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Synergistic effects of CuO/TiO2 -chitosan-farnesol nanocomposites: Synthesis, characterization, antimicrobial, and anticancer activities on melanoma cells SK-MEL-3

Indumathi T, Suriyaprakash J, Alarfaj AA, Hirad AH, Jaganathan R, Mathanmohun M

J Basic Microbiol, 2024 Feb;64(2):e2300505.
PMID: 37988658 DOI: 10.1002/jobm.202300505

The current investigation focuses on synthesizing copper oxide (CuO)-titanium oxide (TiO2 )-chitosan-farnesol nanocomposites with potential antibacterial, antifungal, and anticancer properties against Melanoma cells (melanoma cells [SK-MEL-3]). The nanocomposites were synthesized using the standard acetic acid method and subsequently characterized using an X-ray diffractometer, scanning electron microscope, transmission electron microscopy, and Fourier transform infrared spectroscopy. The results from the antibacterial tests against Streptococcus pneumoniae and Stapylococcus aureus demonstrated significant antibacterial efficacy. Additionally, the antifungal studies using Candida albicans through the agar diffusion method displayed a considerable antifungal effect. For evaluating the anticancer activity, various assays such as MTT assay, acridine orange/ethidium bromide dual staining assay, reactive oxygen species (ROS) generation assay, and mitochondrial membrane potential (MMP) analysis were conducted on SK-MEL-3 cells. The nanocomposites exhibited the ability to induce ROS generation, decrease MMP levels, and trigger apoptosis in SK-MEL-3 cells. Collectively, the findings demonstrated a distinct pattern for the synthesized bimetallic nanocomposites. Furthermore, these nanocomposites also displayed significant (p

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Epidemiology of multidrug-resistant Klebsiella pneumoniae infection in clinical setting in South-Eastern Asia: a systematic review and meta-analysis

Salawudeen A, Raji YE, Jibo GG, Desa MNM, Neoh HM, Masri SN, et al.

Antimicrob Resist Infect Control, 2023 Dec 07;12(1):142.
PMID: 38062531 DOI: 10.1186/s13756-023-01346-5

The rising prevalence of multidrug-resistant (MDR) and extended-spectrum beta lactamase-resistant (ESBL) Klebsiella pneumoniae (K. pneumoniae) is an important global public health challenge. This threat is even more pertinent in clinical settings. Morbidity and mortality associated with this condition are alarming particularly in the developing regions of the world. A comprehensive evaluation of the epidemiology of this phenomenon will assist towards the global effort of reducing its burden. So, this systematic review and meta-analysis was conducted to evaluate the epidemiology of MDR K. pneumoniae in South-Eastern Asia (SEA). The study was done under the PRISMA guidelines and was preceded by the development of a priori protocol. The protocol was then registered in PROSPERO-the public registry for systematic reviews. Seven important outcomes which include the assessment of the overall MDR K. pneumoniae prevalence were designed to be evaluated. A literature search was carried out in five selected electronic databases and 4389 were screened. Of these articles, 21 studies that met the eligibility criteria were included in the review. Relevant data were extracted from the included studies. By conducting a quality effect meta-analysis, the pooled prevalence for MDR and ESBL K. pneumoniae in SEA was estimated at 55% (CI 9-96) and 27% (CI 32-100) respectively. The review also identified ESBL genes types of allodemic situations occurring mostly in respiratory tract infections. The high prevalence of MDR and ESBL K. pneumoniae in this subregion is highly significant and of both public health and clinical relevance. Overall, the findings of this review will assist in the effective prevention and control of this threat in SEA.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
Elucidating the structural, catalytic, and antibacterial traits of Ficus carica and Azadirachta indica leaf extract-mediated synthesis of the Ag/CuO/rGO nanocomposite

Fayyaz Z, Farrukh MA, Ul-Hamid A, Chong KK

Microsc Res Tech, 2024 May;87(5):957-976.
PMID: 38174385 DOI: 10.1002/jemt.24487

The present exploration demonstrates the efficient, sustainable, cost-effective, and environment-friendly green approach for the synthesis of silver (Ag)-doped copper oxide (CuO) embedded with reduced graphene oxide (rGO) nanocomposite using the green one-pot method and the green deposition method. Leaf extracts of Ficus carica and Azadirachta indica were used for both methods as reducing and capping agents. The effect of methodology and plant extract was analyzed through different characterization techniques such as UV-visible spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM). The lowest band gap of 3.0 eV was observed for the Ag/CuO/rGO prepared by the green one-pot method using F. carica. The reduction of graphene oxide (GO) and the formation of metal oxide was confirmed through functional group detection using FT-IR. Calculation of thermodynamic parameters showed that all reactions involved were nonspontaneous and endothermic which shows the stability of nanocomposites. XRD studies revealed the crystallinity, phase purity and small average crystallite size of 32.67 nm. SEM images disclosed that the morphology of the nanocomposites was spherical with agglomeration and rough texture. The particle size of the nanocomposites calculated through HRTEM was found in agreement with the XRD results. The numerous properties of the synthesized nanocomposites enhanced their potential against the degradation of methylene blue, rhodamine B, and ciprofloxacin. The highest percentage degradation of Ag/CuO/rGO was found to be 97%, synthesized using the green one-pot method with F. carica against ciprofloxacin, which might be due to the lowest band gap, delayed electron-hole pair recombination, and large surface area available. The nanocomposites were also tested against the Gram-positive and Gram-negative bacteria. RESEARCH HIGHLIGHTS: Facile synthesis of Ag/CuO/rGO nanocomposite using a green one-pot method and the green deposition method. The lowest band gap of 3.0 eV was observed for nanocomposite prepared by a green one-pot method using Ficus carica. Least average crystallite size of 32.67 nm was found for nanocomposite prepared by a green one-pot method using F. carica. Highest antibacterial and catalytic activity (97%) was obtained against ciprofloxacin with nanocomposite prepared through green one-pot method using F. carica. A mechanism of green synthesis is proposed.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Fulltext Optimisation of preparation conditions for Ti nanowires and suitability as an antibacterial material

Munisparan T, Yang ECY, Paramasivam R, Dahlan NA, Pushpamalar J

IET Nanobiotechnol, 2018 Jun;12(4):429-435.
PMID: 29768225 DOI: 10.1049/iet-nbt.2017.0186

Ultrafine titanium dioxide (TiO2) nanowires were synthesised using a hydrothermal method with different volumes of ethylene glycol (EG) and annealing temperatures. It shows that sodium titanate nanowires synthesised using 5 and 10 ml EG, which annealed at 400°C produced TiO2 nanowires that correspond to a photochemically active phase, which is anatase. The influences of annealing temperatures (400-600°C) on the morphological arrangement of TiO2 nanowires were evident in the field emission scanning electron microscopy. The annealing temperature of 500°C led to agglomeration, which formed a mixture of TiO2 nanoparticles and nanowires. High thermal stability of TiO2 nanowires revealed by thermogravimetric analysis and Fourier transform infrared spectroscopy spectrum showed the presence of the Ti-O-Ti vibrations as evidenced due to TiO2 lattices. An antibacterial study using TiO2 nanowires toward Escherichia coli and Klebsiella pneumoniae showed large zones of inhibition that indicated susceptibility of the microbe toward TiO2. Growth kinetic analysis shows that addition of TiO2 has reduced optical density (OD) suggesting an inhibition of the growth of bacteria. These results indicate TiO2 nanowires can be effectively used as an antimicrobial agent against gram-bacteria. The TiO2 nanowires could be exploited in the medical, packaging and detergent formulation industries and wastewater treatment.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry*
Synthesis and characterization of marine seagrass (Cymodocea serrulata) mediated titanium dioxide nanoparticles for antibacterial, antibiofilm and antioxidant properties

Narayanan M, Srinivasan S, Gnanasekaran C, Ramachandran G, Chelliah CK, Rajivgandhi G, et al.

Microb Pathog, 2024 Apr;189:106595.
PMID: 38387848 DOI: 10.1016/j.micpath.2024.106595

Cymodocea serrulata mediated titanium dioxide nanoparticles (TiO2 NPs) were successfully synthesized. The XRD pattern and FTIR spectra demonstrated the crystalline structure of TiO2 NPs and the presence of phenols, flavonoids and alkaloids in the extract. Further SEM revealed that TiO2 NPs has uniform structure and spherical in shape with their size ranged from 58 to 117 nm. Antibacterial activity of TiO2 NPs against methicillin-resistant Staphylococcus aureus (MRSA) and Vibrio cholerae (V. cholerae), provided the zone of inhibition of 33.9 ± 1.7 and 36.3 ± 1.9 mm, respectively at 100 μg/mL concentration. MIC of TiO2 NPs against MRSA and V. cholerae showed 84% and 87% inhibition at 180 μg/mL and 160 μg/mL respectively. Subsequently, the sub-MIC of V. cholerae demonstrated minimal or no impact on bacterial growth at concentration of 42.5 μg/mL concentration. In addition, TiO2 NPs exhibited their ability to inhibit the biofilm forming V. cholerae which caused distinct morphological and intercellular damages analysed using CLSM and TEM. The antioxidant properties of TiO2 NPs were demonstrated through TAA and DPPH assays and exposed its scavenging activity with IC50 value of 36.42 and 68.85 μg/mL which denotes its valuable antioxidant properties with potential health benefits. Importantly, the brine shrimp based lethality experiment yielded a low cytotoxic effect with 13% mortality at 100 μg/mL. In conclusion, the multifaceted attributes of C. serrulata mediated TiO2 NPs encompassed the antibacterial, antioxidant and anti-biofilm inhibition effects with low cytotoxicity in nature were highlighted in this study and proved the bioderived TiO2 NPs could be used as a promising agent for biomedical applications.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Fulltext Carbon nanodots as molecular scaffolds for development of antimicrobial agents

Ngu-Schwemlein M, Chin SF, Hileman R, Drozdowski C, Upchurch C, Hargrove A

Bioorg Med Chem Lett, 2016 Apr 01;26(7):1745-9.
PMID: 26923697 DOI: 10.1016/j.bmcl.2016.02.047

We report the potential of carbon nanodots (CNDs) as a molecular scaffold for enhancing the antimicrobial activities of small dendritic poly(amidoamines) (PAMAM). Carbon nanodots prepared from sago starch are readily functionalized with PAMAM by using N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Electron microscopy images of these polyaminated CNDs show that they are approximately 30-60nm in diameter. Infrared and fluorescence spectroscopy analyses of the water-soluble material established the presence of the polyamidoaminated moiety and the intrinsic fluorescence of the nanodots. The polyaminated nanodots (CND-PAM1 and CND-PAM2) exhibit in vitro antimicrobial properties, not only to non-multidrug resistant bacteria but also to the corresponding Gram-negative multidrug bacteria. Their minimum inhibitory concentration (MIC) ranges from 8 to 64μg/mL, which is much lower than that of PAMAM G1 or the non-active PAMAM G0 and CNDs. Additionally, they show synergistic effect in combination with tetracycline or colistin. These preliminary results imply that CNDs can serve as a promising scaffold for facilitating the rational design of antimicrobial materials for combating the ever-increasing threat of antibiotic resistance. Moreover, their fluorescence could be pertinent to unraveling their mode of action for imaging or diagnostic applications.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*; Anti-Bacterial Agents/chemistry*
In vitro antibacterial activity and physicochemical properties of a crude methanol extract of the larvae of the blow fly Lucilia cuprina

Teh CH, Nazni WA, Lee HL, Fairuz A, Tan SB, Sofian-Azirun M

Med Vet Entomol, 2013 Dec;27(4):414-20.
PMID: 23650928 DOI: 10.1111/mve.12012

The emergence of multidrug-resistant bacterial strains has prompted the reintroduction of maggot therapy in the treatment of chronic, infected wounds. Many previous studies have demonstrated the potent antibacterial activity of larval excretions/secretions of the blowfly Lucilia sericata (Meigen) (Diptera:Calliphoridae) against bacteria. However, the antibacterial activity of its sibling species, Lucilia cuprina (Wiedemann) (Diptera:Calliphoridae) against a wide range of pathogenic bacteria has never been determined. The aim of this study was to develop a new procedure to produce whole body extract of larvae of L. cuprina via methanol extraction as well as to demonstrate the in vitro antibacterial activity of this extract against seven selected wound pathogens (Staphylococcus aureus, methicillin-resistant S. aureus, S. epidermidis, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli). The turbidimetric assay demonstrated that L. cuprina larval extract was significantly potent against all bacteria tested (P

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*; Anti-Bacterial Agents/chemistry
Phyto-fabricated ZnO nanoparticles for anticancer, photo-antimicrobial effect on carbapenem-resistant/sensitive Pseudomonas aeruginosa and removal of tetracycline

Venkatraman G, Mohan PS, Mashghan MM, Wong KC, Abdul-Rahman PS, Vellasamy KM, et al.

Bioprocess Biosyst Eng, 2024 Aug;47(8):1163-1182.
PMID: 38491194 DOI: 10.1007/s00449-024-02984-8

Alternanthera sessilis (AS) leaf extract was used to synthesize zinc oxide nanoparticles (ZnO NPs). Bioanalytical characterization techniques such as X-ray diffraction (XRD) and field emission scanning electron microscope (FESEM) confirmed the formation of crystalline ZnO NPs with average sizes of 40 nm. The AS-ZnO NPs antimicrobial activity was analyzed under dark (D) and white light (WL) conditions. The improved antimicrobial activity was observed against Escherichia coli, Staphylococcus aureus and Bacillus subtilis at the minimal inhibitory concentration (MIC) of 125 and 62.5 µg/mL under WL than the D at 125 and 250 µg/mL for E. coli, B. subtilis, and Pseudomonas aeruginosa, respectively. In contrast, the growth of P. aeruginosa and S. aureus was not completely inhibited until 1 mg/mL AS-ZnO NPs under WL and D. Similarly, AS-ZnO NPs displayed a weaker inhibitory effect against carbapenem-sensitive P. aeruginosa (CSPA) and carbapenem-resistant P. aeruginosa (CRPA) strains of PAC023, PAC041 and PAC032, PAC045 under D. Interestingly, the distinct inhibitory effect was recorded against CSPA PAC041 and CRPA PAC032 in which the bacteria growth was inhibited 99.9% at 250, 500 µg/mL under WL. The cytotoxicity results suggested AS-ZnO NPs demonstrated higher toxicity to MCF-7 breast cancer cells than the RAW264.7 macrophage cells. Further, AS-ZnO NPs exhibited higher catalytic potential against tetracycline hydrochloride (TC-H) degradation at 65.6% and 60.8% under WL than the dark at 59.35% and 48.6% within 120 min. Therefore, AS-ZnO NPs can be used to design a photo-improved antimicrobial formulation and environmental catalyst for removing TC-H from wastewater.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Fulltext Designing mRNA- and Peptide-Based Vaccine Construct against Emerging Multidrug-Resistant Citrobacter freundii: A Computational-Based Subtractive Proteomics Approach

Naveed M, Hassan JU, Ahmad M, Naeem N, Mughal MS, Rabaan AA, et al.

Medicina (Kaunas), 2022 Sep 27;58(10).
PMID: 36295517 DOI: 10.3390/medicina58101356

Background and Objectives: Citrobacter freundii (C. freundii) is an emerging and opportunistic Gram-negative bacteria of the human gastrointestinal tract associated with nosocomial and severe respiratory tract infections. It has also been associated with pneumonia, bloodstream, and urinary tract infections. Intrinsic and adaptive virulence characteristics of C. freundii have become a significant source of diarrheal infections and food poisoning among immune-compromised patients and newborns. Impulsive usage of antibiotics and these adaptive virulence characteristics has modulated the C. freundii into multidrug-resistant (MDR) bacteria. Conventional approaches are futile against MDR C. freundii. Materials and Methods: The current study exploits the modern computational-based vaccine design approach to treat infections related to MDR C. freundii. A whole proteome of C. freundii (strain: CWH001) was retrieved to screen pathogenic and nonhomologous proteins. Six proteins were shortlisted for the selection of putative epitopes for vaccine construct. Highly antigenic, nonallergen, and nontoxic eleven B-cell, HTL, and TCL epitopes were selected for mRNA- and peptide-based multi-epitope vaccine construct. Secondary and tertiary structures of the multi-epitope vaccine (MEVC) were designed, refined, and validated. Results: Evaluation of population coverage of MHC-I and MHC-II alleles were 72% and 90%, respectively. Docking MEVC with TLR-3 receptor with the binding affinity of 21.46 (kcal/mol) occurred through the mmGBSA process. Further validations include codon optimization with an enhanced CAI value of 0.95 and GC content of about 51%. Immune stimulation and molecular dynamic simulation ensure the antibody production upon antigen interaction with the host and stability of the MEVC construct, respectively. Conclusions: These interpretations propose a new strategy to combat MDR C. freundii. Further, in vivo and in vitro trials of this vaccine will be valuable in combating MDR pathogens.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
Fulltext Preparation, Characterization and Biological Activities of an Oil-in-Water Nanoemulsion from Fish By-Products and Lemon Oil by Ultrasonication Method

Azmi NAN, Elgharbawy AAM, Salleh HM, Moniruzzaman M

Molecules, 2022 Oct 09;27(19).
PMID: 36235261 DOI: 10.3390/molecules27196725

Fish by-product oil and lemon oil have potential applications as active ingredients in many industries, including cosmetics, pharmaceuticals and food. However, the physicochemical properties, especially the poor stability, compromised the usage. Generally, nanoemulsions were used as an approach to stabilize the oils. This study employed an ultrasonication method to form oil-in-water nanoemulsion of lemon and fish by-product oils (NE-FLO). The formulation is produced at a fixed amount of 2 wt% fish by-product oil, 8 wt% lemon oil, 10 wt% surfactant, 27.7 wt% co-surfactants and 42 min of ultrasonication time. The size, polydispersity index (PDI) and zeta potential obtained were 44.40 nm, 0.077, and -5.02 mV, respectively. The biological properties, including antioxidant, antibacterial, cell cytotoxicity, and anti-inflammatory, showed outstanding performance. The antioxidant activity is comparable without any significant difference with ascorbic acid as standard and is superior to pure lemon oil. NE-FLO successfully inhibits seven Gram-positive and seven Gram-negative bacterial strains. NE-FLO's anti-inflammatory activity is 99.72%, comparable to nordihydroguaiaretic acid (NDGA) as the standard. At a high concentration of 10,000 µg·mL-1, NE-FLO is non-toxic to normal skin cells. These findings demonstrate that the NE-FLO produced in this study has significant potential for usage in various industries.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Fulltext Pharmacotherapeutics Applications and Chemistry of Chalcone Derivatives

Dhaliwal JS, Moshawih S, Goh KW, Loy MJ, Hossain MS, Hermansyah A, et al.

Molecules, 2022 Oct 19;27(20).
PMID: 36296655 DOI: 10.3390/molecules27207062

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,β-unsaturated system in the chalcone's rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Risk factor for inappropriate use of prophylactic antibiotics in inguinal hernia repair surgery

Hendrawan F, Nugrahningsih DAA, Purnomo E, Azdy NA

Med J Malaysia, 2024 Aug;79(Suppl 4):58-62.
PMID: 39215416

INTRODUCTION: There are some complications that can arise after surgery, like surgical site infection (SSI). In hernia repair, SSI incidence is low. Hence, the clinical practice guideline (CPG) published by the HerniaSurge Group (THG) does not recommend prophylactic antibiotics for hernia repair. Despite the unnecessary use of prophylactic antibiotics, regarding patient safety, prophylactic antibiotics can be used. However, each hospital has its own CPG and recommended antimicrobials based on the infection cases in its site. Regarding antimicrobial resistances, evaluating prophylactic antibiotics is essential to prevent increasing incidence of antimicrobial resistance cases. The aim of this study is to evaluate the use of prophylactic antibiotics in hernia inguinal cases.
MATERIALS AND METHODS: This cross-sectional analytic study used patients' medical records between 2015 to 2020. Demographic data, surgery data and the used antimicrobial data were extracted and written in case report form. Identification of risk factors for inappropriate use of prophylactic antibiotics was done using logistic regression.
RESULTS: We identified 55 inappropriate times of preoperative prophylactic antibiotic therapy cases out of 80 cases and 63 cases in post-operative antibiotics were different from the guideline. Statistical analysis did not find any factor related to inappropriate therapy time.
CONCLUSION: The misuse of prophylactic antibiotics was frequently found regarding the duration of prophylactic antibiotics in both pre- and post-surgery setting. Nonetheless, no risk factor was identified with the inappropriate use of prophylactic antibiotics.

Matched MeSH terms: Anti-Bacterial Agents/administration & dosage; Anti-Bacterial Agents/therapeutic use
Enhancing refrigerated chicken breasts preservation: Novel composite hydrogels incorporated with antimicrobial peptides, bacterial cellulose, and polyvinyl alcohol

Si S, Huang X, Wang Q, Manickam S, Zhao D, Liu Y

Int J Biol Macromol, 2024 Nov;281(Pt 4):136505.
PMID: 39395516 DOI: 10.1016/j.ijbiomac.2024.136505

Microbial contamination annually leads to substantial food resource loss. Effective food packaging can mitigate food contamination and waste, yet conventional materials such as plastics often lack bacteriostatic activity. This study aimed to synthesise FengycinA-M3@bacterial cellulose@polyvinyl alcohol composite hydrogels via dual cross-linking with hydrogen and borate bonding, with the goal of enhancing antibacterial properties and prolonging the preservation period of refrigerated chicken breast. The composite hydrogel was subjected to comprehensive characterisation for structural, mechanical, water absorption, slow peptide release, antimicrobial capacity, biocompatibility, and chicken breast freshness preservation. The results showed that the composite hydrogel had a porous network structure and excellent gel elasticity and biocompatibility. It was effective in inhibiting Staphylococcus aureus and Escherichia coli, and prolonged the storage time of frozen chicken breast for up to 12 days. These findings emphasise the potential of hydrogel food packaging to prolong storage periods and its suitability for food industry applications due to ease of manufacture.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Designing potential lead compounds targeting aminoglycoside N (6')-acetyltransferase in Serratia marcescens: A drug discovery strategy

Prabhu D, Shankari G, Rajamanikandan S, Jeyakanthan J, Velusamy P, Gopinath SCB, et al.

Int J Biol Macromol, 2024 Nov;281(Pt 1):136976.
PMID: 39490491 DOI: 10.1016/j.ijbiomac.2024.136976

Serratia marcescens is an opportunistic human pathogen that causes urinary tract infections, ocular lens infections, and respiratory tract infections. S. marcescens employs various defense mechanisms to evade antibiotics, one of which is mediated by aminoglycoside N-acetyltransferase (AAC). In this mechanism, the enzyme AAC facilitates the transfer and linkage of the acetyl moiety from the donor substrate acetyl-coenzyme A to specific positions on antibiotics. This modification alters the antibiotic's structure, leading to the inactivation of aminoglycoside antibiotics. In the current scenario, antibiotic resistance has become a global threat, and targeting the enzymes that mediate resistance is considered crucial to combat this issue. The study aimed to address the increasing global threat of antibiotic resistance in Serratia marcescens by targeting the aminoglycoside N-acetyltransferase (AAC (6')) enzyme, which inactivates aminoglycoside antibiotics through acetylation. Due to the absence of experimental structure, we constructed a homology model of aminoglycoside N (6')-acetyltransferase (AAC (6')) of S. marcescens using the atomic structure of aminoglycoside N-acetyltransferase AAC (6')-Ib (PDB ID: 1V0C) as a template. The stable architecture and integrity of the modelled AAC (6') structure were analyzed through a 100 ns simulation. Structure-guided high-throughput screening of four small molecule databases (Binding, Life Chemicals, Zinc, and Toslab) resulted in the identification of potent inhibitors against AAC (6'). The hits obtained from screening were manually clustered, and the five hit molecules were shortlisted based on the docking score, which are observed in the range of -17.09 kcal/mol to -11.95 kcal/mol. These selected five molecules displayed acceptable pharmacological properties in ADME predictions. The binding free energy calculations, and molecular dynamics simulations of ligand bound AAC (6') complexes represented higher affinity and stable binding. The selected molecules demonstrated stable binding with AAC (6'), indicating their strong potential to hamper the binding of aminoglycoside in the respective site. and thereby inhibit. This process mitigates enzyme mediated AAC (6') activity on aminoglycosides and reverse the bactericidal function of aminoglycosides, and also this method could serve as a platform for the development of potential antimicrobials.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
How Important is the Metal-free Catalytic Knoevenagel Reaction in Medicinal Chemistry? An Updated Review

Johari S, Johan MR, Khaligh NG

Curr Med Chem, 2024;31(27):4286-4311.
PMID: 38243980 DOI: 10.2174/0109298673260463231122074253

The Knoevenagel condensation is a powerful and primary step for the development of carbon-carbon bond transformations. These condensations offer versatile products/ intermediates for diverse uses in polymers, cosmetics, chemical industries, and medicinal chemistry. Various homogenous and heterogenous catalysts have been found to promote the Knoevenagel condensation reaction, both environmentally and economically. Due to their attractive use in the production of pharmaceutical drugs, they are proven to be the main force that drives the synthesis involving numerous multi-component and multistep reactions. The present study, therefore, aims to summarise reported Knoevenagel condensation reactions using metal-free catalysts resulting in pharmaceutically useful compounds with anti-cancer, anti-tumor, anti-oxidant, anti-malarial, anti-diabetic, and anti- bacterial activities. By considering factors like their structure-activity relationships (SARs), the reaction conditions, and the steps involved, as well as the advantages and limitations of the particular approach, we also provide a general framework and direction in order to achieve superior characteristics of the catalyst.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Fulltext Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis

Alhajj N, Yahya MFZR, O'Reilly NJ, Cathcart H

Eur J Pharm Sci, 2024 Jan 01;192:106654.
PMID: 38013123 DOI: 10.1016/j.ejps.2023.106654

Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED ∼ 71 %; FPF ∼ 49 %) compared to formulations containing MAN and NAC (ED ∼ 64 % and 44 %; FPF ∼ 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
Evaluation of antibacterial, antifungal and antibiofilm activities of A. baumannii-derived tannase and gallic acid against uropathogenic microorganisms

Abdulshaheed AA, Hanafiah MM, Nawaz R, Muslim SN

Microb Pathog, 2024 Feb;187:106534.
PMID: 38184176 DOI: 10.1016/j.micpath.2024.106534

One of the most prevalent infectious diseases and a key driver of antibiotic prescriptions in pediatrics is urinary tract infection (UTI). Due to the emergence of more resistant uropathogenic bacterial and fungal strains, current treatments are no longer effective, necessitating the urgent development of novel antibacterial and antifungal drugs. In this study, the antifungal, antibacterial, and anti-biofilm capabilities of compounds, such as tannase (TN) and gallic acid (GA), which were produced from a novel natural source, Acinetobacter baumannii (AB11) bacteria, were assessed for the inactivation of uropathogenic microorganisms (UMs). Ammonium sulphate precipitation, ion exchange, high-performance liquid chromatography, and gel filtration were used to purify TN and GA that were isolated from A. baumannii. A 43.08 % pure TN with 1221.2 U/mg specific activity and 10.51 mg/mL GA was obtained. The antibacterial, antifungal and anti-biofilm activities of TN and GA were evaluated against UMs and compared to those of commercially available antibiotics including sulfamethoxazole (SXT), levofloxacin (LEV), ciprofloxacin (CIP), amikacin (Ak), and nitrofurantoin (F). The results showed that TN and GA were superior to commercial antibiotics in their ability to inactivate UMs and considerably reduced biofilms formation. Additionally, the GA emerges as the top substitute for currently available medications, demonstrating superior antibacterial and antibiofilm properties against all UMs evaluated in this study. The results of this investigation showed that A. baumannii-derived TN and GA could be utilized as an alternative medication to treat UTIs.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
Antibacterial and Antifouling Properties of the Horseshoe Crab Carcinoscorpius rotundicauda

Mohd Faizal MN, Ismail N, M S Eldeen I, Mariam T

Pak J Biol Sci, 2021 Jan;24(5):579-587.
PMID: 34486333 DOI: 10.3923/pjbs.2021.579.587

Background and Objective: Horseshoe crabs are widely used in both traditional and modern pharmaceutical applications. Most of the previous studies on horseshoe crabs focused on their blood which contains hemolymph and amoebocyte lysate. This study aimed to determine the potential antibacterial and antifouling properties of different extracts from the carapace and the book gills of Carcinoscorpius rotundicauda. Materials and Methods: The crude extracts were subjected to the bioactivity tests using the disc-diffusion and the inhibition of biofilm-formation measurement assays, for both the antibacterial and antifouling activities respectively. Results: The results obtained indicated that the carapace extracts had stronger antibacterial and antifouling effects compared to the book gills extracts. Extracts obtained from the male displayed more activity compared to the extracts from the female with a few exceptions. Methanol and acetone carapace crude extracts showed the best overall performance. A sterol compound was isolated from the carapace acetone extracts of the male of C. rotundicauda. However, the compound did not display strong activity compared to the crude extract. The compound might be contributing to the observed activity with other components through a synergistic effect. Conclusion: The presence of antibacterial and antifouling activities in the carapace and book gills extracts could be added to the complexity of the defence mechanisms of horseshoe crabs. The results of this study, therefore, may contribute to the knowledge of the defence mechanisms of C. rotundicauda. Further research is needed to determine the bioactivities of other parts of the animal and to explore their potential applications.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
Fulltext Assessing the colony morphotypes and antibiotic susceptibility profile of Malaysian clinical Burkholderia pseudomallei to support the use of EUCAST disk diffusion breakpoints to determine antibiotic resistance

Hii SYF, Zaiful Bahrina NN, Mohd Zaidi MN, Hashim R, Ahmad N

Eur J Clin Microbiol Infect Dis, 2024 Feb;43(2):373-378.
PMID: 37999783 DOI: 10.1007/s10096-023-04707-5

Burkholderia pseudomallei is intrinsically resistant to many antibiotics. This study aimed to assess bacterial colony morphotypes and the validity of using disk diffusion method (DD) to determine antibiotic resistance in Malaysian clinical B. pseudomallei isolates for ceftazidime (CAZ), meropenem (MEM), amoxicillin-clavulanate (AMC) and doxycycline (DOX). DD produced good categorical agreements exhibiting concordance of 100% with reference method, broth microdilution for CAZ and DOX, 98.6% for MEM and 97.2% for AMC. Smooth-centred colonies were most frequently observed. EUCAST DD interpretative criterion is suitable to interpret B. pseudomallei CAZ, MEM, AMC and DOX resistance. Increasing AMC MIC in B. pseudomallei is a concern.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
Prevalence and antimicrobial resistance profile of Salmonella typhi infection in Iraq, 2019-2021

Nassir KF, Ali BM, Ibrahim ZH, Qasim ZJ, Mahdi SG, Mustafa NM, et al.

Med J Malaysia, 2024 Jan;79(1):74-79.
PMID: 38287761

INTRODUCTION: Salmonella typhi could infect the intestinal tract and the bloodstream or invade body organs and secrete endotoxins. It is endemic in developing countries. It is increasingly evolving antimicrobial resistance to several commonly used antimicrobial agents.
MATERIALS AND METHODS: A cross-sectional study was done at Iraqi Communicable Disease Control Center, where all confirmed cases of Salmonella typhi are reported, for a period 2019-2021. All demographic, epidemiological and clinical characteristics of patients, comorbidities, type of samples, distribution of S. typhi by age and gender, time distribution in each year and profile of bacterial resistance and sensitivity to antibiotics were gathered and analysed.
RESULTS: Most samples were taken from blood. The mean age of cases during 2019, 2020 and 2021 was 18.7 ± 6.5, 17.7 ± 14.1 and 17.3 ± 12.8. Males constituted 56.7%, 58.5% and 39.8%, respectively. Some cases had comorbidities. Most cases had headache and fever. Some of them had nausea, diarrhoea, vomiting and epigastric pain. The age and sex were significantly associated with years of reporting. The most months of case reporting were June-July (2019 and 2021), Jan. -Feb. (2020). There was an obvious increase in S. typhi resistance to ceftriaxone (92.2%, 86.1%, 88.8%) and ampicillin (77.1%, 76.9%, 81.27%). There was a gradual increase in sensitivity to tetracycline (83.1%, 88.1%, 94%), cotrimoxazole (86.7%, 86.1%, 92.2%), ciprofloxacin (78.3%, 90.1%, 87.8%) and cefixime (77.7%, 72.3%, 72.7%).
CONCLUSIONS: There was a sharp rise in resistance rates of the S. typhi in Iraq (during 2019-2021) to ceftriaxone and ampicillin, while there were highest sensitivity rates to imipenem, aztreonam and chloramphenicol. The following recommendations were made: (1) Improvement of general hygiene and food safety measures. (2) Emphasis on vaccination and surveillance of Salmonella infection. (3) Rational use of appropriate antibiotics through implementation of treatment guidelines. (5) Educate communities and travelers about the risks of S. typhi and its preventive measures.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use

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