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Representative chemical structures of some antimicrobial phytochemicals. Phytochemicals like phenolics, saponins, essential oils, terpenoids, alkaloids, and flavonids are the major classes showed antibacterial activity.
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Bacterial infections are raising serious concern across the globe. The effectiveness of conventional antibiotics is decreasing due to global emergence of multi-drug-resistant (MDR) bacterial pathogens. This process seems to be primarily caused by an indiscriminate and inappropriate use of antibiotics in non-infected patients and in the food industr...
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Bacteriophages (phages), natural predators of bacteria, are becoming increasingly attractive in medical and pharmaceutical applications. After their discovery almost a century ago, they have been particularly instrumental in the comprehension of basic molecular biology and genetics processes. The more recent emergence of multi-drug-resistant bacter...
This study involves partial characterisation of a lytic bacteriophage P.E1 against a multi drug-resistant clinical isolate of Escherichia coli, isolated from hospital sewage supply. The phage P.E1 has showed a narrow host range suitable for its use in phage therapy. Phage showed lytic activity up to 70°C and at alkaline conditions, but at higher ac...
Phage therapy is a promising treatment of multi-drug resistant (MDR) bacterial infections but is limited by the narrow host range of phage. To overcome this limitation, we developed a host range expansion (HRE) protocol that expands the host range of Pseudomonas aeruginosa-specific phage by cycles of co-incubation of phage with multiple P. aerugino...
Salmonella infections are the very challenging food borne enteric infections in humans from the past to the present era in medical science all over the world. Multiple antibiotics are usually and randomly used to treat this infection in both the developed and developing countries. Thus multiple drug resistant Salmonella strains are increasing more...
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... Issue) : 2024 healthy medicinal plant extracts comprising high therapeutic values (Satyavati et al., 1987;Sandhya et al., 2006). The serious impact of anti-microbial resistance (AMR) pathogens has spurred researchers to discover extra productive novel drugs as an alternative source to safeguard human beings their (Mandal et al. 2014). Modification in the structural and functional mechanism of microbes strengthens its resistance potency which facilitated the evolution of antibiotic-resistant microbial strains such as Methicillin-Resistant Staphylococcus aureus (MRSA), Extended-Spectrum Beta-Lactamases (ESBL), Klebsiella ST258 and Escherichia coli ST131. ...
... This characteristic enables AMPs to adhere to and infiltrate the bacterial cell wall bilayer, resulting in the formation of pores through mechanisms known as "toroidal-pore," "barrel-stave," and "carpet". Consequently, this process leads to the leakage of intracellular contents [81]. They come in a variety of structural forms including helical to linear and β-sheet structures (Fig. 4) [82]. ...
... The mechanisms for intracellular AMPs are summarized in Fig. 6. The antimicrobial activity of AMPs is particularly linked with its corresponding amino acid composition and physicochemical characteristics [81]. In addition to their direct antimicrobial activity, AMPs possess immunomodulatory properties, which stimulate the immune reaction of the host animal. ...
Globally, Mastitis is a disease commonly affecting dairy cattle which leads to the use of antimicrobials. The majority of mastitis etiological agents are bacterial pathogens and Staphylococcus aureus is the predominant causative agent. Antimicrobial treatment is administered mainly via intramammary and intramuscular routes. Due to increasing antimicrobial resistance (AMR) often associated with antimicrobial misuse, the treatment of mastitis is becoming challenging with less alternative treatment options. Besides, biofilms formation and ability of mastitis-causing bacteria to enter and adhere within the cells of the mammary epithelium complicate the treatment of bovine mastitis. In this review article, we address the challenges in treating mastitis through conventional antibiotic treatment because of the rising AMR, biofilms formation, and the intracellular survival of bacteria. This review article describes different alternative treatments including phytochemical compounds, antimicrobial peptides (AMPs), phage therapy, and Graphene Nanomaterial-Based Therapy that can potentially be further developed to complement existing antimicrobial therapy and overcome the growing threat of AMR in etiologies of mastitis.
... At 5 min, the disappearance of peaks at 657 and 1096 cm −1 , assigned to DNA, indicates that the host DNA is degraded. 68 Moreover, from 5 min onward, the biosynthesis of phage DNA and proteins takes place, 68 which is characterized by the appearance of peaks at 620, 743, 1113 and 1273 cm −1 (proteins) and the shi of the SERS peak assigned to DNA at 728 cm −1 (control) to 732 cm −1 (different time intervals). In addition to this, the appearance of the SERS peaks at 1331 cm −1 (assigned to DNA) and 1454 cm −1 (lipids) indicates the bacteriophage replication in the host bacteria. ...
Drug-resistant pathogenic bacteria are a major cause of infectious diseases in the world and they have become a major threat through the reduced efficacy of developed antibiotics. This issue can be addressed by using bacteriophages, which can kill lethal bacteria and prevent them from causing infections. Surface-enhanced Raman spectroscopy (SERS) is a promising technique for studying the degradation of infectious bacteria by the interaction of bacteriophages to break the vicious cycle of drug-resistant bacteria and help to develop chemotherapy-independent remedial strategies. The phage (viruses)-sensitive Staphylococcus aureus (S. aureus) bacteria are exposed to bacteriophages (Siphoviridae family) in the time frame from 0 min (control) to 50 minutes with intervals of 5 minutes and characterized by SERS using silver nanoparticles as SERS substrate. This allows us to explore the effects of the bacteriophages against lethal bacteria (S. aureus) at different time intervals. The differentiating SERS bands are observed at 575 (C–C skeletal mode), 620 (phenylalanine), 649 (tyrosine, guanine (ring breathing)), 657 (guanine (COO deformation)), 728–735 (adenine, glycosidic ring mode), 796 (tyrosine (C–N stretching)), 957 (C–N stretching (amide lipopolysaccharides)), 1096 (PO2 (nucleic acid)), 1113 (phenylalanine), 1249 (CH2 of amide III, N–H bending and C–O stretching (amide III)), 1273 (CH2, N–H, C–N, amide III), 1331 (C–N stretching mode of adenine), 1373 (in nucleic acids (ring breathing modes of the DNA/RNA bases)) and 1454 cm⁻¹ (CH2 deformation of saturated lipids), indicating the degradation of bacteria and replication of bacteriophages. Multivariate data analysis was performed by employing principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to study the biochemical differences in the S. aureus bacteria infected by the bacteriophage. The SERS spectral data sets were successfully differentiated by PLS-DA with 94.47% sensitivity, 98.61% specificity, 94.44% precision, 98.88% accuracy and 81.06% area under the curve (AUC), which shows that at 50 min interval S. aureus bacteria is degraded by the replicating bacteriophages.
... Antimicrobial peptides (AMPs) have been considered as an alternative therapeutic agent to conventional antibiotics [10,11]. These naturally occurring peptides, typically consisting of less than 100 hydrophobic and cationic amino acids in a certain sequence combination, exert their antibacterial effects mainly by disrupting the integrity of bacterial cell membranes [12]. ...
Rationale: Antimicrobial peptide LL-37 has been recognized as a favorable alternative to antibiotics due to its broad antibacterial spectrum, low resistance development and diverse biological activities. However, its high manufactory cost, poor proteolytic stability, and unpredictable cytotoxicity seriously hindered its medical translation.
Methods: To push the frontiers of its clinical application, all-hydrocarbon stapling strategy was exploited here for the structural modification of KR-12, the core and minimal fragment of LL-37.
Results: Based on a library of KR-12 derivatives that designed and synthesized to be stapled at positions of either i, i+4 or i, i+7, structure to activity relationship was investigated. Among them, KR-12(Q5, D9) with the glutamine and aspartic acid residues stapled displayed increased helical content and positive charge. The reinforced α-helical conformation not only protected it from proteolytic hydrolysis but also improved its antibacterial efficacy via effective membrane perturbation and anti-inflammatory efficacy via compact LPS binding. Besides, the increased positive charge endowed it with an enhanced therapeutic index. On infected wound mouse model, it was demonstrated to eliminate bacteria and promote wound closure and regeneration effectively.
Conclusion: Overall, the all-hydrocarbon stapling was proven to lay the foundation for the future development of antibacterial agents. KR-12(Q5, D9) could serve as a lead compound for the clinical treatment of bacterial infections.
... Combination therapy: Combining multiple antibiotics with different mechanisms of action can help overcome resistance mechanisms and improve treatment outcomes. Non-conventional alternative treatment strategies: Exploration of the possibility of using phage therapy ( Fig. 6), vaccination (as stated earlier), natural or synthetic antimicrobial peptides, and the use of AI to develop unique antibiotics are among the new regimes that could provide unique solutions in the future [167][168][169][170]. Nanorobotics technology is also a new area of research that could be investigated for its benefits in this challenge. ...
... Integrated Approach: A comprehensive approach that considers both the benefits and risks of B. cepacia is necessary for its responsible use and effective management. In essence, B. cepacia presents a complex challenge [169,170] with both positive and negative aspects. Recognizing its potential benefits while prioritizing the mitigation of health risks is crucial for navigating its role in our world. ...
This review explores the paradox of Burkholderia species, a bacterium capable of both beneficial and harmful actions. Genus Burkholderia is a Gram-negative, rod-shaped, motile bacterium with remarkable genetic diversity. It can thrive in diverse environments and exchange genes with other bacteria through horizontal gene transfer. The ambivalence of Burkholderia lies in its potential to act as both a plant pathogen and an opportunistic human pathogen. Early isolations linked it to urinary tract infections and meningitis. However, its true threat emerged for individuals with cystic fibrosis and chronic granulomatous disease, who are susceptible to severe Burkholderia infections like pneumonia and septicemia. Beyond healthcare, Burkholderia exhibits useful applications in agriculture and biotechnology. Certain strains promote plant growth by fixing nitrogen, solubilizing phosphorus, and producing growth hormones. Burkholderia offers promise in bioremediation, degrading pollutants like hydrocarbons, pesticides and heavy metals. However, responsible application is crucial. Environmental contamination, biofilm formation, and potential plant diseases raise concerns. Careful consideration and ongoing research are necessary to mitigate these risks. Biotechnology leverages Burkholderia's diverse functionalities. It produces bioplastics, enzymes, and rhamnolipids with potential applications in various industries. Despite its benefits, it poses a healthcare risk to immunocompromised individuals, causing respiratory infections and hospital outbreaks. Its multi-drug resistance necessitates strict infection control protocols and development of novel treatment strategies. In conclusion, Burkholderia presents a complex picture. While its potential benefits in agriculture and biotechnology are promising, responsible use and continuous research are paramount to exploit its advantages and mitigate potential hazards.
... Esto es posible dado que los fagos expresan genes que pueden inhibir el crecimiento de las bacterias, las cuales pueden ser patogénicas para sus respectivos hospederos, como en el caso del hombre. El uso de los de los fagos como alternativa al uso de antibióticos convencionales ha sido explorada desde hace años y es conocida como fagoterapia (Sulakvelidze et al., 2001;Hagens et al., 2004;Harper & Enright, 2011;Mandal et al., 2014;Kaur, 2016). En este sentido, el modelo de D. melanogaster también ha sido empleado para evaluar la eficacia antibacterial de los fagos contra un patógeno humano oportunista, como lo es Pseudomonas aeruginosa (Heo et al., 2009;Jang et al., 2018). ...
El uso de los de los fagos como alternativa al uso de antibióticos convencionales ha sido explorada desde hace años y es conocida como fagoterapia (Sulakvelidze et al., 2001; Hagens et al., 2004; Harper & Enri¬ght, 2011; Mandal et al., 2014; Kaur, 2016). En este sentido, el modelo de D. melanogaster también ha sido empleado para evaluar la eficacia antibacterial de los fagos contra un patógeno humano oportunista, como lo es Pseudomonas aeruginosa (Heo et al., 2009; Jang et al., 2018). Esto es sólo una muestra de un enfoque que promete arrojar más información sobre el uso potencial de los fagos, aunque, y todavía más importante, también representa un nuevo punto de partida para identificar e inda¬gar sobre interacciones todavía no descritas. Si un solo modelo como D. melanogaster ha sido capaz de aportar tanto a la biología, ahora falta esperar qué nos puede decir ésta en conjunto a sus bacterias y virus en conjunto.
... There have been several attempts to develop alternative therapies against antibioticresistant S. aureus, either using antibiotics with adjuvants, antimicrobial peptides (AMP), photodynamic therapy, bacteriophage therapy, or the use of nanoparticles and phytochemicals as antibacterial agents [5,6]. For instance, a combination of two antibiotics, Fosfomycin protein. ...
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most dreadful pathogens relevant in community and nosocomial-related infections around the world. Resensitising MRSA to antibiotics, once it became resistant, was a tough choice due to the high adaptability of this bacteria to savage conditions. This study aimed to create a chimeric enzybiotic against MRSA and test its efficiency, either individually or in combination with antibiotics. The novel enzybiotic BAC100 was constructed by fusing the catalytic domain from the bacteriocin BacL1 from Enterococcus faecalis with the cell-wall-binding domain from protein P17 of Staphylococcus aureus bacteriophage ϕ44AHJD. Apart from its partial lone activity, BAC100 was found to resensitise the MRSA strain to traditional antibiotics, including ampicillin and tetracycline. Both drugs were able to reduce live MRSA cells by 85 and 90%, respectively, within 60 min of treatment together with BAC100. However, no significant activity was observed against MRSA when these drugs were tested independently, pointing to the inherent resistance of MRSA against these conventional antibiotics. To our knowledge, this is one of the first instances where an engineered enzybiotic was found to resensitise MRSA to conventional antibiotics. This study will pave the way for the development of similar peptides that can be used together with antibiotics against gruesome pathogens of clinical importance.
... That results in the origin of multiple drug resistance (MDR) bacterial strains in animal sector. Presence of such MDR strains in food chain that possess common virulence markers as human Uro-pathogenic E. coli strains (UPEC) can lead to greater exposure of human population to these MDR strains with probable zoonotic potential and pose threat to human health resulting in regular outbreaks leaving little choice for physicians to treat them 12 To control such MDR variants to non-infectious levels phage therapy has been a subject of interest from a long time 13,14 . Bacteriophages are natural killers of bacteria and are host specific unlike broad spectrum antibiotics that affect commensal bacterial populations along with pathogenic ones. ...
Avian pathogenic E. coli (APEC) is associated with local and systemic infections in poultry, ducks, turkeys, and many other avian species, leading to heavy economical losses. These APEC strains are presumed to possess zoonotic potential due to common virulence markers that can cause urinary tract infections in humans. The prophylactic use of antibiotics in the poultry sector has led to the rapid emergence of Multiple Drug Resistant (MDR) APEC strains that act as reservoirs and put human populations at risk. This calls for consideration of alternative strategies to decrease the bacterial load. Here, we report isolation, preliminary characterization, and genome analysis of two novel lytic phage species (Escherichia phage SKA49 and Escherichia phage SKA64) against MDR strain of APEC, QZJM25. Both phages were able to keep QZJM25 growth significantly less than the untreated bacterial control for approximately 18 h. The host range was tested against Escherichia coli strains of poultry and human UTI infections. SKA49 had a broader host range in contrast to SKA64. Both phages were stable at 37 °C only. Their genome analysis indicated their safety as no recombination, integration and host virulence genes were identified. Both these phages can be good candidates for control of APEC strains based on their lysis potential.
... Green-synthesized AgNPs from Annona squamosa increased fibroblast differentiation to myofibroblasts, thus enhancing wound-healing capacity [55]. Mondal et al. summarized tissue regeneration and the wound constriction of injured sites [56]. Other studies also showed that greensynthesized AgNPs treated groups have well-developed collagen fibers with developed blood vessels [57] and enhanced angiogenesis [58]. ...
Developing an efficient and cost-effective wound-healing substance to treat wounds and regenerate skin is desperately needed in the current world. Antioxidant substances are gaining interest in wound healing, and green-synthesized silver nanoparticles have drawn considerable attention in biomedical applications due to their efficient, cost-effective, and non-toxic nature. The present study evaluated in vivo wound healing and antioxidant activities of silver nanoparticles from Azadirachta indica (AAgNPs) and Catharanthus roseus (CAgNPs) leaf extracts in BALB/c mice. We found rapid wound healing, higher collagen deposition, and increased DNA and protein content in AAgNPs- and CAgNPs (1% w/w)-treated wounds than in control and vehicle control wounds. Skin antioxidant enzyme activities (SOD, catalase, GPx, GR) were significantly (p < 0.05) increased after 11 days CAgNPs and AAgNPs treatment. Furthermore, the topical application of CAgNPs and AAgNPs tends to suppress lipid peroxidation in wounded skin samples. Histopathological images evidenced decreased scar width, epithelium restoration, fine collagen deposition, and fewer inflammatory cells in CAgNPs and AAgNPs applied wounds. In vitro, the free radical scavenging activity of CAgNPs and AAgNPs was demonstrated by DPPH and ABTS radical scavenging assays. Our findings suggest that silver nanoparticles prepared from C. roseus and A. indica leaf extracts increased antioxidant status and improved the wound-healing process in mice. Therefore, these silver nanoparticles could be potential natural antioxidants to treat wounds.
... Green-synthesized AgNPs from Annona squamosa increased fibroblast differentiation to myofibroblasts, thus enhancing wound-healing capacity [55]. Mondal et al. summarized tissue regeneration and the wound constriction of injured sites [56]. Other studies also showed that greensynthesized AgNPs treated groups have well-developed collagen fibers with developed blood vessels [57] and enhanced angiogenesis [58]. ...
