Biology subjects

Speck, P.

Publications and source records attributed to Speck, P..

3 recordsLinked to original sources

bioRxiv2026

Injectable Electrospun Hydrogel with Antimicrobial, pH Sensing Nanoparticles for Local Infection Control and Monitoring

Most antimicrobial drug candidates currently in development are derivatives of established antibiotic classes. In contrast, antimicrobial heteroatom-doped carbon quantum dot (COD) nanoparticles vastly differ from their chemical antibiotic counterparts and exhibit potent antibacterial activity and favourable biocompatibility, representing a promising alternative strategy, particularly for topical applications. Here, we report the incorporation of cobalt-doped carbon quantum dots (Co-CODs) into injectable, biocompatible hydrogels capable of both sensing pH and eliminating bacteria. Ultrasmall Co-CODs demonstrated broad-spectrum activity against gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa (PAO1), mediated by membrane hyperpolarisation and reactive oxygen species (ROS) induced membrane damage. The particles showed negligible effect on primary fibroblast and endothelial cell viability at concentrations that were bactericidal to MRSA. Polymeric hydrogels were fabricated via electrospinning of chitosan, polyvinylpyrrolidone (PVP), and polyvinyl alcohol (PVA) polymer blends incorporating Co-COD and pH-responsive HPTS particles. This approach provided accurate measurement of environmental pH within the physiological range observed across healthy and chronic wounds. In vivo, the injectable hydrogels exhibited robust antimicrobial efficacy against MRSA without impairing wound closure relative to untreated controls, while also reducing inflammatory immune responses in infected tissues. Collectively, these findings demonstrate the potential of ultrasmall metal-doped CODs for infection control and their integration into 3D matrices as multifunctional theragnostic platforms. ToC (<60 words describe the main results)Ultrasmall antimicrobial carbon nanoparticles were incorporated into polymeric hydrogels containing a pH-responsive probe. This platform enabled detection across a physiologically relevant pH range of 5.0-6.5, spanning conditions associated with both healthy healing and chronically infected wounds. The hydrogel demonstrated strong antibacterial activity by generating damaging reactive oxygen species, and, in mice, effectively controlled infection while reducing pro-inflammatory immune responses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/736887v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1a52b32org.highwire.dtl.DTLVardef@b6eed2org.highwire.dtl.DTLVardef@1f94143org.highwire.dtl.DTLVardef@12b9ff3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOScheme 1:C_FLOATNO Antimicrobial nanoparticle-doped hydrogel glows in alkaline wound conditions which are representative of chronic infections. Once in the wound bed, the hydrogel removes all MRSA infection, reducing inflammatory macrophage (iNOS) and neutrophil (MPO) populations, and restores healthy wound collagen deposition. C_FIG

bioengineering↗

bioRxiv2026

Impairment of bacteriophage activity in blood: a case study revealing constraints in phage isolation and translation

BackgroundPhage therapy is increasingly considered a promising alternative for treating multidrug-resistant (MDR) infections. However, its clinical application remains limited by challenges in isolating effective phages against resistant clinical strains and by the limited ability of in vitro assays to predict performance in real biological environments. While biological matrices are known to influence phage activity, these effects are not well characterised. MethodsA phage-resistant Pseudomonas aeruginosa isolate from a patient with recurrent MDR urinary tract infection was used as the model organism. Conventional isolation methods failed to recover effective phages, leading to the development of TEASER-i (Transient EDTA- and Ion-Assisted Sequential Enrichment & Recovery). Recovered phages were characterised using adsorption assays, one-step growth kinetics, and time-kill experiments. Their antibacterial activity was evaluated both in vitro and in ex vivo human matrices (whole blood, serum, plasma, and urine). Phage efficacy was quantified using maximum log reduction (Emax), area under the curve (AUC), and phage-to-bacteria ratio (PBR). ResultsA novel TEASER-i method optimised for difficult-to-treat Gram-negative infections, enabled recovery of a functionally effective Osewage-derived P. aeruginosa phage, which outperformed a Ourine-derived P. aeruginosa phage that showed slower replication and lower burst size. Phage activity varied significantly in blood, serum, and plasma. Urine supported the most sustained antibacterial effect. In many cases, early bacterial reduction was followed by regrowth. Sustained activity was associated with maintenance of favourable PBR values, while negative PBR corresponded to treatment failure. At 96 h, only two conditions maintained favourable phage load (log 10 PBR > 0): the S. aureus phage in urine (+1.66) and the sewage-derived P. aeruginosa phage in serum (+1.32). ConclusionsPhage efficacy depends not only on intrinsic lytic capacity but also on the ability to persist and amplify within specific biological environments. Conventional isolation and in vitro screening may therefore overestimate therapeutic potential. Combining optimised isolation strategies with ex vivo evaluation provides a more realistic framework for phage selection and clinical translation.

microbiology↗

bioRxiv2026

Ionic regulation of Gram-positive phage adsorption governs host range and improves phage isolation efficiency

Antimicrobial-resistant Staphylococcus aureus and S. epidermidis remain major causes of invasive infection, yet isolation of therapeutically robust lytic phages targeting Gram-positive pathogens is often constrained by adsorption barriers imposed by thick peptidoglycan cell walls. We demonstrate that these limitations are primarily methodological. By optimising the ionic microenvironment during isolation through divalent cation supplementation (10 mM CaCl2 and MgSO4), controlled enrichment, phage polyclonal mixtures, and limited lysozyme-assisted release, we recovered 28 genomically distinct lytic phages compared with six obtained using conventional protocols. Host-range profiling across 103 clinical isolates showed broad infectivity, with 51.7% of interactions supporting high-efficiency infection and multiple phages exhibiting cross-species activity. Ion-supplemented adaptive passaging restored and expanded lytic capacity against resistant strains within five rounds. These findings show that ionic regulation of adsorption reshapes Gram-positive phage-host dynamics and provide a scalable framework for precision targeting of resistant Staphylococcus infections.

microbiology↗