Antimicrobial Toxicity Research Articles

Green and chemical synthesis of iron oxide nanoparticles: Comparative study for antimicrobial activity and toxicity concerns

Infections caused by multidrug-resistant bacteria in healthcare settings highlight the critical need for robust infection control strategies and effective antimicrobial stewardship. This was further emphasized by the COVID-19 pandemic. This necessitates developing more effective antimicrobial agents. Iron oxide nanoparticles (IONPs) were reported to be biocompatible and possess a broad-spectrum antimicrobial activity with less susceptibilty of developing microbial resistance. Chemical synthesis is employed for industrial manufacture of IONPs. However, concerns about potential toxicity associated with chemical synthesis have led to a preference for green synthesis approaches, despite ongoing debates regarding their cytotoxicity. According to the authors' knowledge, the impact of synthesis methodology on the antimicrobial activity and cytotoxicity of IONPs has not been previously studied. Therefore, the current study is considered the first attempt to assess and compare the toxicity and antimicrobial effect of IONPs synthesized using different methodologies (green versus chemical synthesis) while correlating these effects to the physicochemical properties of IONPs. Additionally, this study addresses for the first time the disturbance of the microbial antioxidant defense system in multidrug-resistant bacteria after their exposure to IONPs. Both types of IONPs effectively eradicated SARS-CoV-2, and multidrug-resistant bacteria: S. aureus, and E. Coli, in addition, both disrupted the antioxidant bacterial defense mechanism, indicating that reactive oxygen species play a significant role in their antimicrobial activities. Chemically synthesized IONPs showed superior antimicrobial activity to those produced by green methods and in-vivo study demonstrated their greater compatibility with skin and eyes. Therefore, chemically synthesized IONPs might be used as a disinfectant in healthcare settings.

Differentiation of antimicrobial toxicity and sepsis-induced disseminated intravascular coagulation in an orthopedic burn patient in India: a case report

Differentiation of antimicrobial toxicity and sepsis-induced disseminated intravascular coagulation in an orthopedic burn patient in India: a case report

Green Synthesis of Silver Nanoparticles Using Doxycycline: Evaluation of Antimicrobial Potential and Organ-specific Toxicity

Silver nanoparticles (Ag-NPs) have wide applicability as antimicrobial, biomedical, and anti-cancer drug delivery systems. This study aimed to synthesize Ag-NPs using green methodology to assess their antimicrobial properties and toxicity. Ag-NPs were prepared using doxycycline, an antibiotic serving as a reducing and capping agent. The synthesized Ag-NPs were characterized by ultraviolet-visible spectrophotometry, X-ray diffraction, scanning electron microscopy, and Fourier-transform infrared spectrometry. The antimicrobial efficacy of doxycycline-mediated Ag-NPs was assessed on Candida species in vitro and for toxicity in male albino mice in vivo. The Ag-NPs showed a surface plasmon resonance at 411 nm, indicating a 90 nm average size and spherical shape. Toxicity was tested on mouse organs (liver, kidney, spleen, heart and stomach) using three Ag-NP doses (50, 100, 200 mg/kg) over 14 days. The synthesized Ag-NPs produced large inhibition zones against two well-known fungal species, C. albicans and C. tropicalis, demonstrating their antimicrobial potential. The Ag-NPs showed varying degrees of toxicity in different mouse organs, depending on the administered dose, with more pronounced adverse effects observed at higher concentrations. Periodic administration of Ag-NPs at low-dose volumes holds promise as a safe approach to their use as antimicrobial agents. Low-dose Ag-NPs are minimally toxic and show strong antimicrobial efficacy.

Effective combinations of silver nanoparticles and antimicrobial peptides against antibiotic-resistant bacteria

BACKGROUND: The problem of constantly growing resistance of microorganisms to the antibiotics used forces scientists to constantly search for new antimicrobial agents. AIM: To study the antimicrobial activity and toxicity of silver nanoparticles and antimicrobial peptides with a β-hairpin structure, and to characterize their combined antimicrobial action. MATERIALS AND METHODS: The antimicrobial activity of silver nanoparticles and antimicrobial peptides against antibiotic-resistant bacteria was assessed by serial dilutions in a liquid nutrient medium, and the combined antimicrobial activity – by serial dilutions according to the “checkerboard” method. The toxicity of the substances to human cells was determined using a hemolytic test. RESULTS: The studied silver nanoparticles have pronounced antimicrobial activity and low toxicity to human erythrocytes. Silver nanoparticles containing acetylcysteine are more active against gram-negative bacteria than against gram-positive ones. Synergism of the antibacterial action was detected with the combined use of silver nanoparticles stabilized with sodium oleate and protegrin-1. A synergistic antimicrobial effect was also noted for combinations of silver nanoparticles containing acetylcysteine with protegrin-1, ricaecilin and shuchin-4. CONCLUSIONS: Effective combinations of silver nanoparticles and antimicrobial peptides have been identified that act synergistically against antibiotic-resistant bacterial strains, i.e. they multiply the effect of each other. These combinations can be used as prototypes for the development of antibacterial drugs.

Synthesis and characterization of new antimicrobial peptides derived from Temporin F.

Antimicrobial peptides (AMPs) are a promising source of new compounds against resistant bacteria. Temporins are a class of AMPs found on the amphibian Rana temporaria and show activity against Gram-positive and Gram-negative bacteria. There are few studies on how these antimicrobials have been used, but new Temporin-F derivatives were engineered with Lys-substitutions to assess the impact of the net charge on antimicrobial activity and toxicity. We demonstrated through some assays that it is possible to increase the antibacterial activity while maintaining a reduced peptide hemolytic activity with specific substitutions. Our lead synthetic peptide, G6K-Temporin F, has shown higher antimicrobial activity against Gram-negative and Gram-positive bacteria in vitro (MIC range 2 to 32 μmol L-1), with low hemolytic activity maintained, resulting in an increase in the therapeutic window (TW), of 12.5. Also, it showed more resistant to enzymatic degradation. On the other hand, more significant increases in net charges, such as in P3K-G11K-Temporin F, result in a severe increase in toxicity with lower gains in antimicrobial activity (TW of 0.65). In conclusion, we demonstrated that a moderate increase in net charge can lead to a more active analog and G6K-Temporin F is revealed to be promising as a candidate for new AMP therapeutics.

Intragenic antimicrobial peptide Hs02 toxicity against leukemia cell lines is associated with increased expression of select pyroptotic components

The anticancer potential of some antimicrobial peptides has been reported. Hs02 is a recently characterized Intragenic Antimicrobial Peptide (IAP), which was able to exhibit potent antimicrobial and anti-inflammatory action. In this study, we evaluate for the first time the antineoplastic potential of the Hs02 IAP using cell lines representing the main types of leukemia as cancer models. Interestingly, this peptide decreased the viability of several leukemic cell lines, without compromising the viability of PBMCs in the same concentration. In the HL-60 line, treatment with Hs02 controlled cell division, leading to cell arrest in the G1 phase of the cell cycle. More importantly, HL-60 cells treated with Hs02 undergo cell death, with the formation of pores in the plasma membrane and the release of LDH. Accordingly, Hs02 treatment stimulated the expression of components involved in pyroptosis, such as NLRP1, CASP-1, GSDME, and IL-1β. Taken together, our data characterize the antineoplastic potential of Hs02 and open an opportunity for both evaluating the peptide's antineoplastic potential in other cancer models and using this molecule as a template for new peptides with therapeutic potential against cancer.

Antimicrobial activity, toxicity and retrospective clinical effectiveness of Kantinka BA and Kantinka Herbaltics, two multi-component-herbal products used in the management of infectious diseases in Ghana

There is an upsurge in the incidence of persons living with infectious diseases and their associated symptoms. Also, there is increased resistance and high cost of available synthetic antimicrobial therapeutic agents. This calls for screening candidate herbal products to examine the risk-to-benefit ratio for users. Moreover, there are inadequate proven scientific studies to assess the quality, effectiveness, and toxicity of herbal products that traditional medicine practitioners in Ghana commonly use for the management of infectious diseases such as those caused by Neisseria gonorrhoeae, Candida albicans and the symptomatic management of symptoms associated with infections like cough, skin infections among others and gastritis. Kantinka BA and Kantinka Herbaltics, two multicomponent herbal products, have been used to manage the above-mentioned disease conditions. The study aims to evaluate the in vitro antibacterial activity, assess the retrospective clinical effectiveness (clinical responses; the disappearance of presenting signs and symptoms associated with infections, gastritis), and the quality and toxicity of Kantinka BA and Kantinka Herbaltics. The products are registered by the Food and Drugs Authority (FDA). Data on 200 patients who were diagnosed with infectious diseases such as Human Immunodeficiency Virus (HIV) / Acquired Immunodeficiency Syndrome (AIDS) and associated symptoms from January 2018 to June 2018 was obtained from the Adom Herbal Clinic, and the Tafo Government Herbal Medicine Records Unit was assessed. The antibacterial activity of the products was evaluated using the HT-SPOTi method. Phytochemical screening, microbial load, and pH were carried out according to standard procedures. Acute toxicity was carried out according to the Organization for Economic Cooperation and Development (OECD) guideline 425. Phytochemical screening, pH, and microbial load have been established for both products. Binding toxicity studies revealed that the products are non-toxic at a 2000 mg/kg dose. The two products exhibited antimicrobial activities against the test organisms with Minimum Inhibitory Concentration (MIC) and Minimum Lethal Concentration (MLC) determined for Kantinka BA and Kantinka Herbaltics as 5% and 10% and <80, respectively, against C. albicans and N. gonorrhoeae - the signs and symptoms associated with infections disappeared during the management period. The products are safe and may effectively manage some infectious diseases and associated symptoms.

Exploring Carbon Nanotubes as Antimicrobial Agents: Efficacy, Toxicity, Challenges, and Future Prospects

Carbon nanotubes (CNTs), including single-walled carbon nanotubes (SWNTs), have been integrated into pharmaceutical and medical domains as drug delivery systems since the turn of the twenty-first century. Their capacity to effectively transport diverse therapeutics across membranes and into living cells has sparked interest in medicinal applications encompassing enhanced imaging, antimicrobial solutions, tissue regeneration, and targeted medication or gene delivery. Amidst the wealth of evidence showcasing the advantages of CNTs, such as heightened efficacy and reduced side effects, recent studies have unveiled unforeseen toxicities linked to their usage. Notably, the antimicrobial potential of CNTs has garnered significant attention, promising novel strategies for combating microbial infections. This mini review presents a synthesis and discussion of both the antimicrobial attributes and potential toxicity associated with carbon nanotubes. Despite their promising potential, several challenges stand as important considerations, deciphering the precise mechanisms through which CNTs exert their antibacterial effects remains a complex puzzle and ensuring the biocompatibility and safety of CNTs, both in terms of host cells and the environment, is paramount for clinical translation. Lastly, navigating regulatory pathways and standardization efforts will be integral for realizing the scope of CNTs as antimicrobial agents. The multifaceted nature of CNTs' antibacterial attributes underscores the complexity of their interactions within various systems. Addressing challenges through surface functionalization to enhance hydrophilicity and biocompatibility underscores a strategic approach for future exploration. As research progresses, carbon nanotubes hold the potential to emerge as a pivotal tool in the fight against microbial infections while offering innovative pathways for therapeutic advancements.

Sequential Reductive Dechlorination of Triclosan by Sediment Microbiota Harboring Organohalide-Respiring Dehalococcoidia.

Aquatic ecosystems represent a prominent reservoir of xenobiotic compounds, including triclosan (TCS), a broad-spectrum biocide extensively used in pharmaceuticals and personal care products. As a biogeochemical hotspot, the potential of aquatic sediments for the degradation of TCS remains largely unexplored. Here, we demonstrated anaerobic biotransformation of TCS in a batch microcosm established with freshwater sediment. The initial 43.4 ± 2.2 μM TCS was completely dechlorinated to diclosan, followed by subsequent conversion to 5-chloro-2-phenoxyphenol, a monochlorinated TCS (MCS) congener. Analyses of community profile and population dynamics revealed substrate-specific, temporal-growth of Dehalococcoides and Dehalogenimonas, which are organohalide-respiring bacteria (OHRB) affiliated with class Dehalococcoidia. Dehalococcoides growth was linked to the formation of diclosan but not MCS, yielding 3.6 ± 0.4 × 107 cells per μmol chloride released. A significant increase in Dehalogenimonas cells, from 1.5 ± 0.4 × 104 to 1.5 ± 0.3 × 106 mL-1, only occurred during the reductive dechlorination of diclosan to MCS. Dehalococcoidia OHRB gradually disappeared following consecutive transfers, likely due to the removal of sediment materials with strong adsorption capacity that could alleviate TCS's antimicrobial toxicity. Consequently, a solid-free, functionally stable TCS-dechlorinating consortium was not obtained. Our results provide insights into the microbial determinants controlling the environmental fate of TCS.

Molecular Docking, Acute Toxicity and Antibacterial Study of Debilon and Phorbasterone-B Extracted from Rhodophyta

Introduction: Natural compounds obtained from marine algae, especially Rhodophyta are now being investigated for various biological activities. However, the antimicrobial activity and toxicity profile of compounds present in these algae isunderexplored. Objective: This study procured two compounds, Debilon and Phorbasterone-B, from Rhodophyta to analyze their in silico and in vitro potential against pathogenic bacterial strains and their acute toxicity. Methods: Debilon and Phorbasterone-B were extracted from Rhodophyta by a previously reported method and were further subsequently exploited computationally for their physicochemical properties, prediction of biological activity and molecular docking against bacterial proteins, toxicity, and experimentally for antibacterial potential against pathogenic strains of Vibrio cholera, Salmonella typhi, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Results: Docking studies proved that these molecules possess a chemical affinity for the bacterial proteins and can inhibit the growth of these microorganisms, as confirmed by antibacterial assay. Whereas the prediction analysis and toxicity studies showed that the friendliness of these molecules to the human body is enormous. Conclusion: From this study, it has been proved that DN and PB are perfect candidates for inhibiting these bacterial strains.

In vivo assessment of antimicrobial activity and toxicity of repeated 1% povidone-iodine applications vs a single 5% povidone-iodine application.

To demonstrate the noninferiority in antimicrobial effectiveness of thrice-repeated applications of 1% povidone-iodine (PI) compared with a single application of 5% PI on the ocular surface in vivo and to evaluate potential toxicity of PI to the corneal epithelium. Department of Ophthalmology, Shaare Zedek Medical Center, Jerusalem, Israel. Prospective, randomized, double-blind study. Patients randomly received either a single application of 5% PI or repeated irrigations of 1% PI on the ocular surface preoperatively. Bacterial colony counts were quantitatively analyzed by taking standardized conjunctival swabs before and after irrigation, and differences in bacterial colony counts were compared between the 2 groups. The presence of superficial punctate keratopathy was evaluated in all patients by the National Eye Institute grading system. The study comprised 102 eyes of 102 patients. Both 1% and 5% PI yielded a marked decrease in bacterial colonies compared with before application ( P < .001). The repeated application of 1% PI showed a significantly lower bacterial count compared with the single application of 5% PI ( P < .05) and resulted in significantly less damage to the corneal epithelium compared with a single 5% PI application ( P < .001). Preoperative repeated applications of 1% PI effectively eradicated ocular surface bacteria equal to that of 5% PI with a less deleterious effect on the corneal epithelium. Our findings suggest that 1% PI may be a promising alternative to 5% PI.

Phyto chemical screening,formulation of cream and it’s antifungal activity of stem extract from panikoorka plant

The panikoorka plant is a noble plant which is packed with various benefits, belonging to the family Lamiaceae as it may help in lowering blood sugar levels, maintaining heart health, and helps in digestive system, the stem of panikoorka is also having the anti-cancer activity some studies also prove that the extract of panikoorka stem are effective against the acne causing bacteria (anti-microbial).We are formulating the anti-fungal cream with the extract of panikoorka stem, we have collected the different extracts of the panikoorka stem, we have formulated 2 different formulations with the stem of panikoorka (Plectranthus barbatus).The Plant extract is used to treat different types of infectious disease, hence microbial screening attempted to prove its anti-bacterial and anti-fungal activity. The demonstration of therapeutic efficacy was achieved through the use of defined settings to restrict microbial development.The paper disc diffusion method was employed in this work to assess the synthetic compounds' in vitro antifungal efficacy. One technique for figuring out the relative efficacy of the anti-fungal activity is the paper disc diffusion method. The anti-microbial drugs' toxicity and their capacity to permeate into the medium both affect the outcomes of this approach. Although it is not as effective as standard, our produced cream has antifungal action against both Aspergillus niger and Candida albicans bacteria.

How mineral induced antibiotic transformation products impact bacterial growth and denitrification activity.

The abiotic transformations of quinolones and tetracyclines facilitated by redox-active minerals has been studied extensively, however limited information is available regarding the antimicrobial activity and toxicity of their resultant transformation products. In this study, we first investigated the mechanisms underlying the transformation of two commonly used antibiotics, ciprofloxacin (CIP) and tetracycline (TC), by the ubiquitous redox soil mineral, birnessite (MnO2). Subsequently, we evaluated the impact of these transformation products on both the growth and activity of the environmental denitrifier Pseudomonas veronii. Following the reaction with birnessite, four transformation products for CIP and five for TC were identified. Remarkably, the antibacterial activity of both CIP and TC was lost upon the formation of transformation products during their interaction with birnessite. This loss of antimicrobial efficacy was associated with specific chemical transformations, such as the opening of the piperazine ring for CIP and hydroxylation and demethylation for TC. Interestingly, denitrifying activity, quantified in terms of nitrate reduction rates, remained unaffected by both CIP and TC at low concentrations that did not impact bacterial growth. However, under certain conditions, specifically at low concentrations of CIP, the second step of denitrification-nitrite reduction-was hindered, leading to the accumulation of nitrite. Our findings highlight that the transformation products induced by the mineral-mediated reactions of CIP or TC lose the initial antibacterial activity observed in the parent compounds. This research contributes valuable insights into the intricate interplay between antibiotics, redox-active minerals, and microbial activity in environmental systems.

Revealing molecular dynamics of nanoparticles' antimicrobial activity, toxicities and coping up strategies

There is a growing interest in nanoformulations of medicinal drugs for antibacterial, antiviral, antifungal, antiprastic, and antioxidant drug delivery applications by researchers. Using nanoformulations, the conventional medicines have enhanced their functional properties and are more targeted to specific distribution sites. Some Nanoformulations gaining prominence in the pharmaceutical industry are hydrogels, nanocrystals, polymeric nanoparticles, liposomes, nanoemulsions, and micelles. The metal nanoparticles (silver, gold, iron oxide, and others) and nanoemulsions cause protein and DNA damage, producinge ROS (reactive oxygen species) as salient antimicrobial tools. Nanomaterials have been utilized in biomedical applications, spanning metals, nonmetallic/inorganic materials, and biodegradable materials. Human cells exhibit toxicity (e.g.Titanium dioxide) towards nanoparticles (NPs) due to the presence of synthetic chemicals as surface functional agents. Consequently, the nanoparticles alone can induce hepatotoxicity, skin sensitization, and damage. A focus on strategies such as coupling agents has been used in recent advancements aimed at reducing the toxicity of nanoformulations. These modified nanostructures provide safer and more efficient biomedical applications by reducing toxicity and enhancing antimicrobial activity.

Evaluation of the Antimicrobial Activity and Toxicity of Local and Foreign Seeds of Azanza Garckeana (Goron Tula) Extracts

Drug resistance poses a challenge to antimicrobial treatment options necessitating the continuous search of plant extracts with therapeutic potentials. The study determines the antimicrobial activities and toxicity effect of local and foreign seeds of Azanza garckeana. Constituents of the seeds of A. garckeana were extracted and identified using standard phytochemical procedures. Clinical isolates from patients diagnosed with Urinary Tract Infections (UTIs) were confirmed using standard microbiological procedures. Disk diffusion techniques were used to assess the antimicrobial properties of the plant extract, and Mass Spectrometry and Gas Chromatography were used to identify the bioactive components. Toxicity of plant extract was assessed using acute toxicity test, histopathological and hematological studies. The findings indicated the existence of alkaloids, carbohydrates, saponins, tannins and flavonoids in both local and foreign seeds of A. garckeana. Five (5) organisms were identified from patient with UTIs. Antimicrobial activities showed that the Petroleum ether extract of foreign A. garckeana exhibited higher antibacterial activity against Staphylococcus aureus (15mm), Pseudomonas aeruginosa (13mm) than Petroleum ether extract of local A. garckeana at a concentration of 200µg/ml respectively. Similarly, A. garckeana foreign aqueous extracts showed higher activity against S. aureus (13mm), and P. aeruginosa (12mm) than local Aqueous A. garckeana at a concentration of 200µg/ml respectively. The GCMS analysis showed the existence of Dodecanoic acid, ethyl ester, Octadecenoic acid, Undecanoic acid and methyl ether. Both the local and foreign seeds of A. garckeana were found to be non-toxic at ≤ 600 mg/kg. Histopathological and hematological studies showed heart with normal features, kidney with slight hyperplasia of inflammatory cells and liver with slight hepatic necrosis at 1000 mg/kg. The study demonstrated that the local and foreign seeds of Azanza garckeana had antimicrobial therapeutic potential but its usage should be dose dependent not exceeding ≤ 600 mg/kg.

Biomimetic protein structural transitions regulate activation and inhibition of the broad-spectrum bactericidal activity of cationic nanoparticles

The development of cationic polymers as alternative materials to antibiotics necessitates addressing the challenge of balancing their antimicrobial activity and toxicity. Here we propose a precise switching strategy inspired by biomimetic voltage-gated ion channels, enabling controlled activation and inhibition of cationic antimicrobial functions through protein conformational transitions in diverse physiological environments. Following thermodynamic studies on the specific recognition between mannose end groups on polycations and concanavalin A (ConA), we synthesized a type of ConA-polycation nanoparticle. The nanoparticle was inhibited under neutral conditions, with cationic moieties shielded by ConA's β-sheet. This shielding suppresses their antimicrobial activity, thereby ensuring satisfactory biocompatibility. In mildly acidic environments, however, the transition of a portion of ConA to an α-helix conformation exposed cations at the particle periphery, activating antibacterial functionality. Compared to inhibited nanoparticles, those in the activated state exhibited a 32–256 times reduction in the minimum bactericidal concentration against bacteria and fungi (2–16 µg/mL). In a murine acute pulmonary infection model, intravenous administration of inhibited nanoparticles effectively reduced bacterial counts by 4-log within 12 h. The biomimetic design, regulating cationic antimicrobial functionality through the alteration in protein secondary structure, significantly retards bacterial resistance development, holding great promise for intelligent antimicrobial materials. Statement of significanceCationic antimicrobial polymers exhibit advantages distinct from antibiotics due to their lower propensity for resistance development. However, the presence of cationic moieties also poses a threat to healthy cells and tissues, significantly constraining their potential for clinical applications. To address this challenge, we propose a biomimetic strategy that mimics voltage-gated ion channels to activate the antimicrobial functionality of cations selectively in bacterial environments through the conformational transitions of proteins between β–sheets and α–helices. In healthy tissues, the antimicrobial functionality is inhibited, ensuring satisfactory biocompatibility. Antimicrobial cationic materials capable of intelligent switching between an activated state and an inhibited state in response to environmental changes offer an effective strategy to prevent the development of resistance and mitigate potential side effects.

Peptide-rich extracts from leaves of &lt;i&gt;Newbouldia laevis&lt;/i&gt; (P. Beauv.) Seem. ex. Bureau (Bignoniaceae) with antimicrobial and brine shrimp lethality activities

Global concerns over antibiotic-resistant microbial pathogens have spurred a quest for innovative, stable, and target-specific molecules like bioactive peptides. This study evaluates the antimicrobial properties and toxicity of peptide-enriched extracts from Newbouldia laevis leaves. Aqueous extraction, thin layer chromatography (TLC), and Phenomenex's Stratum Giant Tube C18-E were used to obtain partly purified fraction (PPF) and crude peptide extracts (CPE). Antimicrobial inhibitory capacity was determined using p-INT dye, with gentamicin and fluconazole as standards. Cytotoxicity was assessed with Artemia salina nauplii. Microsoft Excel and GraphPad Prism 5 was used in analysing the data. Peptides were detected in CPE and PPF via TLC and modified G-250. PPF demonstrated more efficacy (IC50: 5.89μg/mL to 33.94μg/mL) against bacteria and fungi, with low toxicity (LC50: 5964.87μg/mL for PPFand 1094.20μg/mL for CPE) in the Brine shrimp lethality assay. The study presents the discovery of bioactive peptides from the leaves of Newbouldia laevis. Consequently, bioactive peptides extracted from this plant hold potential as foundational compounds for the development of novel broad-spectrum antibiotics aimed at combating microbial infections.

Whole genome case-control study of central nervous system toxicity due to antimicrobial drugs.

A genetic predisposition to central nervous system (CNS) toxicity induced by antimicrobial drugs (antibiotics, antivirals, antifungals, and antiparasitic drugs) has been suspected. Whole genome sequencing of 66 cases and 833 controls was performed to investigate whether antimicrobial drug-induced CNS toxicity was associated with genetic variation. The primary objective was to test whether antimicrobial-induced CNS toxicity was associated with seventeen efflux transporters at the blood-brain barrier. In this study, variants or structural elements in efflux transporters were not significantly associated with CNS toxicity. Secondary objectives were to test whether antimicrobial-induced CNS toxicity was associated with genes over the whole genome, with HLA, or with structural genetic variation. Uncommon variants in and close to three genes were significantly associated with CNS toxicity according to a sequence kernel association test combined with an optimal unified test (SKAT-O). These genes were LCP1 (q = 0.013), RETSAT (q = 0.013) and SFMBT2 (q = 0.035). Two variants were driving the LCP1 association: rs6561297 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]) and the regulatory variant rs10492451 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]). No common genetic variant, HLA-type or structural variation was associated with CNS toxicity. In conclusion, CNS toxicity due to antimicrobial drugs was associated with uncommon variants in LCP1, RETSAT and SFMBT2.

Mycogenic silver nanoparticles from Penicillium citrinum IB-CLP11 – their antimicrobial activity and potential toxicity effects on freshwater organisms

Silver nanoparticles (AgNPs) are some of the most attractive nanomaterials for commercial applications, but they can also be a very challenging issue from the point of view of cytotoxicity and phytotoxicity as agents that damage genetic information.

Can large language models predict antimicrobial peptide activity and toxicity?

Antimicrobial peptides (AMPs) are naturally occurring or designed peptides up to a few tens of amino acids which may help address the antimicrobial resistance crisis. However, their clinical development is limited by toxicity to human cells, a parameter which is very difficult to control. Given the similarity between peptide sequences and words, large language models (LLMs) might be able to predict AMP activity and toxicity. To test this hypothesis, we fine-tuned LLMs using data from the Database of Antimicrobial Activity and Structure of Peptides (DBAASP). GPT-3 performed well but not reproducibly for activity prediction and hemolysis, taken as a proxy for toxicity. The later GPT-3.5 performed more poorly and was surpassed by recurrent neural networks (RNN) trained on sequence-activity data or support vector machines (SVM) trained on MAP4C molecular fingerprint-activity data. These simpler models are therefore recommended, although the rapid evolution of LLMs warrants future re-evaluation of their prediction abilities.