Phocaeicola vulgatus shapes the long-term growth dynamics and evolutionary adaptations of Clostridioides difficile.

Clostridioides difficile can transiently or persistently colonize the human gut, posing a risk for infections. This colonization is influenced by complex molecular and ecological interactions with the human gut microbiota. By investigating C.

Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes.

The human gut pathogen Clostridioides difficile displays substantial inter-strain genetic variability and confronts a changeable nutrient landscape in the gut. We examined how human gut microbiota inter-species interactions influence the growth and toxin production of various C. difficile strains across different nutrient environments.

Human gut microbiota interactions shape the long-term growth dynamics and evolutionary adaptations of .

can transiently or persistently colonize the human gut, posing a risk factor for infections. This colonization is influenced by complex molecular and ecological interactions with human gut microbiota. By investigating dynamics in human gut communities over hundreds of generations, we show patterns of stable coexistence, instability, or competitive exclusion.

Elucidating human gut microbiota interactions that robustly inhibit diverse strains across different nutrient landscapes.

The human gut pathogen displays extreme genetic variability and confronts a changeable nutrient landscape in the gut. We mapped gut microbiota inter-species interactions impacting the growth and toxin production of diverse strains in different nutrient environments. Although negative interactions impacting are prevalent in environments promoting resource competition, they are sparse in an environment containing -preferred carbohydrates.

Mechanistic Insight into the Inhibitory Activity of Elasnin-Based Coating against Early Marine Biofilms.

Marine biofilms are multispecies microbial communities on surfaces that are crucial to the marine environment. They cause marine corrosion, biofouling, and transmission of marine pathogens and thus pose a great threat to public health and the maritime industry. To control marine biofilms, effective and environmentally friendly antibiofilm compounds are highly needed.

Pterosin sesquiterpenoids from Pteris laeta Wall. ex Ettingsh. protect cells from glutamate excitotoxicity by modulating mitochondrial signals.

Ethnopharmacological Relevance: The genus Pteris (Pteridaceae) has been used as a traditional herb for a long time. In particular, Pteris laeta Wall. ex Ettingsh.

Mode of action of elasnin as biofilm formation eradicator of methicillin-resistant .

Biofilm is made up of microbes and their extracellular matrix, making microorganisms highly tolerant, resistant, and resilient to a wide range of antimicrobials. Biofilm treatment with conventional antimicrobial agents can accelerate the evolution and spread of resistance due to the reduced efficacy and increased gene transfer and differentiation within biofilms. Therefore, effective biofilm-targeting compounds are currently highly sought after.

Proteome profiling of evolved methicillin-resistant strains with distinct daptomycin tolerance and resistance phenotypes.

Methicillin-resistant (MRSA) is a highly dangerous pathogen, and daptomycin has been increasingly used to treat its infections in clinics. Recently, several groups have shown that tolerance and resistance of microbes can evolve rapidly under cyclic antibiotic exposure. We have previously shown that the same tolerance and resistance development occurs in MRSA treated with daptomycin in an adaptive laboratory evolution (ALE) experiment.

Mutation in the Two-Component System Regulator YycH Leads to Daptomycin Tolerance in Methicillin-Resistant Staphylococcus aureus upon Evolution with a Population Bottleneck.

Adaptive laboratory evolution (ALE) is a useful tool to study the evolution of antibiotic tolerance in bacterial populations under diverse environmental conditions. The role of population bottlenecks in the evolution of tolerance has been investigated in Escherichia coli, but not in a more clinically relevant pathogen, methicillin-resistant Staphylococcus aureus (MRSA). In this study, we used ALE to evolve MRSA under repetitive daptomycin treatment and incorporated population bottlenecks following antibiotic exposure.

Elasnin Effectively Eradicates Daptomycin-Resistant Methicillin-Resistant Staphylococcus aureus Biofilms.

Elasnin is a recently reported antibiofilm agent that is effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, we observed that elasnin has a superior activity in eradicating daptomycin-resistant MRSA strain biofilm, with a lower minimum biofilm eradication concentration (MBEC) value of 0.625 μg/mL, compared to 2.

Proteomics in antibiotic resistance and tolerance research: Mapping the resistome and the tolerome of bacterial pathogens.

Antibiotic resistance, the ability of a microbial pathogen to evade the effects of antibiotics thereby allowing them to grow under elevated drug concentrations, is an alarming health problem worldwide and has attracted the attention of scientists for decades. On the other hand, the clinical importance of persistence and tolerance as alternative mechanisms for pathogens to survive prolonged lethal antibiotic doses has recently become increasingly appreciated. Persisters and high-tolerance populations are thought to cause the relapse of infectious diseases, and provide opportunities for the pathogens to evolve resistance during the course of antibiotic therapy.

Proteomics and Transcriptomics Uncover Key Processes for Elasnin Tolerance in Methicillin-Resistant Staphylococcus aureus.

Elasnin is a new antibiofilm compound that was recently reported to have excellent activity against methicillin-resistant Staphylococcus aureus (MRSA) biofilms. In this study, we established that elasnin also has antibacterial activity against growing S. aureus planktonic cells.

Novel Daptomycin Tolerance and Resistance Mutations in Methicillin-Resistant Staphylococcus aureus from Adaptive Laboratory Evolution.

It has been shown recently in a number of laboratory evolution experiments that under repetitive antibiotic exposure, bacterial populations can adapt quickly to the treatment condition by becoming tolerant and/or resistant to the drug. The repeated killing and regrowth cycles hasten the selection for tolerant/resistant mutants with survival advantages. Due to the random nature of mutagenesis and the large target size of tolerance mutations, this dynamic evolutionary process appears to be highly unpredictable, generating distinct mutants even under identical, well-controlled laboratory conditions.

Comparative proteomic investigation of multiple methicillin-resistant strains generated through adaptive laboratory evolution.

Recent discoveries indicate that tolerance and resistance could rapidly evolve in bacterial populations under intermittent antibiotic treatment. In the present study, we applied antibiotic combinations in laboratory experiments to generate novel methicillin-resistant strains with distinct phenotypes (tolerance, resistance, and suppressed tolerance), and compared their proteome profiles to uncover the adaptation mechanisms. While the tolerant strains have very different proteomes than the susceptible ancestral strain, the resistant strain largely resembles the ancestral in terms of their proteomes.

Evolution of Bacterial Tolerance Under Antibiotic Treatment and Its Implications on the Development of Resistance.

Recent laboratory evolution studies have shown that upon repetitive antibiotic treatments, bacterial populations will adapt and eventually became tolerant and resistant to the drug. Drug tolerance rapidly evolves upon frequent, intermittent antibiotic treatments, and such emerging drug tolerance seems to be specific to the treatment conditions, complicating clinical practice. Moreover, it has been shown that tolerance often promotes the development of resistance, which further reinforces the need of clinical diagnostics for antibiotic tolerance to reduce the occurrence of acquired resistance.

Proteomic Study of the Survival and Resuscitation Mechanisms of Filamentous Persisters in an Evolved Escherichia coli Population from Cyclic Ampicillin Treatment.

Through adaptive laboratory evolution (ALE) experiments, it was recently found that when a bacterial population was repetitively treated with antibiotics, they will adapt to the treatment conditions and become tolerant to the drug. In this study, we utilized an ampicillin-tolerant population isolated from an ALE experiment to study the mechanisms of persistence during ampicillin treatment and resuscitation. Interestingly, the persisters of this population exhibit filamentous morphology upon ampicillin treatment, and the filaments are getting longer over time.

Proteomic Investigation of Tolerant Populations from Cyclic Antibiotic Treatment.

Persisters are a subpopulation of cells that have enhanced abilities to survive antibiotics and other stressful conditions. Recently, it was found that when persisters were repeatedly regrown and retreated with the same antibiotic for several cycles, the new population will become tolerant to the drug. In this study, we applied such cyclic antibiotic treatment on populations using different classes of antibiotics (ampicillin, ciprofloxacin, and apramycin) during the exponential phase.

Application of proteomics in studying bacterial persistence.

Persisters, a small subpopulation of bacterial cells that can survive antibiotic treatment due to transient growth inhibition, pose a serious threat in clinics. Given the nature of persistence as an emergent property of a biological network, proteomics is well-suited to study this phenomenon. Areas covered: In this review, we introduce the phenomenon of bacterial persistence, review previous proteomics studies on persisters, discuss challenges in studying persisters by proteomics, and provide future perspectives in applying proteomics to study persisters.

Specific Enrichment and Proteomics Analysis of Escherichia coli Persisters from Rifampin Pretreatment.

Bacterial persisters, a dormant and multidrug tolerant subpopulation that are able to resuscitate after antibiotic treatment, have recently received considerable attention as a major cause of relapse of various infectious diseases in the clinic. However, because of their low abundance and inherent transience, it is extremely difficult to study them by proteomics. Here we developed a magnetic-beads-based separation approach to enrich Escherichia coli persisters and then subjected them to shotgun proteomics.