Metabolic Pathways and Metabolites as Potential Targets to Combat Antibiotic Microbial Resistance

Dear Colleagues,

The emergence of antimicrobial resistance (AMR) in bacteria is a major concern in current medicine, as it poses a serious global risk to public health. As a result, new strategies are needed to combat AMR in bacteria. The emergence of new resistant strains and limited antibiotics treatment available have made it increasingly difficult to treat infections effectively. For example, only two antibiotics for tuberculosis have been approved in the last 20 years, and new clinical cases of new antibiotics-resistant tuberculosis are reported occasionally. A similar concern is seen with other bacteria, namely acinetobacter, staphylococcus, pseudomonas, etc. According to a report published by the U.S. National Strategy for Combating Antibiotic-Resistant Bacteria, approximately 2 million Americans are infected with antibiotics-resistant bacteria each year, and at least 23,000 of them die subsequently. Moreover, this situation of antibiotic resistance is much worse in other, developing countries. In recent years, metabolomics has been identified as a promising tool for understanding the mechanism of antibiotic resistance and identifying new drug targets. Studies have shown that the metabolic condition of bacteria during antibiotic treatment contributes to or results from AMR. This makes it crucial to understand that metabolic processes that drive AMR can be used to regulate metabolic activity during treatment. The critical cellular changes associated with AMR resistance are energy production, cell wall modifications, and cellular interactions. Targeting cellular energy production mainly involves targeting cellular aerobic respiration. However, several pathogens, including pseudomonas and mycobacteria, can utilize anaerobic respiration, namely the nitrate respiratory chain, to survive in an oxygen-depleted environment. Nevertheless, pathogens may be resensitized to aerobic respiration if supplemented with carbon metabolites, which enhance the TCA cycle to promote the synthesis of electron carriers and improve the efficacy of the drugs against resistant strains. Resistant strains can also change the cell envelope components, such as modification of LPS, that lead to AMR. For example, LPS structural modifications lead to the development of polymyxin antibiotics resistance in microbes. Another critical method of reducing antibiotic susceptibility that pathogens use is biofilm formation. Biofilm formation requires bacterial interaction between bacteria through quorum sensing systems. Therefore, targeting quorum sensing systems via the identification of metabolites needed for cellular interaction and biofilm formation is a promising approach. Metabolomics technologies have evolved significantly. These technologies allow the metabolite identification and quantification of biochemical networks. Targeted and untargeted metabolic profiling are two different metabolic methodologies used for broad metabolic coverage and enhanced structural resolution of identified molecules, respectively. Studies have analyzed that antibiotics-sensitive pathogens have different metabolic responses to various drugs than antibiotics-resistant pathogens. Metabolic methods have several advantages for investigating AMR. First, metabolomics can provide a broad view of metabolic changes in response to antibiotics treatment, allowing researchers to identify potential targets and mechanisms. Additionally, metabolic methods provide real-time information not captured by genomic or proteomic approaches. Metabolic approaches can also be used to capture host metabolites that can target host pathways or help diagnose infectious diseases. Metabolomics can provide key information on the metabolic alternations that take place in the host as result of the microbes. These metabolic alternations can be utilized to find metabolic signatures connected to certain diseases, which can be used to manage or diagnose infectious diseases. Many studies have proposed breath metabolites as an identification tool to detect disease. Thus, new metabolic pathways and metabolites can be targeted to combat AMR and target host metabolites for better disease management and diagnosis using cutting-edge metabolomics technologies and methods. However, more research is needed to fully realize metabolomics clinical potential in infectious diseases and other diseases. This Special Issue accepts submissions of original research articles, reviews, mini-reviews, and commentaries. The focus will be on, but not limited to, the following subtopics: advances in microbial metabolomics; futuristic non-antibiotic treatment targeting metabolism; identification of metabolic signatures and biomarkers for infectious disease; microbiota-derived metabolites and their role in infectious disease and AMR; role of metabolites in early diagnosis of infection; metabolic approaches to understand and control AMR; targeting host metabolism to develop sustainable therapies; microbial metabolic modeling and novel drug discoveries; metabolic biomarkers and drug repurposing to control AMR; and methods and technical developments in microbial metabolomics.

Dr. Vijay Soni
Dr. Aditya Sharma
Guest Editors

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• antibiotics
• antimicrobial resistance
• bacterial metabolism
• computational biology
• diagnosis
• futuristic non-antibiotics treatment
• metabolites
• metabolomics
• mycobacterium
• targeted metabolomics
• untargeted metabolomics
• metabolic modeling
• multi-omics
• biomarkers
• drug development
• infectious disease