Daunorubicin (DNR) is an anthracycline antibiotic originating from soil-dwelling actinobacteria extensively used to treat malignant tumors. Over the decades, extensive attempts were made to enhance the production of anthracyclines by introducing genetic modifications and mutations in combination with media optimization, but the target production levels remain comparatively low. Developing an appropriate culture medium to maximize the yield of DNR and preventing autotoxicity for the producing organism remains a challenge. Our prospective review sheds light on a method involving perturbation that enhances the precursors to regulate the type II PKS pathway, enhancing cells' capacity to increase secondary metabolite production. The suggested method also entails the preparation of culture media for the cultivation of Streptomyces sp. and enhanced yield of DNR, as well as making it inactive with iron or its reduced forms following efflux from the producer. The iron or iron-DNR complex is encapsulated by oleic acid or lipid micelle layers in the culture media, finally resulting in the generated inactive DNR and the DNR-iron-oil complex. This idea has the potential to protect the producer organism from autotoxicity and prevent the inhibition of metabolite production. The approach of substituting sugar with oil in culture media has a dual role wherein it promotes Streptomyces growth by utilizing lipids as an energy source and encapsulating the generated DNR-iron complex in the medium. In this review, we discussed aspects like anthracycline producers, biosynthesis pathways, and gene regulation; side effects of DNR; mechanisms for autotoxicity evasion; and culture media components for the enhancement of DNR production in Streptomyces sp. We anticipate that our work will help researchers working with secondary metabolites production and decipher a methodology that would enhance DNR yield and facilitate the extraction of the resulting DNR by lowering costs in large-scale fermentation.

• Klíčová slova
• Streptomyces, anthracyclines, autotoxicity, daunomycin, efflux, enhancement, oil-based medium,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Covalent organic frameworks (COFs) are crystal-like organic structures such as cartography buildings prepared from appropriately pre-designed construction block precursors. Moreover, after the expansion of the first COF in 2005, numerous researchers have been developing different materials for versatile applications such as sensing/imaging, cancer theranostics, drug delivery, tissue engineering, wound healing, and antimicrobials. COFs have harmonious pore size, enduring porosity, thermal stability, and low density. In addition, a wide variety of functional groups could be implanted during their construction to provide desired constituents, including antibodies and enzymes. The reticular organic frameworks comprising porous hybrid materials connected via a covalent bond have been studied for improving wound healing and dressing applications due to their long-standing antibacterial properties. Several COF-based systems have been planned for controlled drug delivery with wound healing purposes, targeting drugs to efficiently inhibit the growth of pathogenic microorganisms at the wound spot. In addition, COFs can be deployed for combinational therapy using photodynamic and photothermal antibacterial therapy along with drug delivery for healing chronic wounds and bacterial infections. Herein, the most recent advancements pertaining to the applications of COF-based systems against bacterial infections and for wound healing are considered, concentrating on challenges and future guidelines.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.

• MeSH
• antibakteriální látky dějiny   metabolismus   MeSH
• Arthrodermataceae genetika   metabolismus   MeSH
• beta-laktamy metabolismus   MeSH
• dějiny 20. století MeSH
• fylogeneze MeSH
• geografická kartografie MeSH
• ježkovití metabolismus   mikrobiologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus genetika   metabolismus   MeSH
• molekulární evoluce MeSH
• One Health MeSH
• peniciliny biosyntéza   MeSH
• rezistence na methicilin genetika   MeSH
• selekce (genetika) genetika   MeSH
• zvířata MeSH
• Check Tag
• dějiny 20. století MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Dánsko MeSH
• Evropa MeSH
• Nový Zéland MeSH
• Názvy látek
• antibakteriální látky MeSH
• beta-laktamy MeSH
• peniciliny MeSH

The incidence of syphilis has risen worldwide in the last decade in spite of being an easily treated infection. The causative agent of this sexually transmitted disease is the bacterium Treponema pallidum subspecies pallidum (TPA), very closely related to subsp. pertenue (TPE) and endemicum (TEN), responsible for the human treponematoses yaws and bejel, respectively. Although much focus has been placed on the question of the spatial and temporary origins of TPA, the processes driving the evolution and epidemiological spread of TPA since its divergence from TPE and TEN are not well understood. Here, we investigate the effects of recombination and selection as forces of genetic diversity and differentiation acting during the evolution of T. pallidum subspecies. Using a custom-tailored procedure, named phylogenetic incongruence method, with 75 complete genome sequences, we found strong evidence for recombination among the T. pallidum subspecies, involving 12 genes and 21 events. In most cases, only one recombination event per gene was detected and all but one event corresponded to intersubspecies transfers, from TPE/TEN to TPA. We found a clear signal of natural selection acting on the recombinant genes, which is more intense in their recombinant regions. The phylogenetic location of the recombination events detected and the functional role of the genes with signals of positive selection suggest that these evolutionary processes had a key role in the evolution and recent expansion of the syphilis bacteria and significant implications for the selection of vaccine candidates and the design of a broadly protective syphilis vaccine.

• Klíčová slova
• genome analysis, phylogenetic congruence, recombination, selection, treponematoses,
• MeSH
• frambézie * mikrobiologie   MeSH
• fylogeneze MeSH
• infekce bakteriemi rodu Treponema * mikrobiologie   MeSH
• lidé MeSH
• syfilis * epidemiologie   mikrobiologie   MeSH
• Treponema pallidum genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Drug resistance has now become a serious concern in the domain of microbial infection. Bacteria are becoming smarter by displaying a variety of mechanisms during drug resistance. It is not only helping bacteria to adapt nicely in adverse environment but it also makes a smart system for better availability of nutritional status for microorganisms. In this domain, pathogenic bacteria are extensively studied and their mechanism for drug resistance is well explored. The common modes in bacterial resistance include degradation of antibiotics by enzymes, antibiotic target modification or inactivation by enzymatic actions, complete replacement of antibiotic targets, quorum sensing (QS) mechanism, and efflux pump-based extrusion of antibiotics. In this review, various mechanisms of drug resistance in bacteria have been highlighted with giving the importance of efflux pumps. This can be explored as a knowledge source for the management of a variety of bacterial infections, related disease and vibrant clue for next-generation drug development.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• Bacteria * účinky léků   genetika   metabolismus   MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• léková rezistence * fyziologie   MeSH
• membránové transportní proteiny * genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky * MeSH
• bakteriální proteiny MeSH
• membránové transportní proteiny * MeSH

An inexorable switch from antibiotics has become a major desideratum to overcome antibiotic resistance. Bacteriocin from Lactobacillus casei, a cardinal probiotic was used to design novel antibacterial peptides named as Probiotic Bacteriocin Derived and Modified (PBDM) peptides (PBDM1: YKWFAHLIKGLC and PBDM2: YKWFRHLIKKLC). The loop-shaped 3D structure of peptides was characterized in silico via molecular dynamics simulation as well as biophysically via spectroscopic methods. Thereafter, in vitro results against multidrug resistant bacterial strains and hospital samples demonstrated the strong antimicrobial activity of PBDM peptides. Further, in vivo studies with PBDM peptides showed downright recovery of balb/c mice from Vancomycin Resistant Staphylococcus aureus (VRSA) infection to its healthy condition. Thereafter, in vitro study with human epithelial cells showed no significant cytotoxic effects with high biocompatibility and good hemocompatibility. In conclusion, PBDM peptides displayed significant antibacterial activity against certain drug resistant bacteria which cause infections in human beings. Future analysis are required to unveil its mechanism of action in order to execute it as an alternative to antibiotics.

• Klíčová slova
• antibacterial peptides, antibiotics, bacteria, infections, multidrug resistance,
• Publikační typ
• časopisecké články MeSH

The upsurge of multiple drug resistance (MDR) bacteria substantially diminishes the effectiveness of antibiotic arsenal and therefore intensifies the rate of therapeutic failure. The major factor in MDR is efflux pump-mediated resistance. A unique pump can make bacteria withstand a wide range of structurally diverse compounds. Therefore, their inhibition is a promising route to eliminate resistance phenomenon in bacteria. Phytochemicals are excellent alternatives as resistance-modifying agents. They can directly kill bacteria or interact with the crucial events of pathogenicity, thereby decreasing the ability of bacteria to develop resistance. Numerous botanicals display noteworthy efflux pumps inhibitory activities. Edible plants are of growing interest. Likewise, some plant families would be excellent sources of efflux pump inhibitors (EPIs) including Apocynaceae, Berberidaceae, Convolvulaceae, Cucurbitaceae, Fabaceae, Lamiaceae, and Zingiberaceae. Easily applicable methods for screening plant-derived EPIs include checkerboard synergy test, berberine uptake assay and ethidium bromide test. In silico high-throughput virtual detection can be evaluated as a criterion of excluding compounds with efflux substrate-like characteristics, thereby improving the selection process and extending the identification of EPIs. To ascertain the efflux activity inhibition, real-time PCR and quantitative mass spectrometry can be applied. This review emphasizes on efflux pumps and their roles in transmitting bacterial resistance and an update plant-derived EPIs and strategies for identification.

• Klíčová slova
• Edible plants, Efflux activity assays, Efflux pump inhibitors, Multidrug-resistant bacteria, Plant secondary metabolites,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Antibiotic-resistant bacterial infections have become global issues for public health, which increases the utter need to develop alternatives to antibiotics. Here, the HSER (Homo sapiens retinoic acid receptor) peptide was designed from retinoic acid receptor responder protein 2 of Homo sapiens, and was conjugated with synthesized CQDs (carbon quantum dots) for enhanced antibacterial activity in combination, as individually they are not highly effective. The HSER-CQDs were characterized using spectrophotometer, HPLC coupled with electrospray-ionization quadrupole time-of-flight mass spectrometer (ESI-qTOF) mass spectrometer, zeta potential, zeta size, and FTIR. Thereafter, the antibacterial activity against Vancomycin-Resistant Staphylococcus aureus (VRSA) and Escherichia coli (carbapenem resistant) was studied using growth curve analysis, further supported by microscopic images showing the presence of cell debris and dead bacterial cells. The antibacterial mechanism of HSER-CQDs was observed to be via cell wall disruption and also interaction with gDNA (genomic DNA). Finally, toxicity test against normal human epithelial cells showed no toxicity, confirmed by microscopic analysis. Thus, the HSER-CQDs conjugate, having high stability and low toxicity with prominent antibacterial activity, can be used as a potential antibacterial agent.

• Klíčová slova
• antibacterial activity, antibiotic-resistant, bacterial infections, carbon quantum dots, toxicity,
• Publikační typ
• časopisecké články MeSH

Biodegradable polymers are promising materials for use in medical applications such as stents. Their properties are comparable to commercially available resistant metal and polymeric stents, which have several major problems, such as stent migration and stent clogging due to microbial biofilm. Consequently, conventional stents have to be removed operatively from the patient's body, which presents a number of complications and can also endanger the patient's life. Biodegradable stents disintegrate into basic substances that decompose in the human body, and no surgery is required. This review focuses on the specific use of stents in the human body, the problems of microbial biofilm, and possibilities of preventing microbial growth by modifying polymers with antimicrobial agents.

• Klíčová slova
• antimicrobial agents, antimicrobial effects, biodegradable polymer, medicine, polylactide, stent,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Environmental pollutants, including antibiotics (ATBs), have become an increasingly common health hazard in the last several decades. Overdose and abuse of ATBs led to the emergence of antibiotic-resistant genes (ARGs), which represent a serious health threat. Moreover, water bodies and reservoirs are places where a wide range of bacterial species with ARGs originate, owing to the strong selective pressure from presence of ATB residues. In this regard, graphene oxide (GO) has been utilised in several fields including remediation of the environment. In this review, we present a brief overview of resistant genes of frequently used ATBs, their occurrence in the environment and their behaviour. Further, we discussed the factors influencing the binding of nucleic acids and the response of ARGs to GO, including the presence of salts in the water environment or water pH, because of intrinsic properties of GO of not only binding to nucleic acids but also catalysing their decomposition. This would be helpful in designing new types of water treatment facilities.

• Klíčová slova
• Antibiotics, Environment, Genes, Graphene oxide, Nanomaterials, Pollution, Wastewater,
• MeSH
• antibakteriální látky analýza   MeSH
• bakteriální geny * MeSH
• bakteriální léková rezistence genetika   MeSH
• chemické látky znečišťující vodu analýza   MeSH
• čištění vody MeSH
• grafit chemie   MeSH
• odpadní voda chemie   mikrobiologie   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• chemické látky znečišťující vodu MeSH
• grafit MeSH
• graphene oxide MeSH Prohlížeč
• odpadní voda MeSH