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Antimicrobial resistance (AMR) poses a serious threat to human, animal, and plant health on a global scale. Search and elimination techniques should be used to effectively counter the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections. With only a few novel drugs in clinical development, the quest for plant-based alternatives to prevent the spread of antibiotic resistance among bacteria has accelerated. Treatment of MRSA infections is challenging owing to rapidly emerging resistance mechanisms coupled with their protective biofilms. In the present research, we examined the antibacterial properties of ten plant-derived ethanolic leaf extracts. The most effective ethanolic leaf extract against MRSA in decreasing order of zone of inhibition, Cannabis sativa L. > Syzygium cumini > Murraya koenigii > Eucalyptus sp. > while Aloe barbadensis, Azadirachta indica, had very little impact. Mangifera indica, Curcuma longa, Tinospora cordifolia, and Carica papaya did not exhibit inhibitory effects against MRSA; hence, Cannabis was selected for further experimental study. The minimal inhibitory concentration (MIC) of Cannabis sativa L. extract was 0.25 mg ml -1 with 86% mortality. At a sub-MIC dosage of 0.125 mg ml -1 , the biofilm formation was reduced by 71%. The two major cannabinoids detected were cannabidiol and delta-9-tetrahydrocannabinol (Δ9-THC), which were majorly attributed to substantial inhibitory action against MRSA. The time-kill kinetics demonstrated a bactericidal action at 4 MIC over an 8-20-h time window with a 90% reduction in growth rate. The results from SEM, and light microscopy Giemsa staining revealed a reduction in cells in the treated group with increased AKP activity, indicating bacterial cell membrane breakdown. These findings suggested cannabinoids may be a promising alternative to antibiotic therapy for bovine biofilm-associated MRSA., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The mastitis milk sample was collected from LUVAS Uchani in Karnal, Haryana, India, as part of the SERB-funded project “Mastitis related antibiotic resistance pattern mapping in three districts of Haryana (FILENO. EMR/2017/004602)”, which detailed the research aims and methodology. Approval for the study and its protocols, materials, and methods was granted by the Institutional Biosafety Committee (IBSC) of the National Dairy Research Institute (NDRI) in Karnal, India. Consent to participate: No consent was required as no experiments related to humans were performed. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The requirement for accurate treatments for skin diseases and wounds, generated a rising interest towards multifunctional polymer composites, that are capable of mimicking the natural compositions in human body. Also, electroactive composite films disseminate endogenous electrical stimulations that encourage cell migration and its proliferation at wound site, proposing greater opportunities in upgrading the conventional wound patches. In this work, the composite film made of graphene oxide, Ag 2 O, PVA and chitosan were developed for wound healing applications, by the solution casting method. The even dispersibility of nanofiller in polymeric matrix was validated from the physicochemical analyses. The increment in roughness of the composite film surface was noted from AFM images. The thermal stability and porous nature of the polymer composite were also verified. A conductivity value of 0.16 × 10 -4 Scm -1 was obtained for the film. From MTT assay, it was noted that the films were non-cytotoxic and supported cell adhesion along with cell proliferation of macrophage (RAW 264.7) cells. Moreover, the composite film also demonstrated non-hemolytic activity of <2 %, as well as excellent antibacterial activity towards E. coli and S. aureus. Thus, the obtained results validated that the prepared composite film could be chosen as an innovative candidate for developing state-of-the-art wound dressings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

According to the World Health Organization, infectious diseases, particularly those caused by multidrug-resistant bacteria (MDR), are projected to claim the lives of 15 million people by 2050. Septicemia carries a higher morbidity and mortality rate than infections caused by susceptible Pseudomonas aeruginosa, and MDR-mediated ocular infections can lead to impaired vision and blindness. To identify and develop a potential drug against MDR P. aeruginosa, we employed in silico reverse genetics-based target mining, drug prioritization, and evaluation. Rare Lipoprotein A (RlpA) was selected as the target protein, and its crystal structure was geometrically optimized. Molecular docking and virtual screening analyses revealed that RlpA exhibits strong binding affinity with 11 compounds. Among these, 3-chlorophthalic acid was evaluated, and subsequent in vitro assays demonstrated significant anti-Pseudomonas activity with negligible cytotoxicity. The compound was further evaluated against both drug-susceptible and MDR P. aeruginosa strains in vitro, with cytotoxicity assessed using an MTT assay. The study demonstrated that 3-chlorophthalic acid exhibits potent anti-Pseudomonas activity with minimal toxicity to host cells. Consequently, this compound emerges as a promising candidate against MDR P. aeruginosa, warranting further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Micro/nano scale surface modifications of titanium based orthopedic and cardiovascular implants has shown to augment biocompatibility. However, bacterial infection remains a serious concern for implant failure, aggravated by increasing antibiotic resistance and over usage of antibiotics. Bacteria cell adhesion on implant surface leads to colonization and biofilm formation resulting in morbidity and mortality. Hence, there is a need to develop new implant surfaces with high antibacterial properties. Recent developments have shown that superhydrophobic surfaces prevent protein and bacteria cell adhesion. In this study, a thermochemical treatment was used modify the surface properties for high efficacy antibacterial activity on titanium surface. The modification led to a micro-nano surface topography and upon modification with polyethylene glycol (PEG) and silane the surfaces were superhydrophilic and superhydrophobic, respectively. The modified surfaces were characterized for morphology, wettability, chemistry, corrosion resistance and surface charge. The antibacterial capability was characterized with Staphylococcus aureus and Escherichia coli by evaluating the bacteria cell inhibition, adhesion kinetics, and biofilm formation. The results indicated that the superhydrophobic micro-nano structured titanium surface reduced bacteria cell adhesion significantly (>90%) and prevented biofilm formation compared to the unmodified titanium surface after 24 h of incubation., (© 2022 Wiley Periodicals LLC.)

The treatment of Helicobacter pylori usually fails due to their ability to form biofilms and resistance to antibiotics. This might potentially lead to gastric carcinoma and mucosa-associated lymphoid tissue lymphoma. In the present study, we elucidate the potential role of N-acylhomoserine lactonase stabilized silver nanoparticles (AiiA-AgNPs) in treating biofilms produced by H. pylori. AiiA-AgNPs inhibited quorum sensing (QS) by degradation of QS molecules, thereby reducing biofilm formation, urease production, and altering cell surface hydrophobicity of H. pylori. AiiA-AgNPs showed no cytotoxic effects on RAW 264.7 macrophages at the effective concentration (1-5 µM) of antibiofilm activity. In addition, AiiA-AgNP in high concentration (80-100 µM) exhibited cytotoxicity against HCT-15 carcinoma cells, depicting its therapeutic role in treating cancer., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mg-doped zinc oxide (Zn 1-x Mg x O, where x = 0.000, 0.001, 0.003, 0.005, and 0.010 M) nanoparticles (MgZnO NPs) were synthesized via a co-precipitation method and subjected to various analyses for application as functional additives in food packaging. The MgZnO NPs were successfully formed at approximately 360 °C and showed an increase in the optical band gap with respect to the increase in the concentration of Mg doping. The X-ray diffraction and scanning electron microscopy analyses of MgZnO NPs confirmed the formation of hexagonal wurtzite structure and rod-like morphology. X-ray photoelectron spectra revealed that the Mg (1s) peaks centered at 1303.35 and 1303.38 eV were ascribed to the presence of Mg 2+ replacing Zn 2+ . Transmission electron microscopy images showed rod shapes with the length of 208-650nm and width of 84-142 nm. Various concentrations of synthesized MgZnO NPs were investigated against a gram-negative (Escherichia coli - DH5α) bacterial strain under light and dark conditions. Among the studied samples, 0.010 M MgZnO NPs of concentration 3 mg/mL showed the best antibacterial activity under the light condition. MgZnO NPs revealed uneven ridges on the outer surface, which promote the diffusion ability of Zn 2+ and increased production of reactive oxygen species, and consequently lead to bacterial lysis. Furthermore, this study demonstrates excellent feasibility for the application of MgZnO NPs as fillers with good antibacterial activity, especially in antimicrobial food packaging applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Collagen VI is a ubiquitous extracellular matrix component that forms extensive microfibrillar networks in most connective tissues. In this study, we describe for the first time, to our knowledge, that the collagen VI von Willebrand factor type A-like domains exhibit a broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria in human skin infections in vivo. In silico sequence and structural analysis of VWA domains revealed that they contain cationic and amphipathic peptide sequence motifs, which might explain the antimicrobial nature of collagen VI. In vitro and in vivo studies show that these peptides exhibited significant antibacterial activity against Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa through membrane disruption. Our findings shed new light on the role of collagen VI-derived peptides in innate host defense and provide templates for development of peptide-based antibacterial therapies., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Macrolide antibiotics are used as anti-inflammatory agents, e.g., for prevention of exacerbations in chronic obstructive pulmonary disease and cystic fibrosis. Several studies have shown improved outcomes after the addition of macrolides to β-lactam antibiotics for treatment of severe community-acquired pneumonia. However, a beneficial effect of macrolides in treating Gram-negative bacterial airway infections, e.g., those caused by Pseudomonas aeruginosa , remains to be shown. Macrolide antibiotics have significant side effects, in particular, motility-stimulating activity in the gastrointestinal tract and promotion of bacterial resistance. In this study, EM703, a modified macrolide lacking antibiotic and motility-stimulating activities but with retained anti-inflammatory properties, was used as an adjunct treatment for experimental P. aeruginosa lung infection, in combination with a conventional antibiotic. Airway infections in BALB/cJRj mice were induced by nasal instillation of P. aeruginosa ; this was followed by treatment with the quinolone levofloxacin in the absence or presence of EM703. Survival, inflammatory responses, and cellular influx to the airways were monitored. Both pretreatment and simultaneous administration of EM703 dramatically improved survival in levofloxacin-treated mice with P. aeruginosa airway infections. In addition, EM703 reduced the levels of proinflammatory cytokines, increased the numbers of leukocytes in bronchoalveolar lavage fluid, and reduced the numbers of neutrophils present in lung tissue. In summary, the findings of this study show that the immunomodulatory properties of the modified macrolide EM703 can be important when treating Gram-negative pneumonia, as exemplified by P. aeruginosa infection in this study., (Copyright © 2017 American Society for Microbiology.)

In a Mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaA , dprE2 , rpsT , and parA displayed hypersusceptibility to antibiotics, including the β-lactams meropenem, ampicillin, amoxicillin, and cefotaxime. Sub-MIC levels of octoclothepin, a psychotic drug inhibiting ParA, phenocopied the parA insertion and enhanced the bactericidal activity of meropenem against Mycobacterium tuberculosis in combination with clavulanate. Our study identifies novel factors associated with antibiotic resistance, with implications in repurposing β-lactams for tuberculosis treatment., (Copyright © 2017 American Society for Microbiology.)

Pseudomonas aeruginosa airway infection is common in cystic fibrosis (CF), a disease also characterized by abundant extracellular DNA (eDNA) in the airways. The eDNA is mainly derived from neutrophils accumulating in the airways and contributes to a high sputum viscosity. The altered environment in the lower airways also paves the way for chronic P. aeruginosa infection. Here, we show that mice with P. aeruginosa airway infection have increased survival and decreased bacterial load after topical treatment with DNase. Furthermore, DNA from the sputum of CF patients showed increased bactericidal activity after treatment with DNase ex vivo. Both degraded DNA of neutrophil extracellular traps (NETs) and genomic DNA degraded by serum, acquired bactericidal activity against P. aeruginosa In vitro, small synthetic DNA-fragments (<100 base pairs) but not large fragments nor genomic DNA, were bactericidal against Gram-negative but not Gram-positive bacteria. The addition of divalent cations reduced bacterial killing, suggesting that chelation of divalent cations by DNA results in destabilization of the lipopolysaccharide (LPS) envelope. This is a novel antibacterial strategy where fragmentation of eDNA and DNA-fragments can be used to treat P. aeruginosa airway infection., (© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Tissue factor pathway inhibitor-2 (TFPI-2) is a serine protease inhibitor that exerts multiple physiological and patho-physiological activities involving the modulation of coagulation, angiogenesis, tumor invasion, and apoptosis. In previous studies we reported a novel role of human TFPI-2 in innate immunity by serving as a precursor for host defense peptides. Here we employed a number of TFPI-2 derived peptides from different vertebrate species and found that their antibacterial activity is evolutionary conserved although the amino acid sequence is not well conserved. We further studied the theraputic potential of one selected TFPI-2 derived peptide (mouse) in a murine sepsis model., Results: Hydrophobicity and net charge of many peptides play a important role in their host defence to invading bacterial pathogens. In vertebrates, the C-terminal portion of TFPI-2 consists of a highly conserved cluster of positively charged amino acids which may point to an antimicrobial activity. Thus a number of selected C-terminal TFPI-2 derived peptides from different species were synthesized and it was found that all of them exert antimicrobial activity against E. coli and P. aeruginosa. The peptide-mediated killing of E. coli was enhanced in human plasma, suggesting an involvement of the classical pathway of the complement. Under in vitro conditions the peptides displayed anti-coagulant activity by modulating the intrinsic pathway of coagulation and in vivo treatment with the mouse derived VKG24 peptide protects mice from an otherwise lethal LPS shock model., Conclusions: Our results suggest that the evolutionary conserved C-terminal part of TFPI-2 is an interesting agent for the development of novel antimicrobial therapies.

Despite the known association of several genes to clinical Isoniazid (INH) resistance, its molecular basis remains unknown in ~16% of clinical isolates of Mycobacterium tuberculosis (M. tb). While screening a set of Mycobacterium smegmatis (M. smegmatis) transposon mutants with altered colony morphology for differential susceptibility to INH, we found six resistant mutants and mapped their transposon insertion sites. The disrupted genes in six INH resistant mutants were homologs of M. tb ctaE, rplY, tatA, csd and tatB with one insertion mapping to the promoter region of M. smegmatis ctaE. MIC measurements indicated a wide spectrum of INH resistance in these mutants, with complementation analyses of four selected mutants with the cognate M. smegmatis genes and their M. tb homologs confirming the association of the disrupted genes with INH resistance. Our discovery of novel genes associated with INH resistance could lead to the identification of novel INH resistance mechanisms and possibly new diagnostic modalities as well., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Biomaterials used during surgery and wound treatment are of increasing importance in modern medical care. In the present study we set out to evaluate the addition of thrombin-derived host defense peptides to human acellular dermis (hAD, i.e. epiflex(®)). Antimicrobial activity of the functionalized hAD was demonstrated using radial diffusion and viable count assays against Gram-negative Escherichia coli, Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. Electron microscopy analyses showed that peptide-mediated bacterial killing led to reduced hAD degradation. Furthermore, peptide-functionalized hAD displayed endotoxin-binding activity in vitro, as evidenced by inhibition of NF-κB activation in human monocytic cells (THP-1 cells) and a reduction of pro-inflammatory cytokine production in whole blood in response to lipopolysaccharide stimulation. The dermal substitute retained its anti-endotoxic activity after washing, compatible with results showing that the hAD bound a significant amount of peptide. Furthermore, bacteria-induced contact activation was inhibited by peptide addition to the hAD. E. coli infected hAD, alone, or after treatment with the antiseptic substance polyhexamethylenebiguanide (PHMB), yielded NF-κB activation in THP-1 cells. The activation was abrogated by peptide addition. Thus, thrombin-derived HDPs should be of interest in the further development of new biomaterials with combined antimicrobial and anti-endotoxic functions for use in surgery and wound treatment., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Open fractures are common in battlefields, motor vehicle accidents, gunshot wounds, sports injuries, and high-energy falls. Such fractures are treated using hydroxyapatite (HA)-based bone graft substitutes. However, open fracture wounds are highly susceptible to bacterial infections. Hence, this study was focused on incorporating antibacterial properties to HA using silver (Ag) carrying self-assembled monolayers (SAMs). Also, the stability of Ag carrying SAMs on HA was investigated under sterilization and physiological conditions. Initially, the -COOH terminated phosphonic acid SAMs of two different chain lengths (11 carbon atoms - shorter chain and 16 carbon atoms - longer chain) were deposited on HA. Antibacterial SAMs (ASAMs) were prepared by chemically attaching Ag to shorter and longer chain SAMs coated HA. X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle goniometry collectively confirmed the attachment of Ag onto SAMs coated HA. The bacterial adhesion study showed that the adherence of Staphylococcus aureus was significantly reduced on ASAMs coated HA when compared to control-HA. The stability studies showed that gas plasma, dry heat and autoclave degraded most of the ASAMs on HA. UV irradiation did not damage the shorter chain ASAMs as vigorously as other treatments, while it degraded the longer chain ASAMs completely. Ethylene oxide treatment did not degrade the longer chain ASAMs unlike all other treatments but it severely damaged the shorter chain ASAMs. Both shorter and longer chain ASAMs significantly desorbed from the HA surfaces under physiological conditions although longer chain ASAMs exhibited better stability than shorter chain ASAMs. This study demonstrated the potential for using ASAMs to provide antibacterial properties to HA and the need for developing techniques to improve stability of SAMs under sterilization and physiological conditions., (Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)