Elisabet Bjånes

Povidone iodine (PVP-I) is a widely used topical antiseptic with broad antimicrobial activity, but its clinical utility can be limited by skin irritation, slow drying, and persistent staining of skin, textiles, and surfaces. Here, we evaluated reformulated molecular iodine (I ₂ ) products as potential non-staining alternatives with retained or enhanced antimicrobial efficacy. Three I ₂ formulations (soak, nasal antiseptic, and hand ointment) were tested against 17 clinically relevant bacterial and fungal pathogens, including multidrug-resistant organisms and emerging nosocomial pathogens. Antimicrobial performance was assessed by quantitative kill assays, textile staining studies, and persistence testing on dried surfaces. All three I ₂ formulations demonstrated broad-spectrum activity against all organisms tested, with rapid 3–4 log ₁₀ reduction in colony-forming units (CFUs) or >99.9% killing commonly achieved within 15 s; selected fungal species required longer contact times or higher concentrations for maximal activity. Potent activity was observed against major healthcare-associated bacterial pathogens, including Staphylococcus aureus , Enterococcus faecalis , Klebsiella pneumoniae , and Pseudomonas aeruginosa , as well as fungal pathogens including Candida albicans and Candidozyma auris . Compared with PVP-I, I ₂ exhibited minimal residual staining and was readily removed from porous hospital textiles after brief water rinsing. Surface persistence studies further demonstrated sustained antimicrobial activity after drying. These findings indicate that I ₂ retains the broad-spectrum efficacy of traditional iodophors while offering practical advantages in material compatibility and reduced residual staining. I ₂ formulations may, therefore, represent useful alternatives for topical antisepsis and environmental decontamination in high-throughput healthcare settings where both antimicrobial performance and staining-related costs are important considerations.

It remains unclear why vaccines targeting prominent microbial virulence factors often fail in clinical trials. Because microbial virulence depends on interaction with the host immune system, we investigated how changes in host immune function alter vaccine efficacy. Using a vaccine against Staphylococcus aureus α-toxin (Hla), which targets host metalloprotease ADAM10 on myeloid cells, we show that Hla virulence is reduced in aged mice due to diminished ADAM10 activity and impaired myeloid cell function. Depletion of myeloid cells with cyclophosphamide in young mice similarly reduced toxin virulence. Immunization against Hla conferred strong protection against S . aureus infection in young but not aged mice. These findings indicate that pathogenic functions of microbial factors characterized in immunocompetent young animals may not predict virulence or vaccine efficacy in immunocompromised hosts. These findings underscore the need to account for host immune status in the development and evaluation of vaccines targeting microbial virulence factors.

Klebsiella pneumoniae (Kp) is a leading cause of hospital- and community-acquired infections and is increasingly resistant to last-line antibiotics, positioning it as a World Health Organization-designated priority pathogen. Vaccine development has been hindered by the extensive diversity of Kp exopolysaccharide capsules. We developed a cellular nanoparticle (CNP) platform in which bacterial outer membrane vesicles (OMVs) are stably coated onto a STING (stimulator of interferon genes)-adjuvanted nanoparticle core (CNP-KpSTING). The resulting ∼100-nm nanoparticles are homogenous and optimized for recruitment and activation of antigen-presenting cells in draining lymph nodes. CNP-KpSTING vaccination elicited robust antibody responses, enhanced neutrophil-mediated bacterial clearance, and conferred cross-protection against heterologous Kp capsule types in vitro and in lethal pneumonia models. Passive transfer of post-vaccination sera reduced bacterial burden and inflammatory cytokines in the lungs of infected mice. These findings establish CNP-KpSTING as a versatile platform that addresses key antigenic barriers inherent to Kp and support OMV-CNPs as a promising foundation for broadly protective vaccines against multidrug-resistant Gram-negative pathogens.

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are a major antimicrobial resistance threat. Although not standard therapy, azithromycin (AZM) displayed potent activity against ESBL E. coli in vitro, ex vivo, and in vivo. AZM demonstrated multi-fold reductions in MIC, bactericidal activity in supplemented mammalian tissue culture media, and enhanced dose-dependent activity with sodium bicarbonate (NaHCO3). AZM also augmented complement-mediated killing in human serum and improved survival by 50% in a murine bloodstream infection model. These findings underscore the need to revisit antibiotic susceptibility testing—incorporating host defense factors and NaHCO3—and suggest AZM merits further clinical evaluation for ESBL E. coli infections.

Multidrug-resistant (MDR) bacterial pneumonias pose a critical threat to global public health. The opportunistic Gram-negative pathogen Pseudomonas aeruginosa is a leading cause of nosocomial-associated pneumonia, and an effective vaccine could protect vulnerable populations, including the elderly, immunocompromised, and those with chronic respiratory diseases. Highly heterogeneous outer membrane vesicles (OMVs), shed from Gram-negative bacteria, are studded with immunogenic lipids, proteins, and virulence factors. To overcome limitations in OMV stability and consistency, we described a believed to be novel vaccine platform that combines immunogenic OMVs with precision nanotechnology—creating a bacterial cellular nanoparticle vaccine candidate (CNP), termed Pa-STING-CNP, which incorporates an adjuvanted core that activates the STING (stimulator of interferon genes) pathway. In this design, OMVs are coated onto the surface of self-adjuvanted STING nanocores. Pa-STING CNP vaccination induced substantial antigen presenting cell recruitment and activation in draining lymph nodes, robust anti-Pseudomonas antibody responses, and provided protection against lethal challenge with the hypervirulent clinical P. aeruginosa isolate PA14. Antibody responses mediated this protection and provided passive immunity against the heterologous P. aeruginosa strain PA01. These findings provided evidence that nanotechnology can be used to create a highly efficacious vaccine platform against high priority MDR pathogens such as P. aeruginosa.

Colistin (COL) is a cationic cyclic peptide that disrupts the membranes of Gram-negative bacteria and is often used as a last resort antibiotic against multidrug-resistant strains. The emergence of plasmid-borne mcr genes, which confer transferable COL resistance, has raised serious concerns, particularly in strains also carrying extended-spectrum β-lactamase and carbapenemase genes. Standard antimicrobial susceptibility testing (AST), performed in enriched bacteriological media, indicates no activity of COL against mcr ⁺ strains, leading to its exclusion from treatment regimens. However, these media poorly reflect in vivo physiology and lack host immune components. Here we show that COL retained bactericidal activity against mcr-1 ⁺ Escherichia coli , Klebsiella pneumoniae , and Salmonella enterica when tested in tissue culture medium containing physiological bicarbonate. COL enhanced serum complement deposition on bacterial surfaces and synergized with human serum to kill pathogens. At clinically achievable concentrations, COL killed mcr-1 ⁺ strains in freshly isolated human blood and was effective as monotherapy in a murine E . coli bacteremia model. These findings suggest that COL, currently dismissed based on conventional AST, may offer clinical benefit against mcr-1 ⁺ infections when evaluated under more physiological conditions — warranting reconsideration in clinical microbiology practices and future trials for high-risk patients.

Background: Phosphoinositide 3-kinase is a potent target for cancer therapy due to its significant role in the regulation of cellular growth and proliferation. Dysregulation of the PI3k signaling cascade can constitutively activate growth pathways to trigger the progression of cancer, resulting in the development of multiple inhibitors as cancer therapeutics. Objectives: The wide array of cells expressing PI3k also include immune cells, and the inhibition of these receptors has shown promise in combating inflammation and infectious disease, a relationship we sought to examine further. Methods: We infected wild-type and PI3kγ knockout murine macrophages as well as PI3kγ inhibitor-treated THP-1 human macrophage-like cells with Staphylococcus aureus and quantified inflammation through gene expression analysis, protein secretion assays, and immunofluorescence imaging. Results: We observed that knockout of PI3kγ in murine macrophages alongside pharmacological inhibition through IPI549 treatment in THP-1 cells led to an NF-κB-driven suppression in transcription and release of inflammatory cytokines upon infection with methicillin-resistant Staphylococcus aureus. We were also able to confirm that this suppression of NF-κB translocation and subsequent decrease in inflammatory cytokine release did not compromise and even slightly boosted the bacterial killing ability. Conclusion: PI3k is primarily targeted for cancer therapies, but further exploration can also be carried out on its potential roles in treating bacterial infection.

Introduction: Healthcare-associated infections (HAIs) pose a significant challenge in acute care hospitals, particularly in intensive care units, due to persistent environmental contamination despite existing disinfection protocols and manual cleaning methods. Current disinfection methods are labor-intensive and often ineffective against multidrug-resistant (MDR) pathogens, highlighting the need for new, automated, hands-free approaches.Methods: This study evaluates the bactericidal efficacy of low concentrations of gaseous ozone (5 ppm) against clinically relevant and often MDR bacteria under various concentrations, contact times, temperatures, and environmental conditions.Results: We observed a 3 log₁₀-fold reduction in Escherichia coli and Salmonella Typhimurium and a 1–2 log₁₀-fold reduction in group A Streptococcus and methicillin-resistant Staphylococcus aureus upon ozone exposure. The bactericidal effect was dose-dependent, with no significant difference between single and repeated exposures. Environmental conditions such as temperature and humidity had minimal impact on low-dose ozone efficacy, with slightly improved bacterial killing at colder temperatures and higher humidity levels. Gaseous ozone also showed significant bactericidal activity against the broad range of Gram-positive and -negative MDR clinical isolates.Discussion: These findings highlight the potential of low-dose gaseous ozone as a versatile, effective, and hands-free disinfectant for healthcare and other settings. Further research is needed to establish long-term safety and efficacy guidelines for its use in occupied spaces and to explore potential synergy with other contemporary disinfection strategies.

Pathogenic bacteria have acquired the ability to resist antibacterial defense mechanisms of the host. Streptococci are common in animal microbiota and include opportunistic pathogens like Group A Streptococcus (GAS) and Streptococcus pneumoniae (pneumococcus). While the conserved streptococcal S protein has been identified as a key factor in GAS virulence, its exact function is unclear. Here, we show that the pneumococcal S protein is crucial for resisting against host-derived antimicrobials by coordinating cell wall modification and repair. Specifically, we show that S proteins are septally localized through their transmembrane domain and contain an extracellular peptidoglycan (PG) binding LysM domain which is required for its function. Protein-protein and genetic interaction studies demonstrate that the pneumococcal S protein directly interacts with a PG synthase, class A penicillin binding protein PBP1a, and the PG deacetylase PgdA. Single-molecule experiments reveal that the fraction of circumferentially moving PBP1a molecules is reduced in the absence of S protein. Consistent with an impaired PBP1a function, streptococci lacking S protein exhibit increased susceptibility to cell wall targeting antibiotics and altered cell morphologies. PG analysis showed reduced N-deacetylation of glycans in the S. pneumoniae S protein mutant, indicating reduced PgdA activity. We show that pneumococci lacking the S protein cannot persist transient penicillin treatment, are more susceptible to the human antimicrobial peptide LL-37 and to lysozyme, and show decreased virulence in zebrafish and mice. Our data support a model in which S proteins regulate PBP1a activity and play a key role in coordinating PG repair and modification. This cell wall ‘sentinel’ control system provides defense against host-derived and environmental antimicrobial attack.