Exploring the Mechanisms of Second Messenger Signaling in Mycobacteria: Novel Approaches to Address Antimicrobial Resistance, Biofilm, Persistence, and Drug- Resistance Challenges

In the field of infectious diseases, bacterial pathogens continue to pose a significant threat to global health. The ever-increasing concern of antimicrobial resistance (AMR) has underscored the urgent need for innovative solutions in combating infections. Among the outcomes of the COVID-19 pandemic, the World Health Organization (WHO) has emphasized the utmost importance of addressing critical priority infections, such as Mycobacterium tuberculosis (Mtb) and those caused by ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. These infections demand immediate attention due to their resistance and potential to spread, worsened by the pandemic's impact on antibiotic efficacy. To combat these challenges, it is essential to chart new courses of exploration for novel antibiotic development. Recent decades have unveiled the pivotal role of second messengers (c-di-GMP, (p)ppGpp, and c-di-AMP) as regulatory orchestrators of multicellular behaviors, including biofilm formation, virulence factors, and biofilm-mediated persistence across diverse bacterial species, including mycobacteria. Notably, these signaling molecules also profoundly influence virulence properties, triggering immunological responses and modulating bacterial persistence, quorum sensing, and chronic infections within the human host.

Here we propose an interdisciplinary Research Topic that aims to highlight the latest research exploring the world of second messenger signaling in mycobacteria, shedding light on potential avenues for tackling antibiotic resistance, disrupting biofilm formation, and curbing persistent infections. We invite articles that cover advances in understanding the molecular basis of antibiotic resistance mechanisms and their applications to discover novel routes for developing new antibiotics in reshaping the landscape of mycobacterial infection. We welcome Original Research, Reviews, Mini-Reviews, Methods, Hypothesis and Theory, Perspectives, and Opinion papers focusing on, but not limited to, the following subthemes:

• Molecular insights into antimicrobial resistance mechanisms: unraveling the intricate molecular mechanisms underlying antimicrobial resistance in mycobacteria, to understand novel targets for therapeutic intervention.

• Novel antibiotic discovery pathways: exploring unconventional routes for developing new antibiotics, harnessing insights from second messenger signaling to overcome AMR.

• Interrupting biofilm formation strategies: investigating strategies to disrupt and inhibit biofilm formation in mycobacteria, offering potential avenues for enhancing treatment efficacy.

• Strategies for controlling persistent infections: connecting second messenger signaling knowledge with innovative approaches to tackle persistent mycobacterial infections and reduce their impact on global health.

• Clinical applications of second messenger signaling: bridging the gap between research and practice by exploring how insights into second messenger signaling can translate into novel clinical approaches for managing mycobacterial infections.

• Host-pathogen interactions and immune responses: examining the intricate interplay between second messenger signaling, host immune responses, and mycobacterial infections to uncover potential therapeutic strategies.

• Next-generation therapeutics targeting second messengers: the importance of developing next-generation therapeutics that directly target second messenger signaling pathways, and their potential to combat mycobacterial infections.

• Technological advances in studying second messengers: novel methodologies and technologies that enable the comprehensive study of second messenger signaling, lashing advancements in mycobacterial infection research.

Keywords: ExploriSecond Messenger Signaling, Mycobacteria, Antimicrobial Resistance, Biofilm, Drug-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.