Aug 2026· ChemBioChem· Vol 27· 0 citations· 73 references
Medicine
TL;DR
Flow cytometry is used to quantify the binding of vancomycin=fPep conjugates to S. aureus clinical isolates and will assist in future studies to understand how attached fPeps and other immune signalling cargoes can stimulate innate immune cell activation leading to bacterial phagocytosis.
Abstract
Staphylococcus aureus strains have emerged with resistance mechanisms that reduce the efficacy of last resort antibiotics and evade the immune system. One strategy to combat antimicrobial resistance is to modulate host immunity to eliminate infections more effectively. This has led to the development of immunotherapeutics consisting of vancomycin conjugated to formyl peptides (fPeps), with vancomycin targeting the cell wall and the fPeps engaging host innate immunity. Here, we used flow cytometry to quantify the binding of vancomycin=fPep conjugates to S. aureus clinical isolates. This revealed reduced binding of vancomycin=fPeps compared to vancomycin alone and quantified the interaction between the conjugates and the bacterial cell surface, which is important to quantify to then control the chemotactic gradient established by the fPep cargo. The direct antimicrobial activity of these conjugates was also reduced when compared to vancomycin, reflecting the reduced binding of these conjugates to S. aureus. This flow cytometry method allows quantification of vancomycin=fPep binding to bacteria and will assist in future studies to understand how attached fPeps and other immune signalling cargoes can stimulate innate immune cell activation leading to bacterial phagocytosis.
Findings identify cyclotide grafting as a strategy to improve peptide stability and intracellular delivery, and support MCo-KTR2 as a scaffold for further optimization against intracellular MRSA infections.
Álvaro Mourenza, Jesús Llano-Verdeja, Pablo Castañera et al.· Molecular Biomedicine· 0 citations
Findings position resveratrol-antibacterial peptide mimic conjugates as a promising antimicrobial candidate for combating MRSA-associated wound infections and provide valuable insights for the development of novel antimicrobial agents.
Huixiao Fu, Jun-Hang Zhang, Wen-Qiang Huang et al.· European journal of medicina...· 0 citations
Bacterial infections associated with biofilms continue to be significant clinical problem due to their antibiotic resistance and immunosuppressive capabilities. The recent evidence indicates that the immune checkpoint signaling (PD-1/PD-L1) is involved in the immune impairment in chronic biofilm infections. The study examined the importance of such pathways and whether immune checkpoint inhibitors (ICIs) can be used with antibiotics to enhance the ability to eliminate bacteria and rebuild immune functions. Biofilms of Staphylococcus aureus and Pseudomonas aeruginosa in vitro also were developed and co-cultured with human peripheral blood mononuclear cells (PBMCs). They compared the following four groups: control, ciprofloxacin, antibodies against anti-PD-1/PD-L1 alone and the combination of these two types of antibodies. The crystal violet staining and the confocal microscopy method were used as methods of assessing biofilm biomass, whereas colony-forming unit (CFU) counts were used as the method of measuring viable bacteria. The flow cytometry analysis of PD-1/PD-L1 on T cells was complemented by the analysis of gene expression by qRT-PCR and the level of cytokines by ELISA. Results: Combination therapy yielded the best effect as it decreased biofilm biomass up to 70% in comparison with 35-45% reductions using one of the treatments. Bacterial viability in combination group was also much worse compared to monotherapy groups. Also, the PD-1/PD-L1 on the CD4+ and CD8+ T cells were significantly lowered, as well as TNF-a and IFN-g were elevated and IL-10 was lowered, with a shift up the pro-inflammatory immune response. These results indicate that immune checkpoint blockade is potentially able to augment antibiotic effects against infections caused by biofilms by reversing immunosuppression caused by infection. This integrated approach could be an effective treatment option against chronic and antimicrobial-resistant bacterial infections, but additional in vivo research is necessary to determine the effectiveness of the approach, the optimal dose level, and safety.
Zahraa Mushreq Hadi Khorsheed· Al-Kufa University Journal f...· 0 citations
Staphylococcus aureus
is a common human pathobiont whose nasal colonization represents a major risk factor for subsequent infection. The prevalence of antimicrobial resistance, coupled with antibiotic-induced microbiota perturbation, has rendered
S. aureus
-associated infections increasingly difficult to treat. Commensal bacteria have emerged as potential modulators of both host immune responses and pathogen pathogenesis; however, whether they can act as therapeutic adjuvants to enhance treatment outcomes in
S. aureus-
associated infections remains unclear. Here, we assess the efficacy of commensal bacteria as an adjuvant therapeutic strategy.
Using A549 Dual™ reporter cells, we demonstrate that commensals and pathobionts elicit distinct activation profiles of NF-κB and interferon regulatory factor (IRF) signaling pathways and differential IL-8 production. In a 3D humanized airway tissue model,
D. pigrum
significantly enhanced antibiotic-mediated reduction of
S. aureus
survival relative to antibiotic treatment alone (
D. pigrum
KPL1914: 37.3% reduction, 95% CI 2.0–72.6%,
P
adj
= 0.0340;
D. pigrum
AMBR11: 48.1% reduction, 95% CI 2.3–93.9%,
P
adj
= 0.0356), while preserving barrier integrity and augmenting pro-inflammatory cytokine responses. However, the loss of efficacy with heat-killed
D. pigrum
indicates that viable bacteria and active host- and/or pathobiont-directed interactions are required to mediate its anti-
S. aureus
effects. Dual RNA-seq transcriptomic analysis revealed enrichment of host inflammatory pathways and reduction of
S. aureus
pathogenic potential during
D. pigrum
antibiotic adjuvant treatment in the airway tissue model. Furthermore, co-culture experiments revealed that
D. pigrum
constrains core metabolic pathways in
S. aureus
.
These findings demonstrate that
D. pigrum
limits
S. aureus
through both host immune modulation and direct suppression of bacterial pathogenesis and adaptive fitness, supporting its potential as a microbiota-based therapeutic adjuvant to enhance antibiotic efficacy against
S. aureus
-associated infections.
Chun-Chi Chang, Tomas Demeter, A. Gómez-Mejia et al.· Microbiome· 1 citation
The formation of Pseudomonas aeruginosa (P. aeruginosa) biofilm significantly enhances bacterial resistance to antimicrobial agents and escape from the host immune system, making the treatment of related infections considerably more challenging. As a potential approach for anti-biofilm strategies, the inhibition of lectins often relies on multivalent interactions to enhance binding affinity between the inhibitor and its target. In this study, targeting the P. aeruginosa lectin LecA, we constructed a polyethylene glycol-based multivalent galactoside, termed 4-Arm-PEG-Gal, by modifying the termini of 4-Arm-PEG with galactosides specific to LecA. The results indicate that 4-Arm-PEG-Gal significantly disrupts mature biofilm and is specifically recognized by the lectin LecA. Compared to the use of antibiotics alone, the combination of 4-Arm-PEG-Gal and TOB reduces antibiotic usage by 75% and additionally eradicates 73% of the bacteria within the biofilm. Furthermore, in a model of chronic lung infection, the combination of 4-Arm-PEG-Gal and TOB cleared all bacteria from the lungs, significantly reduced the secretion of TNF-α and IL-6 in the lungs, and effectively ameliorated lung damage caused by bacterial infection.
Chen-Xiao Wan, Xiaoyan Ju, Mei-Yun Ma et al.· Journal of materials chemist...· 0 citations
Nanozymes with peroxidase-like activity have been identified as promising nanomaterials against antimicrobial resistance. However, their in vivo efficacy is significantly limited due to the lack of bacterial targeting ability. Furthermore, the substantial accumulation of nanozymes in nontarget tissues raises concerns of potential nanotoxicity. Here, we report a single-atom nanozyme (mFeP‑gCBD) by coupling ferriporphyrin containing monocarboxyphenyl (mFeP) and cell wall binding domain of endolysin from Staphylococcus aureus phage via a bioorthogonal reaction to achieve targeted catalytic elimination of methicillin-resistant Staphylococcus aureus (MRSA). This nanoplatform can actively recognize MRSA in the infection microenvironment and generate high intensity of reactive oxygen species through its intrinsic peroxidase-like activity, ultimately destroying the structure and biofilm of MRSA. Experimental results demonstrate that mFeP‑gCBD displays 20 times reduction in the effective antibacterial dose compared to untargeted mFeP. In an acute otitis media model infected with MRSA, 2 µg mL- 1 of mFeP‑gCBD significantly alleviates inflammation in the middle ear cavity and recovers mouse auditory thresholds. Remarkably, such a low applied dosage avoids dysbiosis of the commensal bacteria community and systemic toxicity. This work provides a modular design strategy for nanozymes with bacterial targeting capacity.
Bin Hong, Jie Wang, Bing Hu et al.· Small· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
