Tissue-adhesive hydrogel–MXene biosensor for in situ intraoral TNF-α detection

Science Advances · 2026-01-16 · 2 citations

Current dental care relies on subjective assessments or sophisticated diagnostics, both struggling to balance efficiency and accuracy. In situ biosensors offer a promising solution for real-time biomarker detection, yet their practical deployment in oral tissue is hindered by challenges in sensitivity, specificity, and stability due to low biomarker concentrations, molecular-level heterogeneity, and dynamic intraoral interactions. Here, we develop a tissue-adhesive hydrogel-MXene (TAHM) biosensor, integrating a graphene/MXene sensing probe, a tissue-adhesive patch, and a selective-permeable hydrogel membrane, for in situ detection of tumor necrosis factor-α, a proinflammatory cytokine. Our TAHM biosensor achieves high sensitivity with a limit of detection of 18.2 femtograms per milliliter, excellent selectivity with an interference coefficient below 7%, and mechanical stability with resistance variation under 0.5% under varying stretch ratio and loading rates. The sensor's performance is further validated through in vitro, in vivo, and ex vivo experiments. The work highlights the potential of in situ biosensor as a transformative tool for real-time oral diagnostics.

Microbicidal mechanisms for light-activated molecular nanomachines in Mycobacterium smegmatis: A model for pathogenic bacteria

OpenNano · 2025-02-25 · 1 citations

= 19.24). These findings suggest that MNMs have the potential to be innovative and sustainable antimicrobial agents for the treatment of pathogenic mycobacterial infections.

<i>Mycobacterium tuberculosis</i> fluorescent and bioluminescent imaging technologies: addressing the issue of sensitivity

Expert Review of Respiratory Medicine · 2025-10-30

INTRODUCTION: (Mtb), is a common cause of death in humans worldwide. The slow growth rate of Mtb (~20 hours) makes progress in research slow and diagnosis difficult. AREAS COVERED: bacteria in mice. Reporter enzyme fluorescence (REF) is a new and very sensitive Mtb imaging technology that uses BlaC, a highly specific surface-localized β-lactamase, in combination with fluorogenic or bioluminescent probes. As such, REF can reduce the threshold to 10-100 bacteria in vivo and detect 10 bacteria within 10 minutes in vitro. EXPERT OPINION: Recombinant reporter systems for imaging bacteria should continue to improve and may reach similar thresholds, but at present, REF remains the most sensitive approach. Furthermore, new more sensitive probes can be readily developed, suggesting that REF will ultimately allow detection of single bacteria in an infected host.

Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

Communications Biology · 2024-08-22 · 4 citations

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections. Use of peptoids to treat a mouse model of respiratory infection for Pseudomonas aeruginosa. Additionally, this study determined the cytotoxic effect of peptoids on several types of respiratory models when compared to traditional cell culture models.

TCA metabolism regulates DNA hypermethylation in LPS and<i>Mycobacterium tuberculosis</i>–induced immune tolerance

Proceedings of the National Academy of Sciences · 2024-09-30 · 24 citations

Severe and chronic infections, including pneumonia, sepsis, and tuberculosis (TB), induce long-lasting epigenetic changes that are associated with an increase in all-cause postinfectious morbidity and mortality. Oncology studies identified metabolic drivers of the epigenetic landscape, with the tricarboxylic acid (TCA) cycle acting as a central hub. It is unknown if the TCA cycle also regulates epigenetics, specifically DNA methylation, after infection-induced immune tolerance. The following studies demonstrate that lipopolysaccharide and Mycobacterium tuberculosis induce changes in DNA methylation that are mediated by the TCA cycle. Infection-induced DNA hypermethylation is mitigated by inhibitors of cellular metabolism (rapamycin, everolimus, metformin) and the TCA cycle (isocitrate dehydrogenase inhibitors). Conversely, exogenous supplementation with TCA metabolites (succinate and itaconate) induces DNA hypermethylation and immune tolerance. Finally, TB patients who received everolimus have less DNA hypermethylation demonstrating proof of concept that metabolic manipulation can mitigate epigenetic scars.

Antiviral Effect of Antimicrobial Peptoid TM9 and Murine Model of Respiratory Coronavirus Infection

Pharmaceutics · 2024-03-27 · 3 citations

-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study, TM9 was effective against three murine coronavirus strains, demonstrating that the therapeutic window is large enough to allow the use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber, and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from the liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Antiviral Effect of Antimicrobial Peptoids and a Murine Model of Respiratory Coronavirus Infection

Preprints.org · 2024-02-22 · 1 citations

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Absolute concentration estimation of COVID-19 convalescent and post-vaccination IgG antibodies

PLoS ONE · 2024-11-01 · 4 citations

Soon after commencement of the SARS-CoV-2 disease outbreak of 2019 (COVID-19), it became evident that the receptor-binding domain of the viral spike protein is the target of neutralizing antibodies that comprise a critical element of protective immunity to the virus. This study addresses the relative lack of information regarding actual antibody concentrations and binding affinities in convalescent plasma (CP) samples from COVID-19 patients and extends these analyses to post-vaccination (PV) samples to estimate protective IgG antibody (Ab) levels. A direct enzyme-linked immunosorbent assay (ELISA) was used to measure IgG anti-spike protein (SP) antibodies (Abs) relative to human chimeric spike S1 Ab standards. Microplate wells were coated with recombinant SP. Affinities of Ab binding to SP were determined by previously described methods. Binding affinities were also determined in an RBD-specific sandwich ELISA. Two indices of protective immunity were determined as permutations of Ab molar concentration divided by affinity as dissociation constant (KD). The range and geometric means of Ab concentrations in 21 CP and 21 PV samples were similar and a protective Ab level of 7.5 μg/ml was determined for the latter population, based on 95% of the normal distribution of the PV population. A population (n = 21) of plasma samples from individuals receiving only one vaccination with the BNT162b2 or mRNA-1273 vaccines (PtV) exhibited a geometric mean Ab concentration significantly (p < 0.03) lower than the PV population. The results of this study have implications for future vaccine development, projection of protective efficacy duration, and understanding of the immune response to SARS-CoV-2 infection.

Author Correction: Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

Communications Biology · 2024-09-13 · 1 citations

Correction to: Communications Biology https://doi.org/10.1038/s42003-024-06725-1, published online 22 August 2024

Microbicidal Mechanisms for Light-Activated Molecular Nanomachines in <i>Mycobacterium smegmatis</i> : A Model for Pathogenic Bacteria

bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-06

Abstract There is a global health crisis of antimicrobial resistance, with over a million deaths annually attributed to antimicrobial-resistant pathogens, and mycobacterial infections are a major cause of antimicrobial-resistant infections, leading to more deaths than any other single infectious agent. Notably, the rise of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains of Mycobacterium tuberculosis led to higher mortality rates and challenge all existing antibiotic regimens. Light-activated molecular nanomachines (MNMs) represent a promising class of broad-spectrum antimicrobial agents that could help counter this rise in antimicrobial resistance. Addressing a key knowledge gap, this study explores the mechanisms of action for MNMs in Mycobacterium smegmatis , a surrogate model for pathogenic mycobacteria. We show that fast rotor MNMs kill up to 97% of M. smegmatis and co-localize with the bacteria as part of their mechanism of action. The ability to translate these observations to pathogenic mycobacteria was demonstrated by the ability of MNMs to kill 93.5% of M. tuberculosis under similar conditions. These findings suggest that MNMs may provide innovative sustainable antimicrobial agents for the treatment of drug-resistant mycobacterial infections. Graphical Abstract Bacteria exposed to MNMs have two distinct outcomes when activated by 365 nm light. Slow motors (MNM 2 and 4) have no rotational action, remains outside the bacteria and have little to no effect on bacterial viability. Whereas fast motors (MNM 1 and 3) co-localize and embed into the bacterial cell wall causing disruptions that lead to a significant reduction in bacterial viability.