Threat Of Antibiotic Resistance Research Articles

Clostridioides difficile Infection: Diagnosis and Treatment Challenges.

Clostridioides difficile is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of C. difficile infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting C. difficile bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of C. difficile, placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in C. difficile involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different C. difficile strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in C. difficile, with an emphasis on CDI therapies.

In vitro evaluation of the immunomodulatory and wakame assimilation properties of Lactiplantibacillus plantarum strains from swine milk.

The emergence and spread of antibiotic resistance threat forced to explore alternative strategies for improving the resistance to pathogens in livestock production. Probiotic lactic acid bacteria represent an alternative for this objective. In this study, seven Lactiplantibacillus plantarum strains from porcine colostrum and milk were isolated, identified and characterized in terms of their abilities to modulate immunity in porcine intestinal epithelial (PIE) cells. Then, two potential immunoregulatory strains were studied in terms of their ability to utilize and grow in wakame (Undaria pinnafida). Isolates were identified by 16S rRNA gene and evaluated by studying their interaction with PIE cells. The expressions of peptidoglycan recognition proteins (PGRPs), nucleotide-binding oligomerization domain (NODs), host defense peptides (pBD), and type I interferons (IFNs) were evaluated by RT-qPCR. The strain 4M4417 showed a remarkable capacity to differentially regulate the expression of PGRP1, PGRP3, NOD1, NOD2, and pBD1 in PIE cells. On the other hand, the strain 4M4326 was the most efficient to improve the expression of IFN-α and IFN-β in PIE cells challenged with poly (I:C). Both L. plantarum 4M4326 and 4M4417 were characterized in terms of their ability to utilize wakame. Results demonstrated that both strains efficiently grew in wakame-based broth. Our results suggest that L. planatrum 4M4326 and 4M4417 are interesting candidates to develop immunomodulatory feeds based on wakame utilization. These new immunosynbiotic feeds could help to reduce severity of intestinal infections and improve immune health status in pigs.

Growth inhibition of Salmonella by Leuconostoc species isolated from buffalo milk curd

Traditional fermented products are considered to be a niche for microbial diversity. Probiotics offer a unique approach for addressing the threat of antibiotic resistance. Therefore, the aim of the present study was to isolate Leuconostoc spp. from Buffalo milk curd, an artisanal fermented dairy product in Bangladesh and assess their growth inhibition competence against Salmonella sp. A total of 50 isolates were isolated and purified from five freshly prepared buffalo milk curd samples using two different media, with glucose or sucrose as the carbon source. Among these pure isolates, 37 were identified as presumptive Leuconostoc spp. The biochemical identification using the VITEK 2 system confirmed that 59.5% of the isolates were Leuconostoc mesenteroides ssp. cremoris, while 40.5% were Leuconostoc pseudomesenteroides. Out of the identified isolates, twelve had a similarity of over 97%, and twenty-five had a similarity of less than 96%. Consequently, these twelve isolates were tested for their antimicrobial activity against Salmonella sp. using two in vitro methods, agar well diffusion and microbroth. The isolate M1L1 exhibited the highest inhibitory zone (15 mm) and showed 55.6% growth inhibition by the agar well diffusion and microbroth assay, respectively, suggesting a similar efficacy between the two methods. Notably, five other isolates also displayed inhibitory zones ranging from 13 to 15 mm and growth inhibition percentages of 37 to 52%. Overall, the isolated Leuconostoc spp. could be utilized as probiotics to combat pathogenic microorganisms. Ann. Bangladesh Agric. (2023) 27 (1): 93-104

Sensing Levofloxacin with an RNA Aptamer as a Bioreceptor.

To combat the growing threat of antibiotic resistance, environmental testing for antibiotic contamination is gaining an increasing role. This study aims to develop an easy-to-use assay for the detection of the fluoroquinolone antibiotic levofloxacin. Levofloxacin is used in human and veterinary medicine and has been detected in wastewater and river water. An RNA aptamer against levofloxacin was selected using RNA Capture-SELEX. The 73 nt long aptamer folds into three stems with a central three-way junction. It binds levofloxacin with a Kd of 6 µM and discriminates the closely related compound ciprofloxacin. Furthermore, the selection process was analyzed using a next-generation sequencing approach to better understand the sequence evolution throughout the selection. The aptamer was used as a bioreceptor for the development of a lateral flow assay. The biosensor exploited the innate characteristic of RNA Capture-SELEX to select aptamers that displace a complementary DNA oligonucleotide upon ligand binding. The lateral flow assay achieved a limit of visual detection of 100 µM. While the sensitivity of this assay constrains its immediate use in environmental testing, the present study can serve as a template for the selection of RNA aptamer-based biosensors.

Characterization and risk assessment of novel SXT/R391 integrative and conjugative elements with multidrug resistance in Proteus mirabilis isolated from China, 2018-2020.

Proteus mirabilis can transfer transposons, insertion sequences, and gene cassettes to the chromosomes of other hosts through SXT/R391 integrative and conjugative elements (ICEs), significantly increasing the possibility of antibiotic resistance gene (ARG) evolution and expanding the risk of ARGs transmission among bacteria. A total of 103 strains of P. mirabilis were isolated from 25 farms in China from 2018 to 2020. The positive detection rate of SXT/R391 ICEs was 25.2% (26/103). All SXT/R391 ICEs positive P. mirabilis exhibited a high level of overall drug resistance. Conjugation experiments showed that all 26 SXT/R391 ICEs could efficiently transfer to Escherichia coli EC600 with a frequency of 2.0 × 10-7 to 6.0 × 10-5. The acquired ARGs, genetic structures, homology relationships, and conservation sequences of 26 (19 different subtypes) SXT/R391 ICEs were investigated by high-throughput sequencing, whole-genome typing, and phylogenetic tree construction. ICEPmiChnHBRJC2 carries erm (42), which have never been found within an SXT/R391 ICE in P. mirabilis, and ICEPmiChnSC1111 carries 19 ARGs, including clinically important cfr, blaCTX-M-65, and aac(6')-Ib-cr, making it the ICE with the most ARGs reported to date. Through genetic stability, growth curve, and competition experiments, it was found that the transconjugant of ICEPmiChnSCNNC12 did not have a significant fitness cost on the recipient bacterium EC600 and may have a higher risk of transmission and dissemination. Although the transconjugant of ICEPmiChnSCSZC20 had a relatively obvious fitness cost on EC600, long-term resistance selection pressure may improve bacterial fitness through compensatory adaptation, providing scientific evidence for risk assessment of horizontal transfer and dissemination of SXT/R391 ICEs in P. mirabilis.IMPORTANCEThe spread of antibiotic resistance genes (ARGs) is a major public health concern. The study investigated the prevalence and genetic diversity of integrative and conjugative elements (ICEs) in Proteus mirabilis, which can transfer ARGs to other hosts. The study found that all of the P. mirabilis strains carrying ICEs exhibited a high level of drug resistance and a higher risk of transmission and dissemination of ARGs. The analysis of novel multidrug-resistant ICEs highlighted the potential for the evolution and spread of novel resistance mechanisms. These findings emphasize the importance of monitoring the spread of ICEs carrying ARGs and the urgent need for effective strategies to combat antibiotic resistance. Understanding the genetic diversity and potential for transmission of ARGs among bacteria is crucial for developing targeted interventions to mitigate the threat of antibiotic resistance.

Pyrrolidine-2,3-diones: heterocyclic scaffolds that inhibit and eradicate S. aureus biofilms.

The absence of novel antibiotic classes, coupled with the rising threat of antibiotic persistence and resistance, is pushing the world perilously close to a new pre-antibiotic era. Over 35 000 people die every year in the US as a consequence of antimicrobial-resistant infections. Bacterial biofilms further complicate this scenario, as they are inherently more resistant to antibiotic treatments. Currently, there are no approved single agent or adjuvant small molecules for treating biofilm-complicated infections. Herein, we report the synthesis and microbiological evaluation of a novel library of 25+ monomeric and dimeric pyrrolidine-2,3-dione scaffolds. These compounds have displayed improved aqueous solubility, potent anti-biofilm properties, a low MBEC-to-MIC ratio, and synergism with FDA-approved antimicrobials against biofilm infections, constituting a promising technology as antimicrobial adjuvants.

Prevention and potential remedies for antibiotic resistance: current research and future prospects.

The increasing threat of antibiotic resistance and shrinking treatment options for infections have pushed mankind into a difficult position. The looming threat of the return of the pre-antibiotic era has caused a sense of urgency to protect and conserve the potency of antibiotic therapy. One of the perverse effects of antibiotic resistance is the dissemination of its causative agents from non-clinically important strains to clinically important strains and vice versa. The popular saying "Prevention is better than cure" is appropriate for tackling antibiotic resistance. On the one hand, new and effective antibiotics are required; on the other hand, better measures for the use of antibiotics, along with increased awareness in the general public related to antibiotic use, are essential. Awareness, especially of appropriate antibiotic use, antibiotic resistance, its dissemination, and potential threats, can help greatly in controlling the use and abuse of antibiotics, and the containment of antibiotic resistance. Antibiotic drugs' effectiveness can be enhanced by producing novel antibiotic analogs or adding adjuvants to current antibiotics. Combinatorial therapy of antibiotics has proven successful in treating multidrug-resistant (MDR) bacterial infections. This review aims to highlight the current global situation of antibiotic resistance and discuss the methods used to monitor, prevent, inhibit, or reverse bacterial resistance mechanisms in the fight against antibiotic resistance.

Rationally designed protein A surface molecularly imprinted magnetic nanoparticles for the capture and detection of Staphylococcus aureus.

Staphylococcus aureus (S. aureus), a commensal organism found on the human skin, is commonly associated with nosocomial infections and exhibits virulence mediated by toxins and resistance to antibiotics. The global threat of antibiotic resistance has necessitated antimicrobial stewardship to improve the safe and appropriate use of antimicrobials; hence, there is an urgent demand for the advanced, cost-effective, and rapid detection of specific bacteria. In this regard, we aimed to selectively detect S. aureus using surface molecularly imprinted magnetic nanoparticles templated with a well-known biomarker protein A, specific to S. aureus. Herein, a highly selective surface molecularly imprinted polymeric thin layer was created on ∼250 nm magnetic nanoparticles (MNPs) through the immobilization of protein A to aldehyde functionalized MNPs, followed by monomer polymerization and template washing. This study employs the rational selection of monomers based on their computationally predicted binding affinity to protein A at multiple surface residues. The resulting MIPs from rationally selected monomer combinations demonstrated an imprinting factor as high as ∼5. Selectivity studies revealed MIPs with four-fold higher binding capacity (BC) to protein A than other non-target proteins, such as lysozyme and serum albumin. In addition, it showed significant binding to S. aureus, whereas negligible binding to other non-specific Gram-negative, i.e. Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), and Gram-positive, i.e. Bacillus subtilis (B. subtilis), bacteria. This MIP was employed for the capture and specific detection of fluorescently labeled S. aureus. Quantitative detection was performed using a conventional plate counting technique in a linear detection range of 101-107 bacterial cells. Remarkably, the MIPs also exhibited approximately 100% cell recovery from milk samples spiked with S. aureus (106 CFU mL-1), underscoring its potential as a robust tool for sensitive and accurate bacterial detection in dairy products. The developed MIP exhibiting high affinity and selective binding to protein A finds its potential applications in the magnetic capture and selective detection of protein A as well as S. aureus infections and contaminations.

Harnessing the potential of antimicrobial peptides: current advances and future applications

Antimicrobial peptides (AMPs) represent a promising class of naturally occurring molecules with diverse structures and functions, offering a potent defense mechanism against microbial pathogens. This review explores the multifaceted role of AMPs in combating infections and their potential applications in various fields, including medicine, agriculture, and biotechnology. We discuss the mechanisms of action of AMPs, their structural diversity, modes of synthesis, and recent advancements in enhancing their stability and efficacy. Furthermore, we highlight the therapeutic potential of AMPs in treating multidrug-resistant infections, their role as alternatives to conventional antibiotics, and their applications in wound healing, immunomodulation, and drug delivery systems. Additionally, we examine the challenges associated with the clinical translation of AMPs and propose strategies to overcome these hurdles. Overall, this review underscores the importance of AMPs as versatile antimicrobial agents and emphasizes their potential to address the growing threat of antibiotic resistance.

Extended Spectrum Beta Lactamase Profile of Citrobacter Species Isolated from Various Samples in the North East Coast of Tamil Nadu, India: A Cross-sectional Study

Introduction: Citrobacter species play a significant role in causing hospital-acquired infections, especially those affecting the urinary and respiratory systems, and they are commonly present in faeces. Healthcare systems are facing a major challenge due to the rise of antibiotic-resistant Gram-negative infections resistant to antibiotics. Aim: To identify the genotypic characterisation of the resistant gene blaTEM-1 in Citrobacter spp. obtained from a range of clinical samples. This investigation seeks to provide insights into the patterns of antibiotic resistance exhibited by these bacteria. Materials and Methods: This cross-sectional study was conducted between August 2021 and February 2022. Preliminary examinations included screening as well as confirmatory tests for Extended Spectrum Beta Lactamase (ESBL) production, which were confirmed by the combination disk method and double disc synergy test. Genotypic detection of the blaTEM-1 gene was done using the Polymerase Chain Reaction (PCR) technique. Demographic parameters like gender and age were assessed. Statistical analysis was done using the Statistical Package for the Social Sciences (SPSS) Software version 21.0. Results: Citrobacter koseri (66 isolates, 54.5%) was found to be the predominant species among the Citrobacter spp., followed by Citrobacter freundii (55 isolates, 45.5%). Urine samples were the primary source of Citrobacter spp. isolates, comprising 52 isolates (43%) of the total. In this study, the prevalence of ESBL producers was reported to be 49 isolates (77.8%) identified as ESBL producers. Tigecycline demonstrated a 100% effectiveness rate, followed by Piperacillin-Tazobactam (96% sensitivity) and Amikacin (95% sensitivity). Out of the 20 Citrobacter spp. isolates that tested positive for ESBL, 15 isolates (75%) were found to be positive for blaTEM-1. Conclusion: The results of this study provide insight into the changing patterns of antibiotic resistance in Citrobacter spp., with particular emphasis on ESBL profiles. Thus, it is imperative to implement intervention techniques to reduce the ongoing selection and spread of these more resistant bacteria, as well as efficient infection-control measures to manage epidemics. These results advance the comprehension of antibiotic resistance patterns and guide initiatives to combat the increasing threat of antibiotic resistance.

Antibiotic adjuvants: synergistic tool to combat multi-drug resistant pathogens.

The rise of multi-drug resistant (MDR) pathogens poses a significant challenge to the field of infectious disease treatment. To overcome this problem, novel strategies are being explored to enhance the effectiveness of antibiotics. Antibiotic adjuvants have emerged as a promising approach to combat MDR pathogens by acting synergistically with antibiotics. This review focuses on the role of antibiotic adjuvants as a synergistic tool in the fight against MDR pathogens. Adjuvants refer to compounds or agents that enhance the activity of antibiotics, either by potentiating their effects or by targeting the mechanisms of antibiotic resistance. The utilization of antibiotic adjuvants offers several advantages. Firstly, they can restore the effectiveness of existing antibiotics against resistant strains. Adjuvants can inhibit the mechanisms that confer resistance, making the pathogens susceptible to the action of antibiotics. Secondly, adjuvants can enhance the activity of antibiotics by improving their penetration into bacterial cells, increasing their stability, or inhibiting efflux pumps that expel antibiotics from bacterial cells. Various types of antibiotic adjuvants have been investigated, including efflux pump inhibitors, resistance-modifying agents, and compounds that disrupt bacterial biofilms. These adjuvants can act synergistically with antibiotics, resulting in increased antibacterial activity and overcoming resistance mechanisms. In conclusion, antibiotic adjuvants have the potential to revolutionize the treatment of MDR pathogens. By enhancing the efficacy of antibiotics, adjuvants offer a promising strategy to combat the growing threat of antibiotic resistance. Further research and development in this field are crucial to harness the full potential of antibiotic adjuvants and bring them closer to clinical application.

Cross-sectional study: knowledge assessment of youth regarding the global public health threat of antibiotic resistance

Cross-sectional study: knowledge assessment of youth regarding the global public health threat of antibiotic resistance

Neisseria gonorrhoeae Antimicrobial Resistance: The Future of Antibiotic Therapy.

The growing threat of antibiotic-resistant Neisseria gonorrhoeae, which causes gonorrhea, presents a current public health challenge. Over the years, the pathogen has developed resistance to different antibiotics, leaving few effective treatment options. High-level resistance to key drugs, including ceftriaxone, has become a concerning reality. This article primarily focuses on the treatment of gonorrhea and the current clinical trials aimed at providing new antibiotic treatment options. We explore ongoing efforts to assess new antibiotics, including zoliflodacin, and gepotidacin. These drugs offer new effective treatment options, but their rapid availability remains uncertain. We delve into two ongoing clinical trials: one evaluating the efficacy and safety of gepotidacin compared to the standard ceftriaxone-azithromycin combination and the other assessing the non-inferiority of zoliflodacin versus the combination therapy of ceftriaxone-azithromycin. These trials represent crucial steps in the search for alternative treatments for uncomplicated gonorrhea. Notably, gonorrhea has been included in the "WHO Priority Pathogens List for Research and Development of New Antibiotics". In conclusion, the urgent need for innovative treatment strategies is underscored by the rising threat of antibiotic resistance in N. gonorrhoeae; collaboration among researchers, industries, and healthcare authorities is therefore essential.

Antimicrobial Resistance Profiles of Multidrug-Resistant Enterobacteria Isolated from Feces of Weaned Piglets.

Nosocomial infections caused by multidrug-resistant enterobacteria have become a major challenge in global public health. Previous studies have indicated that use of antibiotics in livestock production chains is linked to the rising threat of antibiotic resistance in humans. In this study, we aimed to evaluate the distribution of genes encoding resistance to tetracycline, β-lactams, and colistin in multidrug-resistant enterobacteria isolated from feces of weaned pigs. Ninety-four enterobacteria isolates were submitted to antibiotic susceptibility test by minimum inhibitory concentration (MIC). In addition, we performed conjugation experiments to verify if plasmid-bearing isolates containing the mcr-1 gene could transfer their resistance determinant to a colistin-sensitive recipient strain. Our results demonstrated a positive association between the detection of antibiotic resistance genes in enterobacteria and the phenotypic resistance profiles of the bacterial isolates. At least one of the extended-spectrum β-lactamases (ESBL) genes (blaCTX-M, blaTEM, or bla SHV) and tetA was found among most bacterial genera analyzed. In addition, results revealed that the mcr-1 gene can be transferred from E. coli UFV-627 isolate to an F- recipient (Escherichia coli K12) by conjugation. Our findings support the hypothesis that swine represents an important reservoir of antibiotic resistance genes and suggest that horizontal transfer mechanisms (e.g., conjugation) may mediate the spread of these genes in the swine gastrointestinal tract.

Therapeutic proteins have the potential to become new weapons in the fight against antibiotic resistance

Humans are continually challenged to find new strategies to fight bacterial diseases due to the global health threat of antibiotic resistance. Conventional antibiotics, once hailed as miracle treatments, are progressively losing their effectiveness as drug-resistant bacteria continue to emerge, including multidrug-resistant (MDR) strains. An attractive approach to solving the antibiotic resistance problem is the investigation of other methods, such as therapeutic proteins. Here, we begin with a discussion of antimicrobial resistance and common strategies that bacteria employ to become resistant. Next, we discuss the potential use of antimicrobial peptides and monoclonal antibodies, two types of therapeutic proteins, as possible antimicrobial therapeutics. We discuss their structure, mechanism of action, and highlight examples of possible candidate molecules for clinical use. Finally, we discuss the remaining challenges and explore potential solutions for the implementation of therapeutic proteins into practical clinical use.

Efficacy of the bee-venom antimicrobial peptide Osmin against sensitive and carbapenem-resistant Klebsiella pneumoniae strains

The emergence of multidrug-resistant (MDR) Klebsiella pneumoniae strains causes severe problems in the treatment of bacterial infections owing to limited treatment options. Especially, carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly spreading worldwide and is emerging as a new cause of drug-resistant healthcare-associated infections. CRKP also has been announced by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) as one of the most pressing antibiotic resistance threats. Antimicrobial peptides (AMPs) are drawing considerable attention as ideal antibiotic alternative candidates to combat MDR bacterial infections. In a previous study, Osmin is composed of 17 amino acids and is isolated from solitary bee (Osmia rufa) venom. Herein, we evaluated the potential of Osmin to be used against drug-resistant K. pneumoniae as an alternative to conventional antibiotics. Osmin exhibited significant antimicrobial and anti-biofilm activity and lower toxicity than melittin, a well-known bee venom peptide. Additionally, we confirmed that it possesses a bactericidal mechanism that rapidly destroys bacterial membranes. Osmin was relatively more stable than melittin under the influence of various environmental factors and unlike conventional antibiotics, it exhibited a low bacterial resistance risk. During in vivo tests, Osmin reduced bacterial growth and the expression of pro-inflammatory cytokines and fibrosis-related genes in mice with CRKP-induced sepsis. Overall, our results indicate a high potential for Osmin to be used as a valuable therapeutic agent against drug-resistant K. pneumoniae infections.

The Relationship Between the Microbiome and Antimicrobial Resistance.

Antibiotics have benefitted human health since their introduction nearly a century ago. However, the rise of antibiotic resistance may portend the dawn of the "post-antibiotic age." With the narrow pipeline for novel antimicrobials, we need new approaches to deal with the rise of multidrug resistant organisms. In the last 2 decades, the role of the intestinal microbiota in human health has been acknowledged and studied widely. Of the various activities carried out by the gut microbiota, colonization resistance is a key function that helps maintain homeostasis. Therefore, re-establishing a healthy microbiota is a novel strategy for treating drug resistance organisms. Preliminary studies suggest that this is a viable approach. However, the extent of their success still needs to be examined. Herein, we will review work in this area and suggest where future studies can further investigate this method for dealing with the threat of antibiotic resistance.

Progress on mechanisms of antibiotic resistance in Clostridioides difficile.

Clostridioides difficile (CD) is one of the most common pathogens causing health-care-associated infectious diarrhea and is listed by the U.S. Centers for Disease Control and Prevention as an urgent antibiotic resistance (AR) threat. Many resistance genes can be transferred between different CD strains present in the clinical setting, community, and environment. The antimicrobial resistance (AMR) of CD continues to evolve with the emergence and acquisition of new drug resistance mechanisms. CD has developed diverse drug resistance mechanisms, such as drug alteration, modification of the target site, and extrusion of drugs via efflux pumps. Researches have provided comprehensive knowledge about resistance mechanisms of macrolides and quinolones in CD. However, the mechanisms of resistance for metronidazole, vancomycin, and other therapeutic antibiotics against Clostridioides difficile infection (CDI) are only beginning to be elucidated. Some previously unfound mechanisms, such as plasmid-mediated drug resistance in CD, may also play an important role. In this review, we summarize the research progress on drug resistance mechanisms of CD with antimicrobial drugs already used clinically, such as metronidazole, vancomycin, and fidaxomicin, thereby providing the references for the clinical treatment and prevention of CDI, as well as the development of new antibacterial drugs and detection kits for drug resistant bacteria.

Design, synthesis, theoretical studies, and biological activity evaluation of new nitrogen-containing poly heterocyclic compounds as promising antimicrobial agents

The increasing threat of antibiotic resistance has led to a pressing need for the development of new antimicrobial agents. Nitrogen-containing heterocycles are widely used in the development of drugs due to their broad spectrum of pharmacological activities, including antimicrobial properties. In this study, a series of 13 hybrid molecules containing two to four nitrogen heterocycles were designed using the molecular hybridization approach. The synthesized compounds were characterized and their antimicrobial properties were examined against two bacterial strains and a Candida strain. The most promising compounds were found to be those bearing the quinoline unit, exhibiting a MIC of less than 31.25 μg/mL against S. typhimurium and Bacillus subtilis. Molecular docking studies revealed that these compounds have excellent affinity with the DNA gyrase enzyme, making them potential candidates for further development as antimicrobial agents.

Development of antibacterial neural stimulation electrodes via hierarchical surface restructuring and atomic layer deposition.

Miniaturization and electrochemical performance enhancement of electrodes and microelectrode arrays in emerging long-term implantable neural stimulation devices improves specificity, functionality, and performance of these devices. However, surgical site and post-implantation infections are amongst the most devastating complications after surgical procedures and implantations. Additionally, with the increased use of antibiotics, the threat of antibiotic resistance is significant and is increasingly being recognized as a global problem. Therefore, the need for alternative strategies to eliminate post-implantation infections and reduce antibiotic use has led to the development of medical devices with antibacterial properties. In this work, we report on the development of electrochemically active antibacterial platinum-iridium electrodes targeted for use in neural stimulation and sensing applications. A two-step development process was used. Electrodes were first restructured using femtosecond laser hierarchical surface restructuring. In the second step of the process, atomic layer deposition was utilized to deposit conformal antibacterial copper oxide thin films on the hierarchical surface structure of the electrodes to impart antibacterial properties to the electrodes with minimal impact on electrochemical performance of the electrodes. Morphological, compositional, and structural properties of the electrodes were studied using multiple modalities of microscopy and spectroscopy. Antibacterial properties of the electrodes were also studied, particularly, the killing effect of the hierarchically restructured antibacterial electrodes on Escherichia coli and Staphylococcus aureus-two common types of bacteria responsible for implant infections.