Multidrug-resistant Pathogenic Bacteria Research Articles

Antimicrobial activity of cell-free supernatant derived from Ligilactobacillus animalis SWLA-1 in a novel ex vivo canine corneal infection model.

Canine bacterial keratitis is a corneal infection that causes various symptoms, including visual impairment, and necessitates eye removal in severe cases. Staphylococcus pseudintermedius is a pathogen that causes significant bacterial keratitis in canine patients. Moreover, multi-drug resistant Staphylococcus pseudintermedius (MDRSP) has been reported in both humans and animals. Regarding treatment failure against multi-drug resistant (MDR) pathogens with classic antibiotics, antimicrobial compounds derived from probiotics have been suggested as an alternative approach. Ligilactobacillus animalis SWLA-1 strain and its cell-free supernatant (CFS) have previously demonstrated potent antimicrobial activity against various MDR pathogenic bacteria. Based on this finding, we evaluated the anti-staphylococcal activity of CFS derived from Ligilactobacillus animalis SWLA-1 against MDRSP in a newly established ex vivo canine corneal infection model using fresh canine corneoscleral rims. Additionally, an in vitro cytotoxicity test using human keratocytes was performed. CFS significantly inhibited the growth of MDRSP in the novel ex vivo model and did not exhibit any significant toxicity against keratocytes in vitro. Based on these results, the antimicrobial compounds in CFS show potential as a novel approach for MDR staphylococcal keratitis treatment.

Antimicrobial Properties and Cytotoxicity of Iron Oxide Nanoparticles Synthesized Using Melia azedarach Leaf Extract Against Diarrhoeal Pathogens

AbstractThe high mortality and morbidity resulting from an increasing incidence of antibiotic resistance among pathogens highlight a crucial need for the development of novel alternative therapy. In the quest for alternative therapy, this study was conducted to synthesise nanoparticles (NPs) from ferric chloride hexahydrate (FeCl3.6H2O) via Melia azedarach L. (Meliaceae) leaf extract and evaluate their antibacterial properties against multidrug resistant pathogenic Escherichia coli, Salmonella enterica, and Vibrio cholerae. Multidrug-resistant pathogenic bacteria were isolated from cattle faeces and characterised by whole genome sequence analysis. The extracts from M. azedarach leaves were used as reducing, capping, and stabilising agents on the precursor metal (FeCl3.6H2O) to produce NPs. The biosynthesised NPs were characterised by ultraviolent visible (UV–vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectrophotometry (FTIR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The NPs were tested against multidrug-resistant bacteria to determine the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and rate of kill. In this study, WGS analysis confirmed the bacteria (E. coli, V. cholerae, and S. enterica) isolates to be multidrug-resistant pathogen and NP that has a spherical shape with an average particle size of 49.75 nm was successfully biosynthesised. The NPs displayed significant antimicrobial activities with MIC of 62, 31, and 62 mg/mL, MBC of 500, 250, and 500 µg/mL, and the lowest killing times of 4, 2, and 3 h against E. coli, V. cholerae, and S. enterica, respectively. Interestingly, the concentrations of the NPs required to inhibit the growth of E. coli, V. cholerae, and S. enterica were not toxic to HEK293 cells. Based on the promising antimicrobial activities of the biosynthesised NPs in this study, they could be useful in important therapeutic applications aimed at combating multidrug-resistant pathogens.

Retrospective Analysis of Antimicrobial Susceptibility Pattern of Pseudomonas aeruginosa from Clinical Samples of Dogs in Grenada, West Indies

Background: Clinical infections caused by multidrug-resistant pathogenic bacteria are associated with increased morbidity and mortality, imposing a severe economic burden. Pseudomonas aeruginosa, a gram-negative bacterium, had demonstrated a prominent level of acquired antimicrobial resistance to its selective antimicrobials. Currently, there is no updated information about the antimicrobial susceptibility pattern of Pseudomonas aeruginosa in Grenada. Hence, the present study aimed to determine the antimicrobial susceptibility pattern of P. aeruginosa from the clinical isolates of dogs in Grenada. Methods: This retrospective study used the diagnostic reports from January 2015 to December 2022. The diagnostic microbiology laboratory reports of canine patients at the Small Animal Clinic of St. George’s University in Grenada were analyzed to study the antimicrobial susceptibility pattern of P. aeruginosa. Result: Among the various bacterial clinical isolates, ninety-one clinical samples were positive for P. aeruginosa. The antimicrobial susceptibility test pattern of these isolates revealed susceptibility to gentamicin (95.6 %), ceftazidime (96.7%), imipenem (97.7%) and ciprofloxacin (97.8%). The result of the present retrospective study illustrates that P. aeruginosa isolates from canine patients in Grenada are susceptible to the recommended antimicrobial drugs. However, this study also revealed the recent development of progressive antimicrobial resistance. This mandates the judicious use of antibacterial drugs against bacterial infections in Grenada.

LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases.

Antimicrobial peptides (AMPs), as well as host defense peptides (HDPs), constitute the first line of defense as part of the innate immune system. Humans are known to express antimicrobial precursor proteins, which are further processed to generate AMPs, including several types of α/β defensins, histatins, and cathelicidin-derived AMPs like LL37. The broad-spectrum activity of AMPs is crucial to defend against infections caused by pathogenic bacteria, viruses, fungi, and parasites. The emergence of multi-drug resistant pathogenic bacteria is of global concern for public health. The prospects of targeting antibiotic-resistant strains of bacteria with AMPs are of high significance for developing new generations of antimicrobial agents. The 37-residue long LL37, the only cathelicidin family of AMP in humans, has been the major focus for the past few decades of research. The host defense activity of LL37 is likely underscored by its expression throughout the body, spanning from the epithelial cells of various organs-testis, skin, respiratory tract, and gastrointestinal tract-to immune cells. Remarkably, apart from canonical direct killing of pathogenic organisms, LL37 exerts several other host defense activities, including inflammatory response modulation, chemo-attraction, and wound healing and closure at the infected sites. In addition, LL37 and its derived peptides are bestowed with anti-cancer and anti-amyloidogenic properties. In this review article, we aim to develop integrative, mechanistic insight into LL37 and its derived peptides, based on the known biophysical, structural, and functional studies in recent years. We believe that this review will pave the way for future research on the structures, biochemical and biophysical properties, and design of novel LL37-based molecules.

Genomic Characterization of Multidrug-Resistant Pathogenic Enteric Bacteria from Healthy Children in Osun State, Nigeria.

Antimicrobial resistance (AMR) is responsible for the spread and persistence of bacterial infections. Surveillance of AMR in healthy individuals is usually not considered, though these individuals serve as reservoirs for continuous disease transmission. Therefore, it is essential to conduct epidemiological surveillance of AMR in healthy individuals to fully understand the dynamics of AMR transmission in Nigeria. Thirteen multidrug-resistant Citrobacter spp., Enterobacter spp., Klebsiella pneumoniae, and Escherichia coli isolated from stool samples of healthy children were subjected to whole genome sequencing (WGS) using Illumina and Oxford nanopore sequencing platforms. A bioinformatics analysis revealed antimicrobial resistance genes such as the pmrB_Y358N gene responsible for colistin resistance detected in E. coli ST219, virulence genes such as senB, and ybtP&Q, and plasmids in the isolates sequenced. All isolates harbored more than three plasmid replicons of either the Col and/or Inc type. Plasmid reconstruction revealed an integrated tetA gene, a toxin production caa gene in two E. coli isolates, and a cusC gene in K. quasivariicola ST3879, which induces neonatal meningitis. The global spread of AMR pathogenic enteric bacteria is of concern, and surveillance should be extended to healthy individuals, especially children. WGS for epidemiological surveillance will improve the detection of AMR pathogens for management and control.

Isolation of Biofilm Removing Bacteriophages from the Hot Spring of Mae Chan Fault, Chiang Rai, Northern Thailand

T errestrial hot springs offer unique habitats for various bacteriophages, revealing potential reservoirs and a library for antibiotic-resistant and biofilm-removing bacteriophages. This study aimed to identify biofilm-removing bacteriophages as a potential method to eradicate antibiotic-resistant bacteria. Samples were collected from the Mae Chan Fault geothermal sites in Chiang Rai province, north of Thailand. Our bacteriophages, HSPT1 and HSPT2, effectively infect Pseudomonas aeruginosa TISTR1287, as measured by their plaque sizes (3.23 ± 0.26 mm) and (1.14 ± 0.18 mm), respectively. Thermostability analysis reveals that the optimal temperature for bacteriophage HSPT1 is between 20 and 60 oC, while for bacteriophage HSPT2, it is between 20 and 40 oC. Biofilm biomass was significantly reduced by the bacteriophages HSPT1 and HSPT2 treatments (1.42 ± 0.81 and 2.51 ± 0.71, respectively). The study reveals that hot spring bacteriophages effectively remove bacterial biofilms, proving their potential as a new treatment option for antibiotic-resistant bacteria in clinical and tourism settings. These bacteriophages, derived from hot springs, have effectively reduced biofilm-forming microorganisms and multidrug-resistant pathogenic bacteria.

Advanced nanozymes possess peroxidase-like catalytic activities in biomedical and antibacterial fields: review and progress.

Infectious diseases caused by bacterial invasions have imposed a significant global health and economic burden. More worryingly, multidrug-resistant (MDR) pathogenic bacteria born under the abuse of antibiotics have further escalated the status quo. Nowadays, at the crossroads of multiple disciplines such as chemistry, nanoscience and biomedicine, nanozymes, as enzyme-mimicking nanomaterials, not only possess excellent bactericidal ability but also reduce the possibility of inducing resistance. Thus, nanozymes are promising to serve as an alternative to traditional antibiotics. Nanozymes that mimic peroxidase (POD) activity are also known as POD nanozymes. In recent years, POD nanozymes have become one of the most frequently reported and effective nanozymes due to their broad-spectrum bactericidal properties and unique sterilization mechanism. In this review, we introduce the mechanism as well as the classification of POD nanozymes. More importantly, to further improve the antibacterial efficacy of POD nanozymes, we elaborate on three aspects: (1) improving the physicochemical properties; (2) regulating the catalytic microenvironment; and (3) designing multimodel POD nanozymes. In addition, we review the nanosafety of POD nanozymes for discussing their potential toxicity. Finally, the remaining challenges of POD nanozymes and possible future directions are discussed. This work provides a systematic summary of POD nanozymes and hopefully contributes to the early clinical translation.

Traditional Knowledge Driven Screening of 30 Medicinal Plants from Gandhmardhan, Odisha, That are Effective Against Human Multidrug Resistant Pathogenic Bacteria

The medico folklore use of medicinal plants is the mainstay healthcare system of the tribals in and around the Gandhamardan, Western Odisha. These people depend on the forest and traditional Vaidyas to treat various health ailments, including bacterial infections. While documenting folklore claims, we found the acute dependency of traditional diarrhoea on 30 medicinal plants from the Gandhamardan for treating respiratory tract infections, skin diseases, wound infections, diarrhoea, and dysentery. The plant parts of these plants were collected from the wild, and their phytochemical composition was determined using aqueous and ethanol extracts. The crude extracts at different concentrations were used to elucidate their antibacterial activity based on the zone of inhibition using the agar well diffusion method using eight pathogenic bacteria. The plant extracts revealed the presence of eight secondary metabolites, viz. alkaloids, glycosides, terpenoids, reducing sugar, saponins, tannins, flavonoids, and steroids. All 30 plants were very effective against all the MDR bacteria. The study would provide a scientific basis for clandestine ethnobotanical knowledge that would benefit the antimicrobial stewardship program.

Antibiotic susceptibility and virulence factors of bacterial species among cancer patients

Antibiotic resistance is one of the most significant challenges of the 20-s century, and the misuse of antibiotics is a driver of antimicrobial resistance. This study aimed to assess the prevalence of multidrug resistance, and detection of its produce virulence factors, including extended-spectrum β-lactamases (ESβLs), biofilm, and siderophores produced by bacterial species isolated from cancer patients. One hundred and seventy-five Gram-negative bacterial isolates were isolated from different samples collected from cancer patients admitted to the National Cancer Institute (NCI), Cairo, Egypt, and processed by standard microbiological methods. One hundred and forty-three bacterial isolates were recovered from adult patients, and 32 were recovered from children. Escherichia coli showed the highest frequency (36%), followed by Klebsiella pneumonia (30.85%), Acinetobacter baummannii (14.28%), and Pseudomonas sp. (9.14%). Antibiotic profiles revealed that bacterial isolates are highly resistant to the most commonly available antibiotics. Amikacin and gentamicin were the most effective antibiotics against isolated Gram-negative bacteria. Moreover, the vast majority of bacterial stains produce virulence factors, including EsβLs, biofilm, and siderophores. E. coli isolates produced ESβLs with rates of 25.28%, Klebsiella pneumonia (11.0%), and Pseudomonas sp. (25.0%). Among these collected bacterial isolates, 132 (75.4%) have the ability to form a biofilm to different degrees. Also, the majority of the bacteria isolates generated siderophores, with 133 (75.94%). This study revealed that a significant distribution of multidrug-resistant pathogenic bacteria may increase the burden on healthcare to prevent infections in cancer patients.

Antimicrobial Cyclic Dipeptides from Japanese Quail (Coturnix japonica) Eggs Supplemented with Probiotic Lactobacillus plantarum.

Fifteen cyclic dipeptides (CDPs) containing proline, one cyclo(Phe-Ala) without proline, and a non-peptidyl DL-3-phenyllactic acid were previously identified in the culture filtrates of Lactobacillus plantarum LBP-K10, an isolate from kimchi. In this study, we used Japanese quail (Coturnix japonica) eggs to examine the effects of probiotic supplementation on the antimicrobial CDPs extracted from quail eggs (QE). Eggshell-free QE were obtained from two distinct groups of quails. The first group (K10N) comprised eggs from unsupplemented quails. The second group (K10S) comprised eggs from quails supplemented with Lb. plantarum LBP-K10. The QE samples were extracted using methylene chloride through a liquid-liquid extraction process. The resulting extract was fractionated into 16 parts using semi-preparative high-performance liquid chromatography. Two fractions, Q6 and Q9, were isolated from K10S and identified as cis-cyclo(L-Ser-L-Pro) and cis-cyclo(L-Leu-L-Pro). The Q9 fraction, containing cis-cyclo(L-Leu-L-Pro), has shown significant inhibitory properties against the proliferation of highly pathogenic multidrug-resistant bacteria, as well as human-specific and phytopathogenic fungi. Some of the ten combinations between the remaining fourteen unidentified fractions and two fractions, Q6 and Q9, containing cis-cyclo(L-Ser-L-Pro) and cis-cyclo(L-Leu-L-Pro) respectively, demonstrated a significant increase in activity against multidrug-resistant bacteria only when combined with Q9. The activity was 7.17 times higher compared to a single cis-cyclo(L-Leu-L-Pro). This study presents new findings on the efficacy of proline-containing CDPs in avian eggs. These CDPs provide antimicrobial properties when specific probiotics are supplemented.

Silver nanoparticles synthesized by probiotic bacteria and antibacterial role in resistant bacteria

Many dangerous bacteria have become highly resistant to traditional antibiotics, which is a huge public health concern. This study investigated the use of silver nanoparticles biosynthesized in a culture filtrate of Lactobacillus acidophilus as antimicrobials. UV–visual spectrophotometry, Fourier-transform-infrared spectroscopy, X-ray power diffraction, and scanning electron microscopy have all validated the findings. The biosynthesized nanoparticles ranged in size from 33 to 90 nm. The cytotoxicity of the nanosilver generated was then investigated using nine 200 g BW rats separated into three groups. When compared to the control group, the treated rats showed little signs of toxicity; parameters of physiological function, including alanine transaminase, aspartate aminotransferase, albumin, creatinine, and urea were significantly different in treated and non-treated animals. Moreover, the antibacterial role of the generated silver nanoparticles was examined in multi-drug resistant (MDR) pathogenic bacteria, Proteus vulgaris, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae, revealing high antibacterial activity against the examined bacteria. For more demonstration of the effect of the nanosilver on transcription and gene regulation of treated and non-treated bacteria differential display droplet digital-PCR was used, and the results revealed that several genes were up- and down-regulated. Some genes were selected for DNA sequencing and according to the sequence analysis, these genes were mecA, beta-lactam, and unidentified protein genes, and these have been deposited in the GenBank Database with the following accession numbers: Staphylococcus MZ748472 and Klebsiella MZ748473. We conclude that silver nanoparticles biosynthesized by L. acidophilus are environmentally friendly and have antibacterial activities against MDR pathogenic bacteria.

Designing of fragment based inhibitors with improved activity against E. coli AmpC β-lactamase compared to the conventional antibiotics

One of the most common primary resistance mechanism of multi-drug resistant (MDR) Gram negative pathogenic bacteria to combat β-lactam antibiotics, such as penicillins, cephalosporins and carbapenems is the generation of β- lactamases. The uropathogenic E. coli is mostly getting multi-drug resistance due to the synthesis of AmpC β-lactamases and therefore new antibiotics and inhibitors are needed to treat the evolving infections. The current study was designed for targetting AmpC β-lactamase of E. coli using molecular docking based virtual screening, linking fragments for designing novel compounds and binding mode analysis using molecular dynamic simulation with target protein. The FCH group all-purpose fragment library consisting of 9388 fragments has been screened against AmpC β-lactamase protein of E. coli and the antibiotics and anti-infectives used in treatment of Urinary tract Infections (UTIs) were also screened with AmpC β-lactamase protein. Among the 9388 fragments, 339 fragment candidates were selected and linked with cefepime antibiotic having maximum binding affinity for AmpC target protein. Computational analysis of interactions as well as molecular dynamics (MD) simulations were also conducted for identifying the most promising ligand-pocket complexes from docking investigations to comprehend their thermodynamic properties and verify the docking outcomes as well. Overall, the linked complexes (LCs) showed good binding interactions with AmpC β-lactamase. Interestingly, our fragment-based LCs remained relatively stable in comparison with cefepime antibiotic. Moreover, S12 fragment linked complex remained the most stable during 50 ns with remarkable number of interactions indicating it as promising candidate in novel lead discovery against MDR E. coli infections.

Green synthesis of biocompatible Fe3O4 magnetic nanoparticles using Citrus Sinensis peels extract for their biological activities and magnetic-hyperthermia applications

Green synthesis of nanoparticles (NPs) is eco-friendly, biocompatible, cost-effective, and highly stable. In the present study, Citrus sinensis peel extract was utilized to the fabrication of superparamagnetic iron oxide nanoparticles (SPIONs). The fabricated SPIONs were first characterized using UV–Visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). The UV–Vis spectra analysis displayed a peak at 259 nm due to the surface plasmon resonance. The FTIR spectrum showed bands at 3306 cm−1, and 1616 cm−1 revealed the protein’s involvement in the development and capping of NPs. TEM analysis indicated that green synthesized SPIONs were spherical in shape with particle size of 20–24 nm. Magnetization measurements indicate that the synthesized SPIONs exhibited superparamagnetic behavior at room temperature. The antimicrobial activity, minimum inhibitory concentration (MIC), antioxidant potential, anti-inflammatory effect, and catalytic degradation of methylene blue by SPIONs were investigated in this study. Results demonstrated that SPIONs had variable antimicrobial effect against different pathogenic multi-drug resistant bacteria. At the highest concentration (400 μg/mL), SPIONs showed inhibition zones (14.7–37.3 mm) against all the target isolates. Furthermore, the MIC of synthesized SPIONs against Staphylococcus aureus, Streptococcus mutans, Bacillus subtilis, Escherichia coli, Klebsiella pneumonia, and Candida albicans were 3, 6.5, 6.5, 12.5, 50, 25 μg/mL, respectively. SPIONs exhibited strong antioxidant, anti-inflammatory, and catalytic dye degradation activities. Interestingly, Fe3O4 SPIONs shows optimum magnetic hyperthermia (MHT) techniques under an alternating magnetic field (AMF) measured in specific absorption rate (SAR) of 164, 230, and 286 W/g at concentrations 1, 5, and 10 mg/mL, respectively. Additionally, these newly fabricated SPIONs virtually achieve significant execution under the AMF in fluid MHT and are suitable for biomedical applications.

Evaluation of Antibacterial Activity against Nosocomial Pathogens of an Enzymatically Derived α-Aminophosphonates Possessing Coumarin Scaffold.

The purpose of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and α-amino dimethyl phosphonate moieties, on antimicrobial activity against selected strains of multidrug-resistant nosocomial pathogenic bacteria. The previously developed enzyme-catalysed Kabachnik-Fields protocol allowed us to obtain the studied compounds with high yields which were free from metal impurities. The structure-activity relationship revealed that inhibitory activity is strongly related to the presence of the trifluoromethyl group (CF3-) in the coumarin scaffold. MIC and MBC studies carried out on six selected pathogenic bacterial strains (Gram-positive pathogenic Staphylococcus aureus (ATCC 23235) strain, as well as on Gram-negative Acinetobacter baumannii (ATCC 17978), Pseudomonas aeruginosa (ATCC 15442), Enterobacter cloacae (ATCC 49141), Porphyromonas gingivalis (ATCC 33277), and Treponema denticola (ATCC 35405)) have shown that tested compounds show a strong bactericidal effect at low concentrations. Among all agents investigated, five exhibit higher antimicrobial activity than those observed for commonly used antibiotics. It should be noted that all the compounds tested showed very high activity against S. aureus, which is the main source of nosocomial infections that cause numerous fatalities. Furthermore, we have shown that the studied coumarin-based α-aminophosphonates, depending on their structural characteristics, are non-selective and act efficiently against various Gram-positive and Gram-negative pathogens, which is of great importance for hospitalised patients.

Rational design of Abhisin-like peptides enables generation of potent antimicrobial activity against pathogens.

Infections caused by pathogens can be a significant challenge in wound healing, particularly when antimicrobial resistance is a factor. This can pose a serious threat to human health and well-being. In this scenario, it is imperative to explore novel antimicrobial agents to fight against multi-drug resistant (MDR) pathogenic bacteria. This study employed rational design strategies, including truncation, amino acid replacement, and heterozygosity, to obtain seven α-helical, cationic, and engineered peptides based on the original template of Abhisin. Among the analogs of Abhisin, AB7 displayed broad-spectrum and potent antimicrobial activity, superior targeting of membranes and DNA, and the ability to disrupt biofilms and anti-endotoxins in vitro. Additionally, we evaluated the anti-infection ability of AB7 using a murine skin wound model infected with methicillin-resistant Staphylococcus aureus (MRSA) and found that AB7 displayed negligible toxicity both in vitro and in vivo. Furthermore, AB7 exhibited desirable therapeutic efficacy by reducing bacterial burden and pro-inflammatory mediators, modulating cytokines, promoting wound healing, and enhancing angiogenesis. These results highlight the potential of AB7 as a promising candidate for a new antibiotic. KEY POINTS: • A α-helical, cationic, and engineered peptide AB7 was obtained based on Abhisin. • AB7 exhibited potent antimicrobial activity and multiple bactericidal actions. • AB7 effectively treated infected skin wounds in mice.

Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria.

Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy.

Structural conservation of antibiotic interaction with ribosomes.

The ribosome is a major target for clinically used antibiotics, but multidrug resistant pathogenic bacteria are making our current arsenal of antimicrobials obsolete. Here we present cryo-electron-microscopy structures of 17 distinct compounds from six different antibiotic classes bound to the bacterial ribosome at resolutions ranging from 1.6 to 2.2 Å. The improved resolution enables a precise description of antibiotic-ribosome interactions, encompassing solvent networks that mediate multiple additional interactions between the drugs and their target. Our results reveal a high structural conservation in the binding mode between antibiotics with the same scaffold, including ordered water molecules. Water molecules are visualized within the antibiotic binding sites that are preordered, become ordered in the presence of the drug and that are physically displaced on drug binding. Insight into RNA-ligand interactions will facilitate development of new antimicrobial agents, as well as other RNA-targeting therapies.

Multifactorial Analysis of Biliary Infection in Patients with Hepato-pancreatico-biliary and Associated Intraabdominal Malignancies Admitted to a Teaching Hospital in Northern India.

Blockage of the biliary tract is commonly caused by malignant tumors leading to deranged liver function, responsible for poor prognosis and a high rate of bacteriobilia leading to mortality. We collected retrospective data from the hospital information system and laboratory registers in our department from 2021 to 2022 to evaluate biliary infections in patients with hepato-pancreatico-biliary and associated intraabdominal malignancies. A total of 118 (118/234, 50.43%) patients' bile samples were estimated in this study. Patients' average age was 53.02 ± 13.49 years, with more patients below the age of 65 years among those with infected bile samples. Eight patients were infected by 102 pathogenic microorganisms. The most common pathogenic microorganism responsible for biliary infection in patients with abdominal malignancies was Escherichia coli (38/102, 37.25%) followed by Klebsiella pneumoniae (21/102, 20.59%) and Enterococcus spp. (18/102, 17.65%). Underlying comorbidities like diabetes mellitus, hypothyroidism, hypoproteinemia, chronic liver disease, immunosuppression, chronic kidney disease, increased hospital stay, admission to the intensive care unit (ICU), and presence of percutaneous transhepatic biliary drain were statistically significant risk factors for isolation of multidrug-resistant pathogenic bacteria. Our study guided physicians in identifying the associated demographic characteristics, risk factors, and the spectrum of pathogens responsible for bacteriobilia in abdominal cancer patients along with the antibiotic resistance pattern among these isolates and better selection of antibiotics and antibiotic prophylaxis for patients at risk of developing biliary tract infections with multidrug-resistant pathogens. Kar M, Dubey A, Patel SS, et al. Multifactorial Analysis of Biliary Infection in Patients with Hepato-pancreatico-biliary and Associated Intraabdominal Malignancies Admitted to a Teaching Hospital in Northern India. Euroasian J Hepato-Gastroenterol 2023;13(1):10-17.

Anticancer and antibacterial activity against clinical pathogenic multi-drug resistant bacteria using biosynthesized silver nanoparticles with Mentha pulegium and Crocus caspius extracts

Anticancer and antibacterial activity against clinical pathogenic multi-drug resistant bacteria using biosynthesized silver nanoparticles with Mentha pulegium and Crocus caspius extracts

Antimicrobial activity of essential oils of Curcuma longa and Syzygium aromaticum against multiple drug-resistant pathogenic bacteria.

The present study was conducted to investigate the antimicrobial potential of essential oils of Curcuma longa and Syzygium aromaticum against multidrug-resistant pathogenic bacteria. Four identified bacterial isolates including Methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii were selected and their antibiotic sensitivity was checked by disc diffusion assay. C. longa and S. aromaticum were subjected to steam distillation to obtain their essential oils. The crude essential oils were fractioned by employing column chromatography. Crude essential oils and their fractions were evaluated for their antibacterial activity by agar well diffusion assay and minimum inhibitory concentrations were calculated. All the selected bacterial isolates showed resistance to three or more than three antibiotic groups and were declared as multidrugresistant (MDRs). Crude essential oils of C. longa and S. aromaticum exhibited antimicrobial activity against all selected isolates but S. aromaticum activity was better than the C. longa with a maximum 19.3±1.50 mm zone of inhibition against A. baumannii at 1.04 µL/mL MIC. GC/MS analysis revealed the abundance of components including eugenol, eugenyl acetate, b- caryophyllene, and a- Humulene in both crude oil and fractions of S. aromaticum. While the main components of C. longa essential oil were Ar-tumerone, a-tumerone, b- Tumerone, I-Phellandrene, a-zingibirene, b- sesquiphellandrene, and p- Cymene. This study highlights that plant-based essential oils could be a promising alternative to antibiotics for which pathogens have developed resistance. C. longa and S. aromaticum carry compounds that have antimicrobial potential against multiple drug-resistant bacteria including MRSA. E. coli, K. pneumoniae and A. baumannii.