The minimum inhibitory concentration (MIC) assay is the gold standard for evaluating antimicrobial activity. However, conventional agar-based MIC methods often underestimate the potency of physicochemically complex compounds[1, 2]. Hydrophobic and adhesive molecules, such as lipoglycopeptide antibiotics, exhibit poor diffusion and non-specific binding to agar, leading to artificially elevated MIC values compared to broth-based methods[3]. This issue complicates accurate potency assessment, and is particularly an issue when attempting resistance frequency (FOR) studies, which must be conducted on solid media. Here, we developed a modified miniaturised agar MIC assay using 1% agarose, 0.002% Tween 80-supplemented tryptic soy broth (TSB), and a 24-well plate format[4]. These modifications improved compound dispersion, reduced matrix interactions, and lowered compound requirements. The optimised assay was validated with vancomycin, oritavancin, and dalbavancin against Staphylococcus aureus ATCC 43300 (MRSA) and Streptococcus pneumoniae ATCC 700677. This efficient, cost-effective, high-throughput platform overcomes the limitations of traditional agar methods, enhancing reliability in evaluating challenging antimicrobials and supporting next-generation antibiotic development.

Antimicrobial resistance (AMR) is the poster child for the need for a 'One Health' approach that develops solutions across the human, agricultural and environmental sectors. This article provides a viewpoint of where AMR research is heading in the future, from the perspective of three Australian initiatives specifically established to combat AMR: the Centre to Impact AMR, the ARC Training Centre for Environmental and Agricultural Solutions to Antimicrobial Resistance, and the Community for Open Antimicrobial Drug Discovery.

The increasing prevalence of paraben compounds in the environment has given rise to concerns regarding their detrimental impacts on both ecosystems and human health. Over the past few decades, photocatalytic reactions have drawn significant attention as a method to accelerate the otherwise slow degradation of these pollutants. The current study aims to evaluate the current efficacy of the photocatalytic method for degrading parabens in aqueous solutions. An extensive literature review and bibliometric analysis were conducted to identify key research trends and influential areas in the field of photocatalytic paraben degradation. Studies were screened based on the predetermined inclusion and exclusion criteria, which led to 13 studies that were identified as being appropriate for the meta-analysis using the random effects model. Furthermore, experimental parameters such as pH, paraben initial concentration, catalyst dosage, light intensity, and contact time have been reported to have key impacts on the performance of the photocatalytic degradation process. A comprehensive quantitative assessment of these parameters was carried out in this work. Overall, photocatalytic techniques could eliminate parabens with an average degradation efficiency of >80 %. The findings of the Egger's test and the Begg's test were statistically not significant suggesting potential publication bias was not observed. This review provides a holistic understanding of the photocatalytic degradation of parabens and is anticipated to encourage more widespread adoption of photocatalytic procedures as a suitable method for the elimination of parabens from aqueous solutions, opening new avenues for future research in this direction.

The rise of antimicrobial resistance has been accompanied by a decline in the development of new antibiotics. In this article, we explore the current state of affairs and trends in both human- and animal-related antibiotic development activity, with distinct differences between the two sectors.

Background: The increasing occurrence of MRSA clinical isolates harbouring reduced susceptibility to mainstay antibiotics has escalated the use of second and last line antibiotics. Hence, it is critical to evaluate the likelihood of MRSA developing clinical resistance to these antibiotics. Objectives: Our study sought to identify the rate in which MRSA develop resistance to vancomycin, daptomycin and linezolid in vitro and further determine the mechanisms underpinning resistance. Methods: MRSA was exposed to increasing concentrations of vancomycin, daptomycin, and linezolid for 20 days, with eight replicates for each antibiotic conducted in parallel. The resulting day 20 (D20) isolates were subjected to antimicrobial susceptibility testing, whole genome sequencing, autolysis assays, and growth curves to determine bacterial fitness. Results: Exposure to vancomycin or linezolid for 20 days resulted in a subtle two-fold increase in the MIC, whereas daptomycin exposure yielded daptomycin-nonsusceptible isolates with up to 16-fold MIC increase. The MIC increase was accompanied by variable changes in relative fitness and reduced resistance to autolysis in some isolates. D20 isolates harboured mutations in genes commonly associated with resistance to the respective antibiotics (e.g. walK for vancomycin, mprF and rpoB for daptomycin, rplC for linezolid), along with several previously unreported variants. Introduction of key mutations to these identified genes in the parental strain via allelic exchange confirmed their role in the development of resistance. Conclusions: In vitro selection against vancomycin, daptomycin, or linezolid resulted in the acquisition of mutations similar to those correlated with clinical resistance, including the associated phenotypic alterations. ### Competing Interest Statement M. A. C. currently holds a fractional Professorial Research Fellow appointment at the University of Queensland with his remaining time as CEO of Inflazome Ltd, a company with headquarters in Dublin, Ireland that is developing drugs to address clinical unmet needs in inflammatory disease by targeting the inflammasome.

Phenol is a well-known organic pollutant that poses a threat to environmental sustainability due to its prevalence in industrial effluents. This chemical is frequently found in industrial waste and can have detrimental effects on ecosystems. In order to address this issue, effective remediation strategies are essential. Carbon-based adsorbents have emerged as a popular solution in current research. These adsorbents have demonstrated exceptional efficiency in removing phenol from water, presenting a promising solution for phenol adsorption and promoting sustainable water management. The current study aims to evaluate the capacity of a novel hybrid aerogel synthesized from spent catalyst-generated carbon nanotubes (GO/CNTs) and graphene oxide (GO). The phenol adsorption efficiency and behavior of GO/CNTs were compared with three different carbon-based adsorbents: graphene oxide (GO), magnetic graphene oxide (MGO), and graphene oxide aerogel (GOA). The adsorption isotherm modeling of experimental data showed that GO/CNTs exhibited the highest phenol adsorption efficiency of 204 mg/g, followed by GOA (141 mg/g), according to the Langmuir isotherm model. The detailed adsorption mechanism was correlated with isotherm, kinetics, and thermodynamics datasets, and further validated by in-depth statistical analysis of models, confirming the superior phenol adsorption capacity of the wastederived hybrid aerogel. This research provides valuable insights into effective phenol removal from wastewater, emphasizing the promising performance of the novel GO/CNTs hybrid aerogel and providing optimized conditions for the adsorption process with statistical significance.

The coronavirus disease 2019 (COVID-19) pandemic led to a remarkably rapid development of a range of effective prophylactic vaccines, including new technologies that had not previously been approved for human use. In contrast, the development of new small molecule antiviral therapeutics has taken years to produce the first approved drugs specifically targeting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), with the intervening years filled with attempts to repurpose existing drugs and the development of biological therapeutics. This review will discuss the reasons behind this variation in timescale and provide a survey of the many new treatments that are progressing through the clinical pipeline.

Bacteremic Streptococcus pneumoniae pneumonia is one of the most severe forms of invasive pneumococcal disease (IPD) and with particularly high case-fatality rates among the elderly and individuals with comorbidities, exacerbated by rising antibiotic resistance and time to initiation of therapy. Here, we examined the efficacy of the preclinical "vancapticin" glycopeptide MCC5145 against fulminant infection by S. pneumoniae serotype 2 strain D39 in a bioluminescent, neutropenic mouse model of bacteremic pneumonia. MCC5145 is a semisynthetic vancomycin derivative chemically modified at the C-terminus with a membrane-targeting motif designed to preferentially bind the anionic bacterial surface. We show that similar to vancomycin, subcutaneous administration of MCC5145 to mice 1 day after intranasal infection with a bioluminescent derivative of S. pneumoniae D39 elicited time and concentration-dependent reduction in total flux in the lungs and blood. Together, our finding supports the further development of MCC5145 as a potential new treatment option for pneumonia and/or bacteremic pneumonia in clinical settings, particularly for immunocompromised individuals. IMPORTANCE S. pneumoniae (the pneumococcus) causes severe community acquired lung and blood infection, especially among the elderly and people with underlying medical conditions and/or weakened immune systems. The rising incidence of antibiotic resistance and delays between diagnosis of infection and commencement of effective therapy make treatment difficult and result in high mortality rates. In this work, we show that a new derivative (MCC5145) of an existing antibiotic (vancomycin) rapidly eradicated lethal pneumococcal challenge from the lungs and blood of mice with a suppressed immune system. Our findings support that MCC5145 is a promising option for the treatment of lung and blood infections caused by the pneumococcus at point-of-care settings, particularly for the elderly and individuals with a weakened immune system.

Methylparaben (MeP) is one of the most serious water pollutants found in cosmetic industry effluents. It interferes with various organisms' endocrine or hormonal systems and has been increasingly accumulating in water bodies because of its widespread use and high chemical stability, prompting the need for its mitigation. Plasmonic nanoparticles offer a promising pathway for pollutant removal in water treatment due to their ability to perform direct visible light-driven photocatalysis. In this regard, a hybrid catalyst of silver nanoparticles on reduced graphene oxide (rGO/AgNPs) was fabricated using biobased in situ reduction process and was employed as a visible light photocatalyst to treat MeP. The use of green reducing agents reduces the overall cost and environmental impact of the process. The synthesized catalyst exhibits significantly enhanced adsorption and photocatalytic degradation efficiency of MeP (97.6%) than rGO or AgNPs, individually. The conditions that influence the kinetics of the photocatalytic degradation by rGO/AgNPs were comprehensively studied using response surface methodology, including solution pH, catalyst dose, persulfate concentration, MeP initial concentration, and time. The nanocomposite showed high stability and could be used for several cycles without reducing the activity. Additionally, the mechanism of the photocatalytic reaction was investigated by scavenger tests and the density functional theory study. This approach provides new insights into the future research and development of low-cost photocatalysts for cosmetic wastewater treatment utilizing visible light irradiation.

Bacteria, similar to most organisms, have a love-hate relationship with metals: a specific metal may be essential for survival yet toxic in certain forms and concentrations. Metal ions have a long history of antimicrobial activity and have received increasing attention in recent years owing to the rise of antimicrobial resistance. The search for antibacterial agents now encompasses metal ions, nanoparticles and metal complexes with antimicrobial activity ('metalloantibiotics'). Although yet to be advanced to the clinic, metalloantibiotics are a vast and underexplored group of compounds that could lead to a much-needed new class of antibiotics. This Review summarizes recent developments in this growing field, focusing on advances in the development of metalloantibiotics, in particular, those for which the mechanism of action has been investigated. We also provide an overview of alternative uses of metal complexes to combat bacterial infections, including antimicrobial photodynamic therapy and radionuclide diagnosis of bacterial infections.

Antimicrobial resistance (AMR) is a global threat to society due to the increasing emergence of multi-drug resistant bacteria that are not susceptible to our last line of defence antibiotics. Exacerbating this issue is a severe gap in antibiotic development, with no new clinically relevant classes of antibiotics developed in the last two decades. The combination of the rapidly increasing emergence of resistance and scarcity of new antibiotics in the clinical pipeline means there is an urgent need for new efficacious treatment strategies. One promising solution, known as the 'Trojan horse' approach, hijacks the iron transport system of bacteria to deliver antibiotics directly into cells - effectively tricking bacteria into killing themselves. This transport system uses natively produced siderophores, which are small molecules with a high affinity for iron. By linking antibiotics to siderophores, to make siderophore antibiotic conjugates, the activity of existing antibiotics can potentially be reinvigorated. The success of this strategy was recently exemplified with the clinical release of cefiderocol, a cephalosporin-siderophore conjugate with potent antibacterial activity against carbapenem-resistant and multi-drug resistant Gram-negative bacilli. This review discusses the recent advancements in siderophore antibiotic conjugates and the challenges associated with the design of these compounds that need to be overcome to deliver more efficacious therapeutics. Potential strategies have also been suggested for new generations of siderophore-antibiotics with enhanced activity.

The tetrazole moiety is a versatile scaffold in medicinal chemistry due to its specific structure and essential roles in biosciences. Here, a supramolecular behavior of newly synthesized benzyl 2-[5-(benzyloxycarbonylaminomethyl)tetrazol-1-yl)-3-phenyl-propanoate, 1, was studied by single-crystal X-ray crystallography and computational techniques, and compared with 21 structurally diversified 1,5-disubsituted tetrazole-containing peptidederived structures, retrieved from the Cambridge Structure Database, providing a library of tetrazole-based Hbonding synthons reported for the first time. Hirshfeld surface analysis, followed by the enrichment ratios, demonstrates that the supramolecular assembly of this class of compounds was controlled mainly by O...H, N...H, C...H and pi-stacking interactions. Synergy of pi...pi and X-Y...pi (X=C, N; Y=H, F) inter-contacts leads to diverse supramolecular patterns. The 3D topologies of the supramolecular architectures were visualised via energy frameworks, revealing a high contribution of dispersion forces. Using a quantum-chemical treatment, the molecular electrostatic potential and the HOMO and LUMO levels designated the chemical activity and stability of the compound. The compilation of these findings provides valuable information that may eventually form the basis of the design of more effective therapeutic agents containing tetrazole motifs.

Antimicrobial resistance is an urgent threat to human health, and new antibacterial drugs are desperately needed, as are research tools to aid in their discovery and development. Vancomycin is a glycopeptide antibiotic that is widely used for the treatment of Gram-positive infections, such as life-threatening systemic diseases caused by methicillin-resistant Staphylococcus aureus (MRSA). Here we demonstrate that modification of vancomycin by introduction of an azide substituent provides a versatile intermediate that can undergo copper-catalysed azide−alkyne cycloaddition (CuAAC) reaction with various alkynes to readily prepare vancomycin fluorescent probes. We describe the facile synthesis of three probes that retain similar antibacterial profiles to the parent vancomycin antibiotic. We demonstrate the versatility of these probes for the detection and visualisation of Gram-positive bacteria by a range of methods, including plate reader quantification, flow cytometry analysis, high-resolution microscopy imaging, and single cell microfluidics analysis. In parallel, we demonstrate their utility in measuring outer-membrane permeabilisation of Gram-negative bacteria. The probes are useful tools that may facilitate detection of infections and development of new antibiotics.

INTRODUCTION:Antimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making.METHODS:A published and validated-dynamic health economic model was adapted to the Australian setting. Over a 10-year time horizon, the model estimates the clinical and economic outcomes associated with reducing current AMR levels, by up to 95%, of three gram-negative pathogens in three hospital-acquired infections, from the perspective of healthcare payers. A willingness-to-pay threshold of AUD$15,000-$45,000 per quality-adjusted life-year (QALY) gained and a 5% discount rate (for costs and benefits) were applied.RESULTS:Over ten years, reducing AMR for gram-negative pathogens in Australia is associated with up to 10,251 life-years and 8924 QALYs gained, 9041 bed-days saved and 6644 defined-daily doses of antibiotics avoided. The resulting savings are estimated to be $10.5 million in hospitalisation costs, and the monetary benefit at up to $412.1 million.DISCUSSION:Our results demonstrate the clinical and economic value of reducing AMR impact in Australia. Of note, since our analysis only considered a limited number of pathogens in the hospital setting only and for a limited number of infection types, the benefits of counteracting AMR are likely to extend well beyond the ones demonstrated here.CONCLUSION:These estimates demonstrate the consequences of failure to combat AMR in the Australian context. The benefits in mortality and health system costs justify consideration of innovative reimbursement schemes to encourage the development and commercialisation of new effective antimicrobials.

Population Medicine considers the following types of articles:• Research Papers -reports of data from original research or secondary dataset analyses.• Review Papers -comprehensive, authoritative, reviews within the journal's scope.These include both systematic reviews and narrative reviews.• Short Reports -brief reports of data from original research.• Policy Case Studies -brief articles on policy development at a regional or national level.• Study Protocols -articles describing a research protocol of a study.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.

Bacterial infections are a significant cause of mortality and morbidity worldwide, despite decades of use of numerous existing antibiotics and constant efforts by researchers to discover new antibiotics. The emergence of infections associated with antibiotic-resistant bacterial strains, has amplified the pressure to develop additional bactericidal therapies or new unorthodox approaches that can deal with antimicrobial resistance. Nanomaterial-based strategies, particularly those that do not rely on conventional small-molecule antibiotics, offer promise in part due to their ability to dodge existing mechanisms used by drug-resistant bacteria. Therefore, the use of nanomaterial-based formulations has attracted attention in the field of antibiotic therapy. In this Review, we highlight novel and emerging nanomaterial-based formulations along with details about the mechanisms by which nanoparticles can target bacterial infections and antimicrobial resistance. A detailed discussion about types and the activities of nanoparticles is presented, along with how they can be used as either delivery systems or as inherent antimicrobials, or a combination of both. Lastly, we highlight some toxicological concerns for the use of nanoparticles in antibiotic therapies.