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Neutrophils are predominant immune cells that protect the human body against infections by deploying sophisticated antimicrobial strategies including phagocytosis of bacteria and neutrophil extracellular trap (NET) formation. Here, we provide an overview of the mechanisms by which neutrophils kill exogenous pathogens before we focus on one particular weapon in their arsenal: the generation of the oxidizing hypohalous acids HOCl, HOBr and HOSCN during the so-called oxidative burst by the enzyme myeloperoxidase. We look at the effects of these hypohalous acids on biological systems in general and proteins in particular and turn our attention to bacterial strategies to survive HOCl stress. HOCl is a strong inducer of protein aggregation, which bacteria can counteract by chaperone-like holdases that bind unfolding proteins without the need for energy in the form of ATP. These chaperones are activated by HOCl through thiol oxidation (Hsp33) or N-chlorination of basic amino acid side-chains (RidA and CnoX) and contribute to bacterial survival during HOCl stress. However, neutrophil-generated hypohalous acids also affect the host system. Recent studies have shown that plasma proteins act not only as sinks for HOCl, but get actively transformed into modulators of the cellular immune response through N-chlorination. N-chlorinated serum albumin can prevent aggregation of proteins, stimulate immune cells, and act as a pro-survival factor for immune cells in the presence of cytotoxic antigens. Finally, we take a look at the emerging role of HOCl as a potential signaling molecule, particularly its role in neutrophil extracellular trap formation.

Livestock farms are at risk of exposure to various environmental pollutants, particularly airborne viruses that can cause infectious diseases. Hydroxyl radicals (•OH) are well-known for their strong bactericidal and virucidal properties and are widely applied in disinfection processes. However, their efficacy is significantly diminished in the presence of organic substances. This study investigated the bactericidal effects of hydroxyl radicals generated from hypochlorous acid (HOCl) under UV irradiation and evaluated their resistance to quenching by airborne organic matter. Rose Bengal (RNO) dye was used as a probe to detect •OH radical generation, while yeast extract served as a representative organic contaminant. RNO bleaching efficiency increased in a concentration-dependent manner under UV irradiation, confirming the formation of hydroxyl radicals. However, in the presence of yeast extract, this bleaching effect was drastically reduced, indicating that organic compounds can interfere with radical activity. The bactericidal effects of UV light and HOCl were independently evaluated using Salmonella as a model organism. The presence of organic matter significantly reduced the bactericidal efficacy of both UV and HOCl treatments when applied separately. In contrast, combined exposure to HOCl and UV irradiation demonstrated a 10% increase in bacterial reduction and halved the required exposure time, regardless of HOCl concentration. These findings highlight the synergistic bactericidal potential of HOCl and UV irradiation and support their applicability in airborne bacterial disinfection under realistic environmental conditions.

Ferroptosis is a way of cell death mainly due to the imbalance between the production and degradation of lipid reactive oxygen species, which is closely associated with various diseases. Endogenous hypochlorous acid (HOCl) mainly produced in mitochondria is regarded as an important signal molecule of ferroptosis. Therefore, monitoring the fluctuation of endogenous HOCl is beneficial to better understand and treat ferroptosis-related diseases. Inspired by the promising aggregation-induced emission (AIE) properties of tetraphenylethene (TPE), herein, we rationally constructed a novel AIE-based fluorescent probe, namely QTrPEP, for HOCl with nice mitochondria-targeting ability and high sensitivity and selectivity. Probe QTrPEP consisted of phenylborate ester and the AIE fluorophore of quinoline-conjugated triphenylethylene (QTrPE). HOCl can brighten the strong fluorescence through a specific HOCl-triggered cleavage of the phenylborate ester bond and release of QTrPE, which has been demonstrated by MS, HPLC, and DLS experiments. In addition, combining QTrPE-doped test strips with a smartphone-based measurement demonstrated the excellent performance of the probe to sense HOCl. The obtained favorable optical properties and negligible cytotoxicity allowed the use of this probe for tracking of HOCl in three different cells. In particular, this work represents the first AIE-based mitochondria-targeting fluorescent probe for monitoring the fluctuation of HOCl in ferroptosis.

Effective infection control measures are crucial for limiting pathogen transmission, including aerosol infections. Several instances of the use of hypochlorous acid solution spray to inactivate airborne viruses have been reported. However, its effectiveness in controlling infections in aerosol transmission scenarios remains unclear. We evaluated the efficacy of gaseous hypochlorous acid [HOCl (g) ], which is safe for occupied environments, in infection control. Exposure to 10–20 ppb HOCl (g) for several seconds significantly reduced the infectivity of aerosolised H1N1 influenza A virus in water-rich droplets by 2.09–2.79 logs. However, no significant reduction occurred in dry aerosols after water evaporation. A stronger inactivation effect was noted at 50% compared to 30% relative humidity, with a 3.06-fold increase in effectiveness. Comparative analysis with a reactive oxygen species gas (O₃), possessing lower liquid-phase solubility than HOCl (g) , suggested that aerosol water content facilitates HOCl-mediated virucidal activity. Viral infectivity decreased by 2.34 logs under 20-ppb conditions, even in the presence of 0.3% mucin. These findings underscore the effectiveness of HOCl (g) against aerosolised H1N1 influenza A virus and its potential for infection control.

Biofilm formation causes prolonged wound infections due to the dense biofilm structure, differential gene regulation to combat stress, and production of extracellular polymeric substances. Acinetobacter baumannii , Staphylococcus aureus , and Pseudomonas aeruginosa are three difficult-to-treat biofilm-forming bacteria frequently found in wound infections. This work describes a novel wound dressing in the form of an electrochemical scaffold (e-scaffold) that generates controlled, low concentrations of hypochlorous acid (HOCl) suitable for killing biofilm communities without substantially damaging host tissue. Production of HOCl near the e-scaffold surface was verified by measuring its concentration using needle-type microelectrodes. E-scaffolds producing 17, 10 and 7 mM HOCl completely eradicated S. aureus , A. baumannii , and P. aeruginosa biofilms after 3 hours, 2 hours, and 1 hour, respectively. Cytotoxicity and histopathological assessment showed no discernible harm to host tissues when e-scaffolds were applied to explant biofilms. The described strategy may provide a novel antibiotic-free strategy for treating persistent biofilm-associated infections, such as wound infections.

Background Laser resurfacing treatments have revolutionized dermatological procedures by improving skin texture, tone, and quality. Effective periprocedural care remains essential to reduce side effects, support healing, and optimize aesthetic outcomes. Hypochlorous acid (HOCl), a naturally occurring oxidant with anti‐inflammatory and antimicrobial properties, has demonstrated efficacy in promoting wound healing and minimizing scarring. Aim To evaluate the use of stabilized HOCl mist in the periprocedural care of patients undergoing laser resurfacing. Methods Ten patients underwent treatment with UltraClear, CO2RE, and/or GentleMax Pro laser devices. Stabilized HOCl mist was applied before and after the procedure, with continued application twice daily for 1 week posttreatment. Follow‐up assessments at 1–3 weeks and 1–3 months post‐procedure included clinical photography, tolerability evaluation, and aesthetic outcome assessment. Outcomes measured included Clinician Erythema Assessment (CEA), 4‐point Edema Scale, Investigator Global Assessment of Pigmentation Scale (IPA), and Global Aesthetic Improvement Scale (GAIS). Statistical analysis was performed using the Friedman and Wilcoxon signed‐rank tests. Results HOCl mist was associated with accelerated recovery, including a noticeable reduction in erythema and pigmentation. Statistically significant improvements were observed in CEA (p = 0.007) and IPA (p = 0.012) scores, indicating reduced clinical severity and pigment alteration. Edema and GAIS scores showed no statistically significant change. Conclusion Stabilized HOCl mist is well‐tolerated and may significantly aid post‐procedural recovery by minimizing side effects and reducing discomfort. Results support the potential role of stabilized HOCl mist as a beneficial adjunct in post‐laser skincare, contributing to faster healing, reduced inflammation, and enhanced cosmetic results.

As the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen ( 1 O 2 ) species. Studies on both cells and animals demonstrate successful 1 O 2 -mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation. Enzymatic reactions caused by neutrophils can cause the elevation of reactive oxygen species (ROS) in tumour tissue, Here, the authors, inspired by the neutrophils, design and test a synthetic cascade reaction which turns ROS into singlet oxygen and demonstrate the application of the designed nanoparticle

Phagocytes destroy pathogens by trapping them in a transient organelle called the phagosome, where they are bombarded with reactive oxygen species (ROS) and reactive nitrogen species (RNS). Imaging reactive species within the phagosome would directly reveal the chemical dynamics underlying pathogen destruction. Here we introduce a fluorescent, DNA-based combination reporter, cHOClate, which simultaneously images hypochlorous acid (HOCl) and pH quantitatively. Using cHOClate targeted to phagosomes in live cells, we successfully map phagosomal production of a specific ROS, HOCl, as a function of phagosome maturation. We found that phagosomal acidification was gradual in macrophages and upon completion, HOCl was released in a burst. This revealed that phagosome–lysosome fusion was essential not only for phagosome acidification, but also for providing the chloride necessary for myeloperoxidase activity. This method can be expanded to image several kinds of ROS and RNS and be readily applied to identify how resistant pathogens evade phagosomal killing. The combination of multiple fluorophores on a hybridized DNA scaffold enables the development of the reporter cHOClate, which is used to simultaneously and quantitatively image hypochlorous acid (HOCl) and pH during phagosome maturation.

Hypochlorous acid (HOCl) is generated in the immune system to kill microorganisms. In Escherichia coli, a hypochlorite-specific transcription regulator, HypT, has been characterized. HypT belongs to the LysR-type transcriptional regulator (LTTR) family that contains a DNA-binding domain (DBD) and a regulatory domain (RD). Here, we identified a hypT gene from Salmonella enterica serovar Typhimurium and determined crystal structures of the full-length HypT protein and the RD. The full-length structure reveals a type of tetrameric assembly in the LTTR family. Based on HOCl-bound and oxidation-mimicking structures, we identified a HOCl-driven methionine oxidation mechanism, in which the bound HOCl oxidizes a conserved methionine residue lining the putative ligand-binding site in the RD. Furthermore, we proposed a molecular model for the oxidized HypT, where methionine oxidation by HOCl results in a conformational change of the RD, inducing a counter rotation of the DBD dimers. Target genes that are regulated by HypT and their roles in Salmonella were also investigated. DNase I footprinting experiments revealed a DNA segment containing two pseudopalindromic motifs that are separated by ∼100 bp, suggesting that only the oxidized structure makes a concomitant binding, forming a DNA loop. An understanding of the HypT-mediated mechanism would be helpful for controlling many pathogenic bacteria by counteracting bacterial HOCl defense mechanisms.

The lack of tools to monitor the dynamics of (pseudo)hypohalous acids in live cells and tissues hinders a better understanding of inflammatory processes. Here we present a fluorescent genetically encoded biosensor, Hypocrates, for the visualization of (pseudo)hypohalous acids and their derivatives. Hypocrates consists of a circularly permuted yellow fluorescent protein integrated into the structure of the transcription repressor NemR from Escherichia coli . We show that Hypocrates is ratiometric, reversible, and responds to its analytes in the 10 6  M −1 s −1 range. Solving the Hypocrates X-ray structure provided insights into its sensing mechanism, allowing determination of the spatial organization in this circularly permuted fluorescent protein-based redox probe. We exemplify its applicability by imaging hypohalous stress in bacteria phagocytosed by primary neutrophils. Finally, we demonstrate that Hypocrates can be utilized in combination with HyPerRed for the simultaneous visualization of (pseudo)hypohalous acids and hydrogen peroxide dynamics in a zebrafish tail fin injury model. There are a lack of tools to study the dynamics of (pseudo)hypohalous acids in live cells. Here the authors report a genetically encoded fluorescent biosensor, Hypocrates, for (pseudo)hypohalous acids and their derivatives which they use in cells and in a zebrafish tail fin injury model.