Antibiotic Resistance Crisis Research Articles

Phytochemical analysis and evaluation of the antibacterial and antibiotic potentiation activities of the aqueous extract of Cordia oncocalyx Allemão (Boraginaceae)

The global antibiotic resistance crisis highlights the inappropriate use of medicines by the population and the lack of development of new antimicrobial agents. According to various studies, natural products are promising alternatives for combating bacterial resistance and treating infectious diseases. Accordingly, the present study aimed to analyze the chemical composition and evaluate the antibacterial and antibiotic potential of an aqueous extract of Cordia oncocalyx Allemão (AECO). Phytochemical analyses were performed using high-performance liquid chromatography equipped with a diode array detector (HPLC-DAD). The minimum inhibitory concentration (MIC) was used to evaluate the antibacterial activity of C. oncocalyx against conventional and multidrug-resistant (MDR) bacterial strains (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). According to HPLC-DAD analysis, the following compounds could be identified in the aqueous extract of C. oncocalyx: luteolin (3.07 ± 0.04 mg/g), caffeic acid (1.05 ± 0.03 mg/g), ellagic acid (0.62 ± 0.05 mg/g), and quercetin (0.58 ± 0.01). AECO did not exhibit antibacterial activity when administered alone (MIC >512 μg/mL). However, when combined with gentamicin, ampicillin, and norfloxacin, AECO potentiated the action of these antibiotics against the multi-resistant strains of P. aeruginosa and S. aureus. Although clinical relevance was not revealed by the in vitro tests against pathogenic bacteria, AECO can combined with commercial antibiotics to improve their antibacterial effects. Future studies focusing on the mechanisms of action of the compounds isolated from C. oncocalyx and toxicological tests are fundamental.

Antibody-Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections.

Antibodies are significant agents in the immune system and have proven to be effective in treating bacterial infections. With the advancement of antibody engineering in recent decades, antibody therapy has evolved widely. This review aimed to investigate a new method as a therapeutic platform for the treatment of bacterial infections and explore the novel features of this method in conferring pathogen specificity to broad-spectrum antibiotics. A literature review was conducted addressing the following topics about antibody-antibiotic conjugates (AACs): (1) structure and mechanism of action; (2) clinical effectiveness; (3) advantages and disadvantages. Antibody conjugates are designed to build upon the progress made in the development of monoclonal antibodies for the treatment of diseases. Despite the growing emergence of antibiotic resistance among pathogenic bacteria worldwide, novel antimicrobials have not been sufficiently expanded to combat the global crisis of antibiotic resistance. A recently developed strategy for the treatment of infectious diseases is the use of AACs, which are specifically activated only in host cells. A novel therapeutic AAC employs an antibody to deliver the antibiotic to the bacteria. The AACs can release potent antibacterial components that unconjugated forms may not exhibit with an appropriate therapeutic index. This review highlights how this science has guided the design principles of an impressive AAC and discusses how the AAC model promises to enhance the antibiotic effect against bacterial infections.

Antibacterial and antibiotics resistance modifying activity of oil extract of Myristica fragrans’s mace (aril) against Multi-Antibiotic Resistant phenotypes with a comparative study against Cymbopogon citratus

This study systematically inspects the potent antimicrobial properties inherent in Myristica fragrance (Javitri) and Cymbopogon citratus (Lemongrass) essential oils. The core point is the targeted action against multiantibiotic-resistant (MAR) bacteria, a critical concern amidst the rising tide of antibiotic resistance. Notably, herbal alternatives are gaining traction as promising solutions. The research involves methodical extraction and assessment of these oils against formidable MAR strains, involving Escherichia coli and Pseudomonas sp. and through GC-MS analysis, we were able to find out the phytochemicals responsible for outstanding antimicrobial property of essential oil extracted from the mace of Myristica fragrans(Javitri). A significant part of this investigation delves into the synergistic interplay of Myristica fragrans oil with antibiotics. Through our research, we intend to re-establish the application of traditional herbal components for the purpose of medication and also in synergism with ineffective antibiotics and therapeutic strategies to face the antibiotic resistance crisis.

Ensuring a sustained workforce to combat antibiotic resistance in the 21st century: the critical need for training the next-gen of scientists at the pre-doctoral level.

Antibiotics revolutionized the treatment of bacterial infection and enhanced modern healthcare. While the current global antibiotic resistance crisis is widely acknowledged, the need for a highly trained cohort of scientists to continue and expand efforts to combat this threat has received less attention. We posit that training of pre-doctoral students in the antibiotic resistance field is critical for future efforts in combating this crisis and urge development of training programs that focus on this need.

Combating Multidrug Resistance: The Potential of Antimicrobial Peptides and Biofilm Challenges

The escalating crisis of antibiotic resistance represents a formidable challenge to global public health, necessitating urgent and innovative solutions. This review delves into the multifaceted nature of antibiotic resistance, emphasizing the pivotal role of biofilms and the genetic mechanisms underpinning resistance in both Gram-positive and Gram-negative bacteria. A significant focus is placed on Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), and its mechanisms of resistance, including the SCCmec element and the agr quorum sensing system. The review also explores the alarming rise of resistance in Gram-negative pathogens, such as E. coli and K. pneumoniae, highlighting the perilous spread of extended-spectrum β- lactamases (ESBLs) and carbapenemases. Amidst this dire landscape, antimicrobial peptides (AMPs), particularly melittin from bee venom (BV), emerge as promising agents capable of breaching microbial defenses, including those of dormant cells within biofilms, thus offering a potential strategy to circumvent traditional resistance mechanisms. The review underscores the necessity of understanding bacterial survival strategies, such as biofilm formation and genetic adaptation, to develop effective countermeasures against antibiotic-resistant infections.

Comparison of methods proposed for monitoring cefotaxime-resistant Escherichia coli in the water environment.

Escherichia coli is a promising subject for globally coordinated surveillance of antimicrobial resistance (AMR) in water environments due to its clinical relevance and widespread use as an indicator of fecal contamination. Cefotaxime-resistant E. coli was recently evaluated favorably for this purpose by the World Health Organization TriCycle Protocol, which specifies tryptone bile x-glucuronide (TBX) medium and incubation at 35°C. We assessed comparability with the U.S. Environmental Protection Agency-approved method for E. coli quantification, which uses membrane-thermotolerant E. coli (mTEC) agar and incubation at 44.5°C, in terms of recovery of E. coli and cefotaxime-resistant E. coli from wastewater influent and surface waters. Total E. coli concentrations in wastewater influent were 106-108 CFU/100 mL, while cefotaxime-resistant E. coli were ~100-fold lower. Total E. coli in surface waters were ~102 CFU/100 mL, and cefotaxime-resistant isolates were near the limit of detection (0.4 CFU/100 mL). Total and putative cefotaxime-resistant E. coli concentrations did not differ significantly between media or by incubation method; however, colonies isolated on mTEC were more frequently confirmed to species (97.1%) compared to those from TBX (92.5%). Incubation in a water bath at 44.5°C significantly decreased non-specific background growth and improved confirmation frequency on both media (97.4%) compared to incubation at 35°C (92.3%). This study helps to advance globally coordinated AMR in water environments and suggests that the TriCycle Protocol is adaptable to other standard methods that may be required in different locales, while also offering a means to improve specificity by decreasing the frequency of false-positive identification of cefotaxime-resistant E. coli by modifying incubation conditions.IMPORTANCEAs antibiotic-resistant bacteria in water environments are increasingly recognized as contributors to the global antibiotic resistance crisis, the need for a monitoring subject that captures antibiotic resistance trends on a global scale increases. The World Health Organization TriCycle Protocol proposes the use of cefotaxime-resistant Escherichia coli isolated on tryptone bile x-glucuronide agar. The U.S. Environmental Protection Agency (USEPA) criteria for safe recreational waters also use E. coli as an indicator but specify the use of mTEC agar at a higher incubation temperature (44.5°C vs 35°C). We assessed the comparability of these methods for isolating total and cefotaxime-resistant E. coli, finding overall good agreement and performance, but significantly higher specificity toward E. coli selection with the use of the USEPA incubation protocol and mTEC agar. This study is the first to directly compare these methods and provides evidence that the methods may be used interchangeably for global surveillance of antibiotic resistance in the environment.

Causal-ARG: a causality-guided framework for annotating properties of antibiotic resistance genes.

The crisis of antibiotic resistance, which causes antibiotics used to treat bacterial infections to become less effective, has emerged as one of the foremost challenges to public health. Identifying the properties of antibiotic resistance genes (ARGs) is an essential way to mitigate this issue. Although numerous methods have been proposed for this task, most of these approaches concentrate solely on predicting antibiotic class, disregarding other important properties of ARGs. In addition, existing methods for simultaneously predicting multiple properties of ARGs fail to account for the causal relationships among these properties, limiting the predictive performance. In this study, we propose a causality-guided framework for annotating properties of ARGs, in which causal inference is utilized for representation learning. More specifically, the hidden biological patterns determining the properties of ARGs are described by a Gaussian Mixture Model, and procedure of causal representation learning is used to derive the hidden features. In addition, a causal graph among different properties is constructed to capture the causal relationships among properties of ARGs, which is integrated into the task of annotating properties of ARGs. The experimental results on a real-world dataset demonstrate the effectiveness of the proposed framework on the task of annotating properties of ARGs. The data and source codes are available in GitHub at https://github.com/David-WZhao/CausalARG.

Restoration of Antibacterial Activity of Inactive Antibiotics via Combined Treatment with AgNPs.

Antimicrobial resistance poses a huge threat to human health around the world and calls for novel treatments. Combined formulations of NPs and antibiotics have emerged as a viable nanoplatform for combating bacterial resistance. The present research work was performed to investigate the effect of combined formulations of AgNPs with streptomycin, cefaclor, ciprofloxacin, and trimethoprim against multidrug-resistant (MDR) isolates of Staphylococcus aureus and Klebsiella pneumoniae. AgNPs have been synthesized by using the Nigella sativa seed extract, and their characteristics were analyzed. AgNPs depicted concentration-dependent antibacterial effects, as the highest concentration of AgNPs showed the strongest antibacterial activity. Interestingly, AgNPs in conjugation with antibiotics showed an enhanced antibacterial potential against both S. aureus and K. pneumoniae, which suggested synergism between the AgNPs and antibiotics. Against S. aureus, streptomycin and trimethoprim in conjugation with AgNPs presented a synergistic effect, while cefaclor and ciprofloxacin in combination with AgNPs showed an additive effect. However, all of the tested antibiotics depicted a synergistic effect against K. pneumoniae. The lowest value of MIC (0.78 μg/mL) was shown by AgNPs-Stp against S. aureus, whereas AgNPs-Tmp showed the lowest value of MIC (1.56 μg/mL) against K. pneumoniae. The most important point of the present study is that both organisms (S. aureus and K. pneumoniae) showed resistance to antibiotics but turned out to be highly susceptible when the same antibiotic was used in combination with AgNPs. These findings highlight the potential of nanoconjugates (the AgNPs-antibiotic complex) to mitigate the present-day crisis of antibiotic resistance and to combat antimicrobial infections efficiently.

Bacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model

One of the hopes for overcoming the antibiotic resistance crisis is the use of bacteriophages to combat bacterial infections, the so-called phage therapy. This therapeutic approach is generally believed to be safe for humans and animals as phages should infect only prokaryotic cells. Nevertheless, recent studies suggested that bacteriophages might be recognized by eukaryotic cells, inducing specific cellular responses. Here we show that in chickens infected with Salmonella enterica and treated with a phage cocktail, bacteriophages are initially recognized by animal cells as viruses, however, the cGAS-STING pathway (one of two major pathways of the innate antiviral response) is blocked at the stage of the IRF3 transcription factor phosphorylation. This inhibition is due to the inability of RNA polymerase III to recognize phage DNA and to produce dsRNA molecules which are necessary to stimulate a large protein complex indispensable for IRF3 phosphorylation, indicating the mechanism of the antiviral response impairment.

Phylogenomic and phenotypic analyses highlight the diversity of antibiotic resistance and virulence in both human and non-human Acinetobacter baumannii.

Acinetobacter baumannii is a Gram-negative, opportunistic pathogen that causes infections in the immunocompromised. With a high incidence of muti-drug resistance, carbapenem-resistant A. baumannii is designated as a priority 1 pathogen by the WHO. The current literature has expertly characterized clinical isolates of A. baumannii. As the challenge of these infections has recently been classified as a One Health issue, we set out to explore the diversity of isolates from human and non-clinical sources, such as agricultural surface water, urban streams, various effluents from wastewater treatment plants, and food (tank milk); and, importantly, these isolates came from a wide geographic distribution. Phylogenomic analysis considering almost 200 isolates showed that our diverse set is well-differentiated from the main international clones of A. baumannii. We discovered novel sequence types in both hospital and non-clinical settings and five strains that overexpress the resistance-nodulation-division efflux pump adeIJK without changes in susceptibility reflected by this overexpression. Furthermore, we detected a bla ADC-79 in a non-human isolate despite its sensitivity to all antibiotics. There was no significant differentiation between the virulence profiles of clinical and non-clinical isolates in the Galleria mellonella insect model of virulence, suggesting that virulence is neither dependent on geographic origin nor isolation source. The detection of antibiotic resistance and virulence genes in non-human strains suggests that these isolates may act as a genetic reservoir for clinical strains. This endorses the notion that in order to combat multi-drug-resistant infection caused by A. baumannii, a One Health approach is required, and a deeper understanding of non-clinical strains must be achieved.IMPORTANCEThe global crisis of antibiotic resistance is a silent one. More and more bacteria are becoming resistant to all antibiotics available for treatment, leaving no options remaining. This includes Acinetobacter baumannii. This Gram-negative, opportunistic pathogen shows a high frequency of multi-drug resistance, and many strains are resistant to the last-resort drugs carbapenem and colistin. Research has focused on strains of clinical origin, but there is a knowledge gap regarding virulence traits, particularly how A. baumannii became the notorious pathogen of today. Antibiotic resistance and virulence genes have been detected in strains from animals and environmental locations such as grass and soil. As such, A. baumannii is a One Health concern, which includes the health of humans, animals, and the environment. Thus, in order to truly combat the antibiotic resistance crisis, we need to understand the antibiotic resistance and virulence gene reservoirs of this pathogen under the One Health continuum.

Novel β-Hairpin Antimicrobial Peptide Containing the β-Turn Sequence of -NG- and the Tryptophan Zippers Facilitate Self-Assembly into Nanofibers, Exhibiting Excellent Antimicrobial Performance.

Antimicrobial peptides (AMPs) have emerged as promising agents to combat the antibiotic resistance crisis due to their rapid bactericidal activity and low propensity for drug resistance. However, AMPs face challenges in terms of balancing enhanced antimicrobial efficacy with increased toxicity during modification processes. In this study, de novo d-type β-hairpin AMPs are designed. The conformational transformation of self-assembling peptide W-4 in the environment of the bacterial membrane and the erythrocyte membrane affected its antibacterial activity and hemolytic activity and finally showed a high antibacterial effect and low toxicity. Furthermore, W-4 displays remarkable stability, minimal occurrence of drug resistance, and synergistic effects when combined with antibiotics. The in vivo studies confirm its high safety and potent wound-healing properties at the sites infected by bacteria. This study substantiates that nanostructured AMPs possess enhanced biocompatibility. These advances reveal the superiority of self-assembled AMPs and contribute to the development of nanoantibacterial materials.

Supramolecular Switch for the Regulation of Antibacterial Efficacy of Near-Infrared Photosensitizer.

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria.

Quantifying the Dynamics of Bacterial Biofilm Formation on the Surface of Soft Contact Lens Materials Using Digital Holographic Tomography to Advance Biofilm Research.

The increase in bacterial resistance to antibiotics in recent years demands innovative strategies for the detection and combating of biofilms, which are notoriously resilient. Biofilms, particularly those on contact lenses, can lead to biofilm-related infections (e.g., conjunctivitis and keratitis), posing a significant risk to patients. Non-destructive and non-contact sensing techniques are essential in addressing this threat. Digital holographic tomography emerges as a promising solution. This allows for the 3D reconstruction of the refractive index distribution in biological samples, enabling label-free visualization and the quantitative analysis of biofilms. This tool provides insight into the dynamics of biofilm formation and maturation on the surface of transparent materials. Applying digital holographic tomography for biofilm examination has the potential to advance our ability to combat the antibiotic bacterial resistance crisis. A recent study focused on characterizing biofilm formation and maturation on six soft contact lens materials (three silicone hydrogels, three hydrogels), with a particular emphasis on Staphylococcus epidermis and Pseudomonas aeruginosa, both common culprits in ocular infections. The results revealed species- and time-dependent variations in the refractive indexes and volumes of biofilms, shedding light on cell dynamics, cell death, and contact lens material-related factors. The use of digital holographic tomography enables the quantitative analysis of biofilm dynamics, providing us with a better understanding and characterization of bacterial biofilms.

Study of an Enterococcus faecium strain isolated from an artisanal Mexican cheese, whole-genome sequencing, comparative genomics, and bacteriocin expression

Enterococci are ubiquitous microorganisms in almost all environments, from the soil we step on to the food we eat. They are frequently found in naturally fermented foods, contributing to ripening through protein, lipid, and sugar metabolism. On the other hand, these organisms are also leading the current antibiotic resistance crisis. In this study, we performed whole-genome sequencing and comparative genomics of an Enterococcus faecium strain isolated from an artisanal Mexican Cotija cheese, namely QD-2. We found clear genomic differences between commensal and pathogenic strains, particularly in their carbohydrate metabolic pathways, resistance to vancomycin and other antibiotics, bacteriocin production, and bacteriophage and CRISPR content. Furthermore, a bacteriocin transcription analysis performed by RT-qPCR revealed that, at the end of the log phase, besides enterocins A and X, two putative bacteriocins not reported previously are also transcribed as a bicistronic operon in E. faecium QD-2, and are expressed 1.5 times higher than enterocin A when cultured in MRS broth.

Enhanced phytoremediation of metal contaminated soils aimed at decreasing the risk of antibiotic resistance dissemination

The enhanced phytoremediation of metal contaminated soils holds great promise for the recovery of soil health and functionality, while providing a range of co-benefits, from an environmental and human health perspective, derived from the revegetation of the degraded sites and the concomitant delivery of ecosystem services. Due to diverse evolutionary co-selection mechanisms between metal resistance and antibiotic resistance in bacteria, metal contaminated soils are considered potential reservoirs of antibiotic resistant bacteria (ARB) which can contribute to the existing antibiotic resistance crisis. During the enhanced phytoremediation of metal contaminated soils, the application of organic wastes (e.g., manure, slurry, sewage sludge) as soil amendments can aggravate the risk of antibiotic resistance spread, because they often contain ARB which harbor antibiotic resistance genes (ARGs) that can then be propagated among soil bacterial populations through horizontal gene transfer (HGT). Due to the magnitude and criticality of the antibiotic resistance crisis, as well as the higher risk of spread and dispersal of ARB and ARGs (they make copies of themselves) compared to metals, it is proposed here to aim enhanced phytoremediation strategies towards decreasing the soil resistome (and, hence, the risk of its potential link with the human resistome), while reducing total and/or bioavailable metal concentrations and restoring soil health and the delivery of ecosystem services. To this purpose, a decalogue of practices is tentatively suggested. Finally, a proper management of plant and soil microbial compositions is a most crucial aspect, together with the selection of the right organic wastes and phytoremediation practices.

Ciprofloxacin Poly(β-amino ester) Conjugates Enhance Antibiofilm Activity and Slow the Development of Resistance.

To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial biofilms are a particular concern in this context as they are responsible for over 80% of bacterial infections and are inherently more recalcitrant toward antimicrobial treatments. The high tolerance of biofilms to conventional antibiotics has been attributed to several factors, including reduced drug diffusion through the dense exopolymeric matrix and the upregulation of antimicrobial resistance machinery with successful biofilm eradication requiring prolonged high doses of multidrug treatments. A promising approach to tackle bacterial infections involves the use of polymer drug conjugates, shown to improve upon free drug toxicity and bioavailability, enhance drug penetration through the thick biofilm matrix, and evade common resistance mechanisms. In the following study, we conjugated the antibiotic ciprofloxacin (CIP) to a small library of biodegradable and biocompatible poly(β-amino ester) (PBAE) polymers with varying central amine functionality. The suitability of the polymers as antibiotic conjugates was then verified in a series of assays including testing of efficacy and resistance response in planktonic Gram-positive and Gram-negative bacteria and the reduction of viability in mono- and multispecies biofilm models. The most active polymer within the prepared PBAE-CIP library was shown to achieve an over 2-fold increase in the reduction of biofilm viability in a Pseudomonas aeruginosa monospecies biofilm and superior elimination of all the species present within the multispecies biofilm model. Hence, we demonstrate that CIP conjugation to PBAEs can be employed to achieve improved antibiotic efficacy against clinically relevant biofilm models.

Design of a novel analogue peptide with potent antibiofilm activities against Staphylococcus aureus based upon a sapecin B-derived peptide

Nowadays, antimicrobial peptides are promising to confront the existing global crisis of antibiotic resistance. Here, a novel analogue peptide (mKLK) was designed based upon a D-form amidated sapecin B-derived peptide (KLK) by replacing two lysine residues with two tryptophan and one leucine by lysine, and inserting one alanine. The mKLK displayed superior amphipathic helixes in which the most of hydrophobic residues are confined to one face of the helix and had a higher hydrophobic moment compared with KLK. The mKLK retained its antibacterial activity and structure in human serum, suggesting its stability to proteolytic degradation. The values of MIC and MBC for mKLK were equal to those of KLK against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). However, mKLK showed more capability of in vitro inhibiting, eradicating, and dispersing MRSA and MSSA biofilms compared with KLK. Furthermore, a remarkable inhibitory activity of mKLK against MRSA and MSSA biofilms was seen in the murine model of catheter-associated biofilm infection. Results of this study show that mKLK not only exhibits antibacterial activity and serum stability but also a potent biofilm inhibitory activity at sub-MIC concentrations, confirming its potential therapeutic advantage for preventing biofilm-associated MRSA and MSSA infections.

Pandemic preparedness—political perspectives

Abstract Pandemic preparedness is explored for the antibiotic resistance crisis and the threat of a next viral pandemic. Bacterial pathogens escaping from control by antibiotics are well defined, and resistance develops over decades while a next viral pandemic occurs suddenly with a novel virus. The death toll for resistant bacterial infections is reviewed, and the scientific and economic hurdles to the development of new antibiotics are discussed. Regulatory adaptations and financial push and pull programs to restimulate new antibiotic development are explored. The COVID-19 pandemic caused not only millions of deaths, but also economic losses in excess of 10 trillion US dollars. Coronaviruses and influenza viruses remain usual suspects for new viral pandemics, followed by paramyxoviruses. Viral infections at the animal–human interface in wet markets and in disturbed environments need active virus surveillance programs. Learning lessons from the COVID-19 for non-pharmaceutical interventions is difficult to draw since measures were frequently applied in combination against different variant viruses and against changing population immunity levels. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) clinical trials demonstrated that even under emergency situations clinical trials can rapidly provide solid treatment data. Various novel vaccine approaches were the most efficient control measures for the COVID-19 pandemic. Pandemic preparedness also requires a fact-based discussion both in the public and in parliaments to settle the conflict between individual freedom and necessary restrictions during a pandemic. Mature and educated citizens are needed not only for coping with pandemics but also for creating stress-resistant democratic societies. Learned scientific societies should contribute to this discussion.

Development of cannabidiol derivatives as potent broad-spectrum antibacterial agents with membrane-disruptive mechanism

The emergence of antibiotic resistance has brought a significant burden to public health. Here, we designed and synthesized a series of cannabidiol derivatives by biomimicking the structure and function of cationic antibacterial peptides. This is the first report on the design of cannabidiol derivatives as broad-spectrum antibacterial agents. Through the structure-activity relationship (SAR) study, we found a lead compound 23 that killed both Gram-negative and Gram-positive bacteria via a membrane-targeting mechanism of action with low resistance frequencies. Compound 23 also exhibited very weak hemolytic activity, low toxicity toward mammalian cells, and rapid bactericidal properties. To further validate the membrane action mechanism of compound 23, we performed transcriptomic analysis using RNA-seq, which revealed that treatment with compound 23 altered many cell wall/membrane/envelope biogenesis-related genes in Gram-positive and Gram-negative bacteria. More importantly, compound 23 showed potent in vivo antibacterial efficacy in murine corneal infection models caused by Staphylococcus aureus or Pseudomonas aeruginosa. These findings would provide a new design idea for the discovery of novel broad-spectrum antibacterial agents to overcome the antibiotic resistance crisis.

Antibiotic action and resistance: updated review of mechanisms, spread, influencing factors, and alternative approaches for combating resistance.

Antibiotics represent a frequently employed therapeutic modality for the management of bacterial infections across diverse domains, including human health, agriculture, livestock breeding, and fish farming. The efficacy of antibiotics relies on four distinct mechanisms of action, which are discussed in detail in this review, along with accompanying diagrammatic illustrations. Despite their effectiveness, antibiotic resistance has emerged as a significant challenge to treating bacterial infections. Bacteria have developed defense mechanisms against antibiotics, rendering them ineffective. This review delves into the specific mechanisms that bacteria have developed to resist antibiotics, with the help of diagrammatic illustrations. Antibiotic resistance can spread among bacteria through various routes, resulting in previously susceptible bacteria becoming antibiotic-resistant. Multiple factors contribute to the worsening crisis of antibiotic resistance, including human misuse of antibiotics. This review also emphasizes alternative solutions proposed to mitigate the exacerbation of antibiotic resistance.