Options to combat bacterial infections are becoming scarce. We require innovative approaches to enhance the discovery of effective antimicrobials capable of combating bacteria resistant to multiple or all antibiotics. These methods should either directly eliminate resistant bacteria or indirectly influence their viability by inhibiting their virulence or reducing their resistance to antibiotics. One interesting approach is to analyze ancient remedies used to treat bacterial infections, formulate them, and test them against modern microbes. This field has recently been named "ancientbiotics." This approach allows us to leverage centuries of empirical knowledge accumulated, from traditional medicines across various ancient cultures worldwide. The strategy has already yielded promising formulations to combat the ESKAPE group of nosocomial pathogens. Additionally, molecular de-extinction, which involves genome analysis of extinct species to search for useful antimicrobials, such as peptides, offers another avenue. In this review, we compile the antimicrobial effects of ancient remedies and de-extinct molecules known to modern science and discuss possible new strategies to further harness the potential of past remedies and molecules to fight the rise of superbugs.

Antimicrobial resistance (AMR) poses a critical global health threat, leading to approximately 1.27 million deaths annually from infectious diseases resistant to existing antibiotics. Factors such as antibiotic misuse and environmental contamination have accelerated AMR, with the COVID-19 pandemic exacerbating the issue due to increased antibiotic usage. However, the development of new antibiotics has stagnated, with only a few approved in recent years, and many facing resistance. Among the priority pathogens identified by the WHO, Pseudomonas aeruginosa stands out as a significant concern due to its multidrug resistance and virulence. P. aeruginosa infections are challenging to treat due to intrinsic and acquired resistance mechanisms, as well as its ability to form biofilms. Additionally, P. aeruginosa produces a plethora of virulence factors, including proteases, siderophores, and toxins, further complicating treatment. Quorum sensing (QS) systems play a crucial role in regulating bacterial physiology and virulence factor expression. P. aeruginosa employs three QS systems, making it an attractive target for quorum quenching (QQ) strategies. Enzymes such as AHL lactonases, acylases, and oxidoreductases have shown promise in inhibiting QS, thus reducing virulence without impacting bacterial growth. Furthermore, natural QS inhibitors produced by various organisms offer potential therapeutic alternatives. Despite promising results in vitro, translating QQ strategies to clinical settings remains challenging. Nevertheless, QQ represents a novel approach in combating multidrug-resistant infections and warrants further investigation as a complementary therapeutic strategy alongside traditional antibiotics. This review summarizes enzymes with Qurorum Quenching activity evaluated against the pathogen P. aeruginosa and their potential applications in combination therapies.

After a time away from the classrooms and laboratories due to the global pandemic, the return to the teaching activities during the semester represented a challenge to both teachers and students. Our particular situation in a Microbial Physiology course was the necessity of imparting in a shorter time, laboratory practices that usually take longer. This article describes a two-week long laboratory exercise that covers several concepts in an interrelated way: conjugation as a gene transfer mechanism, regulation of microbial physiology, production of secondary metabolites, degradation of macromolecules and biofilm formation. Utilizing a Quorum Quenching (QQ) strategy, the Quorum Sensing (QS) system of Pseudomonas aeruginosa is first attenuated. Then, phenotypes regulated by QS are evidenced. QS is a regulatory mechanism of the microbial physiology that relays on signal molecules. QS is related in P. aeruginosa to several virulence factors, some of which are exploited in the laboratory practices presented in this work. QQ is phenomenon by which QS is interrupted or attenuated. We utilized a QQ approach based on the enzymatic degradation of the P. aeruginosa QS signals in order to put in evidence QS-regulated traits that are relevant for our Microbial Physiology course.