Development of metals as antimicrobials: knowledge gaps and future directions.

Separation of chitin from shrimp shells enabled by transition metal salt aqueous solution and ionic liquid

Unprecedented explosion of research in the field of nanotechnology has gained importance in the treatment, prevention, and eradication of antibiotic-resistant bacterial strains. The emerging multidrug-resistant bacteria (MDRB) pose a major threat to the modern health-care system. The MDRB strains cannot be treated with conventional antibiotics due to their rapid mutations and resistance. Antibiotic-resistant bacteria that produce biofilm are responsible for approximately 700,000 deaths each year. One of the biggest problems faced by research society is to find alternatives to combat the increasing number of resistant variants. Photodynamic therapy (PDT) was established recently and remains a successful treatment modality for infectious diseases caused by microbial strains and biofilms. Light-mediated inactivation through photodynamic therapy provides new dimensions to eradicate antibiotic-resistant microbes. Antimicrobial photodynamic therapy (aPDT) has gained interest in nanotechnology where the effectiveness of photosensitizers (PS) can be enhanced by the use of nanoparticles (NPs). In the last two decades, different techniques have been raised for aPDT in combination with nanoparticles. Nanoparticles are used in aPDT either as photosensitizing agents or as PS delivery agents. Nanoparticles used in aPDT improve the dispersion and selective delivery of PS to the target cells. Over last decades, various nanoparticles are utilized in aPDT as nanocarriers. Polymeric nanovehicles, nanomicelles, and liposome are used to encapsulate PS molecules. The inorganic metallic nanoparticles are extensively studied for the photoinactivation of resistant microorganisms and their biofilms. The four types of combinations between nanoparticles and PS are categorized as nanoparticles embedded with PS, nanoparticles with PS bound to the surface, nanoparticles as the PS, and PS alongside nanoparticles. Nanoparticles have enhanced the activity of aPDT by encapsulating the PS in nanoparticles or binding the PS on the surface of nanoparticles covalently. The photoactive nanoparticles were successful as antimicrobial agents and more effective against antibiotic-resistant microbial strains and their biofilms.

Numerous studies have been performed in the field of Nd-Fe-B based permanent magnets since they possess excellent hard magnetic properties. The magnetic properties are closely related to the structure, phases present, processing route etc. High performance hard magnets can obtain their desired large energy product by interaction of magnetic moments at the nanoscale. Therefore, developing nanostructured Nd-Fe-B based magnets requires the study of novel synthesis techniques, microstructure and properties. Conventional physical techniques have limitations of inhomogeneity, contamination, poor control of microstructure and high cost due to the use of elemental rare earth metals. On the other hand, bottom-up chemical methods offer better control of structure at the nanoscale. The use of metal salts as precursors significantly reduces the cost. Hence, a cost-effective, bottom-up, microwave synthesis method is promising to produce homogenous particles by uniform microwave heating. The main objective of this project is the study of the microwave synthesis of Nd-Fe-B based magnets. The processing parameters, reaction mechanisms, characterization and property evaluation of these materials were carried out.

Environment, animals, and food as reservoirs of antibiotic-resistant bacteria for humans: One health or more?

The need for new antimicrobial agents is greater than ever because of the emergence of multidrug resistance in common pathogens, the rapid emergence of new infections, and the potential for use of multidrug-resistant agents in bioweapons. Paradoxically, some pharmaceutical companies have indicated that they are curtailing anti-infective research programs. We evaluated the United States Food and Drug Administration (FDA) databases of approved drugs and the research and development programs of the world's largest pharmaceutical and biotechnology companies to document trends in the development of new antimicrobial agents. FDA approval of new antibacterial agents decreased by 56% over the past 20 years (1998-2002 vs. 1983-1987). Projecting future development, new antibacterial agents constitute 6 of 506 drugs disclosed in the developmental programs of the largest pharmaceutical and biotechnology companies. Despite the critical need for new antimicrobial agents, the development of these agents is declining. Solutions encouraging and facilitating the development of new antimicrobial agents are needed.

Community composition and antibiotic resistance of tap water bacteria are still not known well enough. This study fills the gaps in knowledge regarding this matter. To provide representativeness of collected samples, tap water bacteria were concentrated from huge amounts of water, using filtration membranes monthly during the continuous, semi-annual study, covering winter and spring seasons. Biomass was investigated both using a culture-based method (for total and antibiotic-resistant culturable bacteria counts) and metagenomic DNA sequencing (for taxonomic identification of bacteria). The results showed that bacteria resistant to ceftazidime were the most prevalent among the studied resistance phenotypes, whereas bacteria resistant to amoxicillin, ciprofloxacin, and tetracycline were scarce. On average, 20,059 and 26,200 CFU/mL per month was counted in the winter and spring season, respectively, whereas in terms of antibiotic-resistant bacteria, average counts were 14,270 and 9435 CFU/mL per month in the winter and spring season, respectively. In terms of bacterial community composition, Cyanobacteria, Proteobacteria and Actinobacteria were the most abundant phyla, reaching up to 77.71%, 74.40% and 21.85%, respectively, which is supported by previous studies conducted on the same water supply network and other drinking water distribution systems across the world. No season-dependent variations were observed for culturable antibiotic-resistant bacteria or bacterial community composition. The prevalence of culturable antibiotic-resistant bacteria was not correlated with any of the identified taxa.

Herein, a one-pot synthesis of tetra-substituted imidazole, 4-chloro-2-(1-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazol-2-yl)phenol (HL), is reported by the reaction of benzil, 5-bromosalicylaldehyde, ammonium acetate and anisidine. The synthesized imidazole was reacted with salts of 1st row transition metals (Co(ii), Ni(ii), Cu(ii), Mn(ii) and Zn(ii)) to obtain metal complexes. The structure of the compounds was confirmed using various spectroscopic and analytical techniques. HL, which is crystalline, was characterized by SC-XRD. Subsequently, the synthesized compounds were evaluated for their antioxidant and antimicrobial activities. Antimicrobial studies revealed the more noxious nature of metal complexes compared to ligand against various strains of bacteria and fungi. Molecular docking results based on the binding energy values also supported the experimental results of the antioxidant activities of the compounds. HL was found to be a better antioxidant than metal complexes. For a better insight into the structure, computational studies of the compounds were also carried out. A clear intra-molecular charge transfer was perceived in the ligand and its metal complexes. The transfer integral values for holes (36.48 meV) were found to be higher than the electron transfer integrals (24.76 meV), which indicated that the ligand would be a better hole transporter. According to the frontier molecular orbitals of the dimer, the charge transfer within the molecule is found from monomer 1 to 2.

Antimicrobial resistance in bacteria is a threat to both human and animal health. We aimed to understand the impact of domestication and antimicrobial treatment on the types and numbers of resistant bacteria, antibiotic resistance genes (ARGs), and class 1 integrons (C1I) in the equine gut microbiome. Antibiotic-resistant fecal bacteria were isolated from wild horses, healthy farm horses, and horses undergoing veterinary treatment, and isolates (9,083 colonies) were screened by PCR for C1I; these were found at frequencies of 9.8% (vet horses), 0.31% (farm horses), and 0.05% (wild horses). A collection of 71 unique C1I+ isolates (17 Actinobacteria and 54 Proteobacteria) was subjected to resistance profiling and genome sequencing. Farm horses yielded mostly C1I+ Actinobacteria (Rhodococcus, Micrococcus, Microbacterium, Arthrobacter, Glutamicibacter, Kocuria), while vet horses primarily yielded C1I+ Proteobacteria (Escherichia, Klebsiella, Enterobacter, Pantoea, Acinetobacter, Leclercia, Ochrobactrum); the vet isolates had more extensive resistance and stronger PC promoters in the C1Is. All integrons in Actinobacteria were flanked by copies of IS6100, except in Micrococcus, where a novel IS5 family element (ISMcte1) was implicated in mobilization. In the Proteobacteria, C1Is were predominantly associated with IS26 and also IS1, Tn21, Tn1721, Tn512, and a putative formaldehyde-resistance transposon (Tn7489). Several large C1I-containing plasmid contigs were retrieved; two of these (plasmid types Y and F) also had extensive sets of metal resistance genes, including a novel copper-resistance transposon (Tn7519). Both veterinary treatment and domestication increase the frequency of C1Is in equine gut microflora, and each of these anthropogenic factors selects for a distinct group of integron-containing bacteria. IMPORTANCE There is increasing acknowledgment that a "one health" approach is required to tackle the growing problem of antimicrobial resistance. This requires that the issue is examined from not only the perspective of human medicine but also includes consideration of the roles of antimicrobials in veterinary medicine and agriculture and recognizes the importance of other ecological compartments in the dissemination of ARGs and mobile genetic elements such as C1I. We have shown that domestication and veterinary treatment increase the frequency of occurrence of C1Is in the equine gut microflora and that, in healthy farm horses, the C1I are unexpectedly found in Actinobacteria, while in horses receiving antimicrobial veterinary treatments, a taxonomic shift occurs, and the more typical integron-containing Proteobacteria are found. We identified several new mobile genetic elements (plasmids, insertion sequences [IS], and transposons) on genomic contigs from the integron-containing equine bacteria.

Species identification by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a routine diagnostic process for infectious diseases in current clinical settings. The rapid, low-cost, and simple to conduct methodology is expanding its application in clinical microbiology laboratories to diagnose the antimicrobial resistance (AMR) in microorganisms. Primarily, antimicrobial susceptibility testing is able to be carried out either by comparing the area under curve of MALDI spectra of bacteria grown in media with antimicrobial drugs or by identifying the shift peaks of bacteria grown in media including 13C isotope with antimicrobial drugs. Secondly, the antimicrobial resistance is able to be determined through identifying (i) the antimicrobial-resistant clonal groups based on the fingerprints of the clone, (ii) the shift peak of the modified antimicrobial drug, which is inactivated by the resistance determinant, (iii) the shift peak of the modified antimicrobial target, (iv) the peak specific for the antimicrobial determinant, and (v) the biomarkers that are coproduced proteins with AMR determinants. This review aims to present the current usage of the MALDI-TOF MS technique for diagnosing antimicrobial resistance in bacteria, varied approaches for AMR diagnostics using the methodology, and the future applications of the methods for the accurate and rapid identification of AMR in infection-causing bacterial pathogens.

A promising agent against wild-type and antibiotic-resistant bacteria using biogenic silver nanoparticles from Marphysa moribidii extract.

BackgroundAntibiotic resistance is one of the current threats to human health, forcing the use of drugs that are more noxious, costlier, and with low efficiency. There are several causes behind antibiotic resistance, including over-prescription of antibiotics in both humans and livestock. In this scenario, researchers are shifting to new alternatives to fight back this concerning situation. Scope and approachNanoparticles have emerged as new tools that can be used to combat deadly bacterial infections directly or indirectly to overcome antibiotic resistance. Although nanoparticles are being used in the pharmaceutical industry, there is a constant concern about their toxicity toward human health because of the involvement of well-known toxic chemicals (i.e., sodium/potassium borohydride) making their use very risky for eukaryotic cells. Key findings and conclusionsMultiple nanoparticle-based approaches to counter bacterial infections, providing crucial insight into the design of elements that play critical roles in the creation of antimicrobial nanotherapeutic drugs, are currently underway. In this context, plant-based nanoparticles will be less toxic than many other forms, which constitute promising candidates to avoid widespread damage to the microbiome associated with current practices. This article aims to review the actual knowledge on plant-based nanoparticle products for antibiotic resistance and the possible replacement of antibiotics to treat multidrug-resistant bacterial infections.

Solid state and solution photoluminescence properties of a novel meso–meso-linked porphyrin dimer Schiff base ligand and its metal complexes

Background: While concerns about the spread of Antimicrobial resistance (AMR) in HCF have long been identified, the links with environmental issues - such as water, sanitation, and hygiene (WASH) - are much less well understood. Indeed, misperceptions of links between WASH and AMR are identified as one of the hindrances of infection control programs. This study assessed the gap in knowledge in healthcare facilities (HCFs), by analyzing the perceptions of healthcare workers. Methods: A cross-sectional survey was conducted in governmental primary healthcare facilities in Gaza, Palestine between April and August 2022. Out of 1802 workers, 322 were randomly recruited to fill out a self-administer questionnaire. The workers were representing both genders (50.3% females) and aged between (19- 60 years). Data was analyzed using Statistical Package for Social Sciences (SPSS) software, version 23. Results: About half of the respondents (52.5%) did not know what the “WASH” term stands for, and nearly a quarter (22.7%) were unable to define AMR bacteria correctly. The perception of water safety was higher for domestic (66.1%) than for drinking water (54.7%) with a lower perception among females (p value=0.005) and medical staff (p value=0.000). At HCFs, only 40.7% of respondents had the perception that regular water safety monitoring occurs and 30.4% declared that water pollution was reported at their facilities. Only 20.0% of health workers think that they play a role in monitoring water safety and 24.8% think that they play a role in preventing and controlling AMR bacteria. Conclusion: Hybrid educational and awareness programs about water safety and prevention of AMR bacteria need to be implemented within the context of the One Health approach. The investment in WASH infrastructure at HCFs requires parallel investment in capacity building and raising awareness of workers.

This study reports the synthesis and characterization of Schiff base ligands derived from 4-hydroxybenzaldehyde and L-glycine. The Schiff base was synthesized using a base catalyst (Potassium hydroxide). The derived Schiff base was reacted with metal salts (Cobalt (II) chloride pentahydrate and Copper (II) sulphate pentahydrate) to form Schiff base-metal complexes. The synthesized Schiff base, (E)-2-(4-hydroxybenzylideneamino) acetic acid and its metal complexes were characterized using Fourier Transform-Infrared (FT-IR) spectroscopy and solubility in selected solvents. The antimicrobial activity of the synthesized complexes was evaluated against strains of Staphylococcus aureus, Escherichia coli using standard agar diffusion method. The result demonstrated that the metal complexes exhibited enhanced antimicrobial activity compared to the Schiff base. The result shows the potential of the complexes as antimicrobial agents, highlighting the importance of metal-amino acid interactions in enhancing biological activity.

Academic institutes are breeding grounds of innovation and the cradle of future clinical pharmacologists and pharmacometricians. However, there is a crisis looming over academic institutions; funding for research in clinical pharmacology is at an all-time low. This crisis of academic funding is no longer a well-kept secret. This crisis is at a national level and has far-reaching consequences. Federal funding for biomedical research in the United States doubled between 1998 and 2003 and fueled academic research nationally.This funding was considered key to maintaining the edge of the United States in the pharmaceutical and biotechnology industries. However, federal funding for biomedical research has been in decline since that time. Federal funding for biomedical research is estimated to be at least 25% less in inflation-adjusted dollars than it was in 2003, whereas demand for research dollars has skyrocketed.1-3 The increased demand for research money in the face of dwindling federal support may be attributed to several factors. Universities were able to expand their facilities and hire more faculty during the years of surplus funding and now must maintain those facilities and retain key faculty in the face of ever-shrinking federal dollars. Adding to the problem, public universities face decreased funding at the state level, as state governments attempt to balance their budgets. Other sources of funding, such as the pharmaceutical industry, have also dried up, as the industry itself comes under pressure to control costs and faces close scrutiny of its funding of academic research. Finally, the rising cost of conducting biomedical research (both as actual costs and the ever-increasing regulatory burden to conduct those studies) contributes to the problem, as even phase 1 clinical studies may now cost upwards of $4 million.4 As dire as things are for the biomedical research community as a whole, the situation is even worse when it comes to attracting major federal funding for research in the field of clinical pharmacology and pharmacometrics. The key characteristic of being a universally applicable field of research has a considerable downside; clinical pharmacology is a field without the face of a disease that the public cares about. There is no 5K race for “getting the dose right,” in contrast to diseases like breast cancer, diabetes, and AIDS. The public in general does not know what clinical pharmacology is and does not understand its role in the development of new medicines for the diseases that affect loved ones in their families and communities. This is even reflected in federal funding, where the National Institutes of Health (NIH) has traditionally funded basic research while being slow in funding clinical pharmacology–based research. The funding crisis may affect what kind of research is performed in academic institutions, as “fundability” takes precedence over good science. More time is now spent by researchers worrying about how to bring in funds rather than generating truly innovative ideas. The time that used to be spent brainstorming on the whiteboard that fueled and inspired great innovations and mentored and shaped future leaders in the field of clinical pharmacology and pharmacometrics is now spent on decorating, refining, and rewriting research proposals to make them “fundable.” As academic researchers compete for the same small share of grant money, they are realizing that they often need to abandon ambitious innovative ideas for more predictable, less innovative ones, which have higher chances of securing funding. This “risk aversion” has become a serious threat to the innovation engine of academic research in the field of clinical pharmacology and pharmacometrics. The dwindling chances to secure funding, less freedom for bold innovative research, and diminishing returns as the funding gets tighter is resulting in a mass exodus of clinical pharmacologists and pharmacometricians leaders and mentors from academia. Over the last decade as the academic funding crisis has increased in its severity, the faculty members, postdoctoral fellows, staff scientists, and graduate students engaged in innovative clinical pharmacology research in academia have drastically decreased in number. In discussing this funding crisis with respected academic researchers in the field of clinical pharmacology and pharmacometrics, I saw a common theme emerge: “It is a great time to do science, but a terrible time to be an academic researcher.” Unless the situation improves, we may lose key mentors and leaders in academia, resulting not only in lost innovative research in clinical pharmacology and pharmacometrics, but also in the dire consequences of losing an entire generation of future clinical pharmacologists and pharmacometricians. The American College of Clinical Pharmacology believes that it is time for the national clinical pharmacology and pharmacometrics societies to come together to highlight the seriousness of this issue. A quick solution is not forthcoming. First and foremost, these scientific societies need to work collaboratively to generate awareness regarding the field of clinical pharmacology in public and within the federal funding agencies such as the NIH, whether this is through public media social events, 5K races, or other platforms to bring together science and the general public and to create a face for the field. Collaborative partnerships between the pharmaceutical industry, national funding agencies, and academia for continued innovative research and education of future clinical pharmacologists and pharmacometricians will be an effective approach, but will require more than lip service—a true commitment to the field of clinical pharmacology is needed by funding agencies and academic institutions. An effective solution to keep innovative clinical pharmacology and pharmacometrics research flourishing in academia could be funding through development of consortia and cooperative arrangements, particularly precompetitive consortia comprising, for example, the pharmaceutical industry, federal funding agencies, and academia. The consortium model best fosters collaboration among stakeholders with common goals by sharing resources, knowledge, and expertise as well as sharing risk in the most effective way. Several successful examples of cooperative arrangements via consortium already exist, including the Biomarkers Consortium, the Predictive Safety and Toxicology Consortium, and the Patient Reported Outcomes Consortium.5 Innovation in clinical pharmacology and pharmacometrics for the advancement of optimal drug development is a common goal for academia, federal funding agencies, the pharmaceutical industry, and the public—precompetitive consortia could bring these together in an effective way to rescue clinical pharmacology and pharmacometrics from this existential funding crisis in academia. Acknowledged for valuable discussions are Jeffrey S. Barrett, PhD, FCP, Michael J. Fossler, PharmD, PhD, FCP, Mathangi Gopalakrishnan, PhD, Peter Wiernik, MD, Raimund Peter, PhD, Lorraine Rusch, PhD, and Krista Levy.