About this Research Topic

Background

The rising prevalence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) pathogens represents one of the most significant challenges in modern medicine. Invasive infections caused by MDR and XDR pathogens are estimated to cause over 2.8 million infections and 35,000 deaths annually in the United States alone. Globally, the mortality rate for some invasive infections exceeds 50%. The economic burden is also staggering, with drug-resistant infections costing the U.S. healthcare system more than $4.6 billion annually. Antibiotics, which are critical to modern medicine, play an essential role in treating bacterial infections such as pneumonia, sepsis, tuberculosis, and urinary tract infections, as well as preventing infections in surgical procedures and during cancer chemotherapy. Without effective antibiotics, these treatments and surgeries would become significantly more dangerous, leading to increased morbidity, mortality, and healthcare costs. The growing resistance of pathogens to most or all existing antimicrobial agents underscores the urgent need for innovative solutions to prevent a potential “post-antibiotic era” where even routine infections could become untreatable.

Currently, treatment and prophylaxis pipelines primarily rely on existing drug classes and their derivatives. This dependence has resulted in a limited arsenal of effective therapeutic options, posing a significant challenge in clinical practice. This issue is particularly critical for infections caused by fungal pathogens, mycobacteria, and Gram-positive and Gram-negative bacteria. Consequently, the emergence of MDR, XDR, PDR (pan-drug resistant), and TDR pathogens severely limits treatment options for infections caused by these organisms.

Historically, most antimicrobial compounds have been derived from mesophilic soil microorganisms. However, this source has been largely exhausted, highlighting the need for innovative strategies to identify new active compounds. Promising new molecules include those targeting:

1. Membrane biosynthesis pathways

2. Cell wall biosynthesis pathways

3. Transport machinery

Identifying novel targets within pathogens’ cells remains crucial, as it could expand the development of structurally and functionally innovative compounds. Additionally, antivirulence therapeutics offer a promising approach. These include:

- Antitoxins

- Quorum-sensing disruptors

- Virulence regulatory system silencers

- Agents that inhibit bacterial adherence and biofilm formation

In the meantime, combination therapies using currently available drugs have shown promise. This approach can help overcome resistance mechanisms while minimizing the emergence of further drug-resistant subpopulations.

Research Focus

This Research Topic aims to explore emerging antimicrobials against drug-resistant pathogens. We invite contributions that address the following aspects:

- Sources of new antimicrobial agents

- Mechanisms of action

- Spectrum of activity

- Combination antimicrobial therapies

- Mechanisms of resistance

We encourage the submission of high-quality original research, reviews, mini-reviews, and perspective articles that focus on, but are not limited to, the following themes:

1. **Novel compounds targeting **Mycobacterium tuberculosis

2. Innovative agents and combination therapies against:

- Drug-resistant Enterobacterales and non-fermenting bacteria

- Drug-resistant Staphylococcus spp. and Enterococcus spp.

3. Antifungals targeting MDR pathogens, including:

- Candida auris

- Trichophyton mentagrophytes/interdigitale Complex

- Emergomyces spp.

- Mucormycosis and other challenging fungal infections

4. Investigation of novel antimicrobial targets, focusing on microorganism-antimicrobial interactions at both phenotypic and molecular levels

5. Combination therapies with synergistic potential

6. Molecular mechanisms of resistance to emerging antimicrobials

7. Characterization of mobile genetic elements (MGEs) involved in the spread of resistance factors

8. Bacterial regulatory mechanisms contributing to adaptive resistance against novel antimicrobials

9. Molecular epidemiology of pathogens resistant to new treatments

This Research Topic seeks to advance our understanding of innovative antimicrobial solutions and their potential applications in combating drug-resistant infections.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: multidrug-resistance, pandrug-resitance, acquired resistance mechanism, Candida auris, Trichophyton mentagropytes, Trichophyton interdigitale, Emergomyces sp, Mucormycosis, total-drug resistance, novel antimicrobials

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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