Resistance to third-generation Tetracyclines

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Background

From the time of discovery of first natural tetracyclines in the 1940s,
these antibiotics have demonstrated utmost efficacy towards a wide range of bacterial pathogens and became one of the most widely used antibiotic classes. Their potency, however, was compromised by the following rapid increase in resistance to this class of antibiotics, mainly mediated by horizontal transfer of genes encoding ribosomal protection and drug efflux mechanisms. The second generation of semi-synthetic tetracyclines, which include doxycycline and minocycline, have been developed in the 1960s to circumvent the resistance to the first-generation tetracyclines. Although they retained, to some extent, efficacy against certain bacterial pathogens, a growing resistance problem once again compromised the possibility of their broad use in the treatment of serious infections. The first representative of the third-generation tetracylines, tigecycline, which is a glycylcycline antibiotic, was approved for clinical use in 2005. Currently, there are a number of other glycylcyclines and fluorocyclines under development or already approved for clinical use. The latter include eravacycline, omadacycline and sarecycline, which were approved in 2018. There are worrying signs, however, that the efficacy of the third-generation tetracyclines could be similarly compromised by a rising resistance problem. In particular, there are indications that the rapid dissemination of the tet(X) genes into the human bacterial pathogens may undermine their efficiency for clearing serious bacterial infections. Another recent important observation is that the use of “older” tetracyclines in food animals may be a driving force behind the dissemination of resistance to the newer third-generation tetracyclines.

In the past, close monitoring of processes leading to the rise and dissemination of resistance to recently introduced antibiotics have been limited and largely impossible because of the lack of corresponding technologies. Presently, however, we are presented with a unique opportunity to observe and understand these mechanisms. More importantly, this knowledge may help us to develop strategies to counteract the development of antibiotic resistance in bacterial pathogens. Thus, the main objective of this research topic is collecting contributions that help us to understand the mechanisms that lead to the rise and dissemination of resistance to the third-generation tetracyclines.

Particular contributions in the form of any acceptable format may include but not limited to:
1. Surveillance and epidemiology of resistance to third-generation tetracyclines.
2. One Health approach to the problem of resistance to third- generation tetracyclines.
3. Mechanisms of resistance to third-generation tetracyclines.
4. Efficiency of therapy by third-generation tetracyclines.
5. Development of novel third-generation tetracyclines.

Keywords: Third-generation tetracyclines, Fluorocyclines, Eravacycline, Omadacycline, Sarecycline, Animals, One Health., Tigecycline, Glycylcyclines, Resistance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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