About this Research Topic
The rampant spread of antibiotic resistance, which constitutes one of the major global public health threats of our time, has drawn increased attention to the urgent need for new and improved antimicrobial therapies. The cellular envelope of bacteria constitutes the primary line of defense against environmental stress since it is responsible for sensing, as well as triggering the activation of the appropriate stress response pathways. The remarkable mechanisms of bacterial adaptation to adverse environmental conditions are indeed inherent to antimicrobial resistance and tolerance, which involve a significant and tightly controlled cellular reorganization at the transcriptomic, proteomic and metabolic level. Remodeling of the cellular envelope upon stress exposure, including changes in the membrane lipid composition, plays a central role in both maintenance of envelope integrity and stress adaptation. A better understanding on the crosstalk between membrane lipid metabolism and bacterial cell envelope homeostasis leads to novel pathways for antibacterial development.
One quarter of currently prescribed antimicrobials are directed against proteins involved in bacterial envelope homeostasis, including β-lactam antibiotics and “last resort” drugs like vancomycin or daptomycin, making the cellular envelope an attractive target for improving antibiotic efficacy. Despite the emergence of widespread clinical resistance, few new therapies targeting the bacterial cell envelope have been developed over the past two decades. The importance of bacterial membrane phospholipids in the development of resistance and tolerance to antibiotics has become increasingly evident, yet the precise role played by membrane lipids in stress adaptation remains elusive. Alterations in the content of major phospholipids lead to global cellular effects, such as impairments of cellular envelope structure and function, perturbations of cellular physiology leading to impaired adaptability and phospholipid-dependent susceptibility to environmental stress. A deeper understanding of the regulatory mechanisms between membrane lipid homeostasis and cellular functions will open new avenues for the use of lipid metabolism as a target for antibacterial therapies development and improvement.
A detailed mechanistic understanding of how essential processes are connected to contribute to cell envelope formation, stability and drug tolerance leads to novel insights to combat antimicrobial resistance. The scope of this Research Topic is to cover promising, recent, and novel research trends in bacterial cellular envelope homeostasis. It pays particular attention to bacterial cellular envelope remodeling upon exposure to antibiotics, both from a protein and lipid point of view. This collection of articles aims to contribute to new understandings of how membrane lipids regulate bacterial physiology. Areas to be covered in this Research Topic may include, but are not limited to:
• Regulation of phospholipid biogenesis/Regulation of fatty acid biogenesis under stress conditions/Alteration of lipid metabolism associated with antimicrobial resistance
• Membrane assembly (transport of phospholipids/LPS)
• Interaction between cell wall and cell membrane metabolism. Functional interplay between cell wall and lipids
• Role of host lipids on bacterial physiology and antibiotic resistance. Utilization of host lipids by bacterial pathogens
• Small molecule modifiers of lipid metabolism in bacterial pathogens
• Biophysical, physiological, and functional consequences of altered lipid metabolism
Keywords: Bacteria, Membrane, Lipid, Cellular envelope, Antimicrobial resistance, Metabolism
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