection, a phenomenon whereby a resistance protein physically associates with an antibiotic target to rescue it from antibiotic-mediated inhibition. In this Review, we summarize recent progress in understanding the nature and importance of target protection. In particular, we describe the molecular basis of the known target protection systems, emphasizing that target protection does not involve a single, uniform mechanism but is instead brought about in several mechanistically distinct ways.
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