Navigating collateral sensitivity: insights into the mechanisms and applications of antibiotic resistance trade-offs.

The swift rise of antibiotic resistance, coupled with limited new antibiotic discovery, presents a significant hurdle to global public health, demanding innovative therapeutic solutions. Recently, collateral sensitivity (CS), the phenomenon in which resistance to one antibiotic increases vulnerability to another, has come to light as a potential path forward in this attempt. Targeting either unidirectional or reciprocal CS holds promise for constraining the emergence of drug resistance and notably enhancing treatment outcomes.

Malonate is relevant to the lung environment and induces genome-wide stress responses in Pseudomonas aeruginosa.

Versatility in carbon source utilization is a major contributor to niche adaptation in . Malonate is among the abundant carbon sources in the lung airways, yet it is understudied. Recently, we characterized how malonate impacts quorum sensing regulation, antibiotic resistance, and virulence factor production in .

Rescue of pyrimidine-defective through metabolic complementation.

Unlabelled: Chronic infections harbor multiple pathogens where dynamic interactions between members of the polymicrobial community play a major role in determining the infection outcome. For example, in a nutrient-rich polymicrobial infection, bacteria have the potential to undergo evolutionary changes that impair their ability to synthesize essential metabolites. This adaptation may facilitate metabolic interdependencies between neighboring pathogens and lead to difficult-to-treat chronic infections.

Global stress response in upon malonate utilization.

Unlabelled: Versatility in carbon source utilization assists in its adaptation to various niches. Recently, we characterized the role of malonate, an understudied carbon source, in quorum sensing regulation, antibiotic resistance, and virulence factor production in . These results indicate that global responses to malonate metabolism remain to be uncovered.

Development of a Polymicrobial Checkerboard Assay as a Tool for Determining Combinatorial Antibiotic Effectiveness in Polymicrobial Communities.

The checkerboard assay is a well-established tool used to determine the antimicrobial effects of two compounds in combination. Usually, data collected from the checkerboard assay use visible turbidity and optical density as a readout. While helpful in traditional checkerboard assays, these measurements become less useful in a polymicrobial context as they do not enable assessment of the drug effects on the individual members of the community.

Increased Susceptibility of to Ethionamide by Expressing PPs-Induced Rv0560c.

Tuberculosis, an infectious disease, is one of the leading causes of death worldwide. Drug-resistant tuberculosis exacerbates its threat. Despite long-term and costly treatment with second-line drugs, treatment failure rates and mortality remain high.

A novel class of antimicrobial drugs selectively targets a Mycobacterium tuberculosis PE-PGRS protein.

The continued spread of drug-resistant tuberculosis is one of the most pressing and complex challenges facing tuberculosis management worldwide. Therefore, developing a new class of drugs is necessary and urgently needed to cope with the increasing threat of drug-resistant tuberculosis. This study aims to discover a potential new class of tuberculosis drug candidates different from existing tuberculosis drugs.

Autoxidation of a C2-Olefinated Dihydroartemisinic Acid Analogue to Form an Aromatic Ring: Application to Serrulatene Biosynthesis.

Dihydroartemisinic acid (DHAA) is a plant natural product that undergoes a spontaneous endoperoxide-forming cascade reaction to yield artemisinin in the presence of air. The endoperoxide functional group gives artemisinin its biological activity that kills , the parasite that causes malaria. To enhance our understanding of the mechanism of this cascade reaction, 2,3-didehydrodihydroartemisinic acid (2,3-didehydro-DHAA), a DHAA derivative with a double bond at the C2-position, was synthesized.

Biodegradation and Removal of PAHs by Isolated from Fermented Food.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment. They are highly toxigenic and carcinogenic. Probiotic bacteria isolated from fermented foods were tested to check their ability to degrade and/or detoxify PAHs.

Interspecies Metabolic Complementation in Cystic Fibrosis Pathogens via Purine Exchange.

Cystic fibrosis (CF) is a genetic disease frequently associated with chronic lung infections caused by a consortium of pathogens. It is common for auxotrophy (the inability to biosynthesize certain essential metabolites) to develop in clinical isolates of the dominant CF pathogen , indicating that the CF lung environment is replete in various nutrients. Many of these nutrients are likely to come from the host tissues, but some may come from the surrounding polymicrobial community within the lungs of CF patients as well.

The Impact of Intraspecies and Interspecies Bacterial Interactions on Disease Outcome.

The human microbiota is an array of microorganisms known to interact with the host and other microbes. These interactions can be competitive, as microbes must adapt to host- and microorganism-related stressors, thus producing toxic molecules, or cooperative, whereby microbes survive by maintaining homeostasis with the host and host-associated microbial communities. As a result, these microbial interactions shape host health and can potentially result in disease.

Synthesis and activity of BNF15 against drug-resistant .

Tuberculosis is the leading cause of mortality among infectious diseases worldwide. Finding a new competent anti tubercular therapy is essential. We screened thousands of compounds and evaluated their efficacy against .

Melanin Bleaching and Melanogenesis Inhibition Effects of PMC48 Isolated from Korean Perilla Leaf Kimchi.

Overproduction and accumulation of melanin in the skin will darken the skin and cause skin disorders. So far, components that can inhibit tyrosinase, a melanin synthase of melanocytes, have been developed and used as ingredients of cosmetics or pharmaceutical products. However, most of existing substances can only inhibit the biosynthesis of melanin while melanin that is already synthesized and deposited is not directly decomposed.

In vitro activity of DNF-3 against drug-resistant Mycobacterium tuberculosis.

Due to the emergence of multidrug-resistant and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis, new antituberculosis drugs are urgently required to improve the efficacy of current tuberculosis (TB) treatment. To achieve this goal, ca. 1000 chemical compounds were screened for potential antimycobacterial activity, among which methyl 5-(2-diethylaminoethoxy)-7,12-dioxo-7,12 dihydrodinaphtho[1,2-b;2',3'-d]furan-6-carboxylate (DNF-3) showed strong activity against all of the tested drug-susceptible and -resistant M.

In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis.

Background: Tuberculosis is a very serious infectious disease that threatens humanity, and the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR) strains resistant to drugs suggests that new drug development is urgent. In order to develop new tuberculosis drug, we have conducted in vitro anti-tubercular tests on thousands of plant-derived substances and finally found collinin extracted from the leaves of Zanthoxylum schinifolium, which has an excellent anti-tuberculosis effect.

Purpose: To isolate an anti-tubercular bioactive compound from the leaves of Z.

In Vitro Effect of DFC-2 on Mycolic Acid Biosynthesis in .

DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate, is reported to have antitubercular effects against . At concentrations ranging from 0.19 to 0.

In vitro Antitubercular Activity of 3-Deoxysappanchalcone Isolated From the Heartwood of Caesalpinia sappan Linn.

Responsible for nearly 1.5 million deaths every year, the infectious disease tuberculosis remains one of the most serious challenges to global health. The emergence of multidrug-resistant tuberculosis and, more recently, extensively drug-resistant tuberculosis poses a significant threat in our effort to control this epidemic.

In vitro activity of alpha-viniferin isolated from the roots of Carex humilis against Mycobacterium tuberculosis.

This study explores the antitubercular activity of α-viniferin, a bioactive phytochemical compound obtained from Carex humilis. α-Viniferin was active against both drug-susceptible and -resistant strains of Mycobacterium tuberculosis at MICs of 4.6 μM in culture broth medium and MICs of 2.

Thymoquinone (TQ) inhibits the replication of intracellular Mycobacterium tuberculosis in macrophages and modulates nitric oxide production.

Background: Human tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent.