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Pseudomonas aeruginosa is often identified as the causative agent in nosocomial infections. Their adapted resistance makes them strong towards antimicrobial treatments. They protect and empower their survival behind strong biofilm architecture that works as their armor toward antimicrobial therapy. Additionally, P. aeruginosa generates virulence factors, contributing to chronic infection and recalcitrant phenotypic characteristics. The current study utilizes the benevolence of nanotechnology to develop an alternate technique to control the spreading of P. aeruginosa by limiting its biofilm and virulence development. This study used a natural compound, tetramethylpyrazine, to generate gold nanoparticles. Tetramethylpyrazine-gold nanoparticles (Tet-AuNPs) were presented in spherical shapes, with an average size of 168 ± 52.49 nm and a zeta potential of -12.22 ± 2.06 mV. The minimum inhibition concentration (MIC) of Tet-AuNPs that proved more than 90 % effective in inhibiting P. aeruginosa was 256 µg/mL. Additionally, it also shows antibacterial activities against Staphylococcus aureus (MIC, 256 µg/mL), Streptococcus mutans (MIC, 128 µg/mL), Klebsiella pneumoniae (MIC, 128 µg/mL), Listeria monocytogenes (MIC, 256 µg/mL), and Escherichia coli (MIC, 256 µg/mL). The sub-MIC values of Tet-AuNPs significantly inhibited the early-stage biofilm formation of P. aeruginosa. Moreover, this concentration strongly affected hemolysis, protease activity, and different forms of motilities in P. aeruginosa. Additionally, Tet-AuNPs destroyed the well-established mature biofilm of P. aeruginosa. The expression of genes linked with the biofilm formation and virulence in P. aeruginosa treated with sub-MIC doses of Tet-AuNPs was shown to be significantly suppressed. Gene expression studies support biofilm- and virulence-suppressing effects of Tet-AuNPs at the phenotypic level.
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Antibacterianos , Biofilmes , Ouro , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Pirazinas , Fatores de Virulência , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Ouro/química , Ouro/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Fatores de Virulência/genética , Antibacterianos/farmacologia , Antibacterianos/química , Pirazinas/farmacologia , Nanopartículas Metálicas/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Klebsiella pneumoniae/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/genética , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/genéticaRESUMO
The rapidly rising antimicrobial resistance (AMR) in pathogenic bacteria has become one of the most serious public health challenges, with a high death rate. Most pathogenic bacteria have been recognized as a source of AMR and a primary barrier to antimicrobial treatment failure due to the development of biofilms and the production of virulence factors. In this work, nanotechnology was employed as a substitute method to control the formation of biofilms and attenuate virulence features in Pseudomonas aeruginosa and Staphylococcus aureus. We synthesized biocompatible gold nanoparticles from marine-derived laminarin as potential biofilm and virulence treatments. Laminarin-gold nanoparticles (Lam-AuNPs) have been identified as spherical, 49.84 ± 7.32 nm in size and - 26.49 ± 1.29 mV zeta potential. The MIC value of Lam-AuNPs against several drug-resistant microbial pathogens varied from 2 to 1024 µg/mL in both standard and host-mimicking media. Sub-MIC values of Lam-AuNPs were reported to effectively reduce the production of P. aeruginosa and S. aureus biofilms in both standard and host-mimicking growth media. Furthermore, the sub-MIC of Lam-AuNPs strongly reduced hemolysis, pyocyanin, pyoverdine, protease, and several forms of flagellar and pili-mediated motility in P. aeruginosa. Lam-AuNPs also inhibited S. aureus hemolysis and the production of amyloid fibrils. The Lam-AuNPs strongly dispersed the preformed mature biofilm of these pathogens in a dose-dependent manner. The Lam-AuNPs would be considered an alternative antibiofilm and antivirulence agent to control P. aeruginosa and S. aureus infections. KEY POINTS: ⢠Lam-AuNPs were biosynthesized to control biofilm and virulence. ⢠Lam-AuNPs show effective biofilm inhibition in standard and host-mimicking media. ⢠Lam-AuNPs suppress various virulence factors of P. aeruginosa and S. aureus.
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Anti-Infecciosos , Glucanos , Nanopartículas Metálicas , Humanos , Ouro/farmacologia , Hemólise , Staphylococcus aureus , Biofilmes , Fatores de VirulênciaRESUMO
Acinetobacter baumannii is a Gram-negative opportunistic zoonotic pathogenic bacterium that causes nosocomial infections ranging from minor to life-threatening. The clinical importance of this zoonotic pathogen is rapidly increasing due to the development of multiple resistance mechanisms and the synthesis of numerous virulence factors. Although no flagellum-mediated motility exists, it may move through twitching or surface-associated motility. Twitching motility is a coordinated multicellular movement caused by the extension, attachment, and retraction of type IV pili, which are involved in surface adherence and biofilm formation. Surface-associated motility is a kind of movement that does not need appendages and is most likely driven by the release of extra polymeric molecules. This kind of motility is linked to the production of 1,3-diaminopropane, lipooligosaccharide formation, natural competence, and efflux pump proteins. Since A. baumannii's virulence qualities are directly tied to motility, it is possible that its motility may be used as a specialized preventative or therapeutic measure. The current review detailed the signaling mechanism and involvement of various proteins in controlling A. baumannii motility. As a result, we have thoroughly addressed the role of natural and synthetic compounds that impede A. baumannii motility, as well as the underlying action mechanisms. Understanding the regulatory mechanisms behind A. baumannii's motility features will aid in the development of therapeutic drugs to control its infection. KEY POINTS: ⢠Acinetobacter baumannii exhibits multiple resistance mechanisms. ⢠A. baumannii can move owing to twitching and surface-associated motility. ⢠Natural and synthetic compounds can attenuate A. baumannii motility.
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Acinetobacter baumannii , Acinetobacter baumannii/metabolismo , Virulência , Fatores de Virulência/metabolismo , Proteínas de Bactérias/metabolismo , Fímbrias Bacterianas/metabolismo , Biofilmes , Antibacterianos/metabolismoRESUMO
Pseudomonas aeruginosa can efficiently adapt to changing environmental conditions due to its ubiquitous nature, intrinsic/acquired/adaptive resistance mechanisms, high metabolic versatility, and the production of numerous virulence factors. As a result, P. aeruginosa becomes an opportunistic pathogen, causing chronic infection in the lungs and several organs of patients suffering from cystic fibrosis. Biofilm established by P. aeruginosa in host tissues and medical device surfaces has been identified as a major obstruction to antimicrobial therapy. P. aeruginosa is very likely to be closely associated with the various microorganisms in the host tissues or organs in a pathogenic or nonpathogenic behavior. Aside from host-derived molecules, other beneficial and pathogenic microorganisms produce a diverse range of secondary metabolites that either directly or indirectly favor the persistence of P. aeruginosa. Thus, it is critical to understand how P. aeruginosa interacts with different molecules and ions in the host and abiotic environment to produce extracellular polymeric substances and virulence factors. Thus, the current review discusses how various natural and synthetic molecules in the environment induce biofilm formation and the production of multiple virulence factors.
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Nisin is a naturally occurring bioactive small peptide produced by Lactococcus lactis subsp. lactis and belongs to the Type A (I) lantibiotics. Due to its potent antimicrobial activity, it has been broadly employed to preserve various food materials as well as to combat a variety of microbial pathogens. The present review discusses the antimicrobial properties of nisin and different types of their derivatives employed to treat microbial pathogens with a detailed underlying mechanism of action. Several alternative strategies such as combination, conjugation, and nanoformulations have been discussed in order to address several issues such as rapid degradation, instability, and reduced activity due to the various environmental factors that arise in the applications of nisin. Furthermore, the evolutionary relationship of many nisin genes from different nisin-producing bacterial species has been investigated. A detailed description of the natural and bioengineered nisin variants, as well as the underlying action mechanisms, has also been provided. The chemistry used to apply nisin in conjugation with natural or synthetic compounds as a synergetic mode of antimicrobial action has also been thoroughly discussed. The current review will be useful in learning about recent and past research that has been performed on nisin and its derivatives as antimicrobial agents.
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Bacteriocinas , Nisina , Nisina/farmacologia , Bacteriocinas/genética , Bacteriocinas/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Genes BacterianosRESUMO
The co-isolation of Staphylococcus aureus and Candida albicans from host tissues and organs and their in vitro and in vivo interaction studies suggest a synergistic relationship in forming polymicrobial biofilms. In particular, during polymicrobial biofilm formation, S. aureus becomes coated in the extracellular matrix secreted by C. albicans, leading to enhanced resistance to antibiotics. Accordingly, understanding the interactions between S. aureus and C. albicans in polymicrobial biofilms is of utmost importance in establishing treatment strategies for polymicrobial infections. As an alternate technique, nanoparticles were used in this investigation to suppress polymicrobial biofilm. The current study aims to manufacture gold nanoparticles (AuNPs) using phloroglucinol (PG), a natural chemical, and test their inhibitory capabilities against S. aureus and C. albicans biofilms in standard and host-mimicking media (like saliva and sputum). PG-AuNPs have a spherical form with an average size of 46.71 ± 6.40 nm. The minimum inhibitory concentration (MIC) values differed when PG-AuNPs were evaluated in the standard and host-mimicking artificial media. The MIC of PG-AuNPs against S. aureus and C. albicans was 2048 µg/mL in both the standard and artificial sputum media. However, the MIC in saliva was only 128 µg/mL. The initial stage polymicrobial biofilm of S. aureus and C. albicans was dramatically decreased at the sub-MIC of PG-AuNPs in both standard and host-mimicking media. S. aureus and C. albicans mature polymicrobial biofilms were more effectively eliminated by MIC and sub-MIC of PG-AuNPs. This study indicates that PG-AuNPs have the ability to limit the formation of polymicrobial biofilms caused by bacterial and fungal diseases.
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Candida albicans , Nanopartículas Metálicas , Ouro/farmacologia , Staphylococcus aureus , BiofilmesRESUMO
Cyclic bis-(3', 5')-dimeric guanosine monophosphate (c-di-GMP) is ubiquitous in many bacterial species, where it functions as a nucleotide-based secondary messenger and is a vital regulator of numerous biological processes. Due to its ubiquity, most bacterial species possess a wide range of downstream receptors that has a binding affinity to c-di-GMP and elicit output responses. In eukaryotes, several enzymes and riboswitches operate as receptors that interact with c-di-GMP and transduce cellular or environmental signals. This review examines the functional variety of receptors in prokaryotic and eukaryotic systems that exhibit distinct biological responses after interacting with c-di-GMP. Evolutionary relationships and similarities in distance among the c-di-GMP receptors in various bacterial species were evaluated to understand their specificities. Furthermore, residues of receptors involved in c-di-GMP binding are summarized. This review facilitates the understanding of how distinct receptors from different origins bind c-di-GMP equally well, yet fulfill diverse biological roles at the interspecies, intraspecies, and interkingdom levels. Furthermore, it also highlights c-di-GMP receptors as potential therapeutic targets, particularly those found in pathogenic microorganisms. Video Abstract.
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GMP Cíclico , Eucariotos , Fosforilação , PolímerosRESUMO
Pseudmonas aeruginosa is a Gram-negative bacterium known to be ubiquitous and recognized as one of the leading causes of infections such as respiratory, urinary tract, burns, cystic fibrosis, and in immunocompromised individuals. Failure of antimicrobial therapy has been documented to be attributable due to the development of various resistance mechanisms, with a proclivity to develop additional resistance mechanisms rapidly. P. aeruginosa virulence attenuation is an alternate technique for disrupting pathogenesis without impacting growth. The iron-scavenging siderophores (pyoverdine and pyochelin) generated by P. aeruginosa have various properties like scavenging iron, biofilm formation, quorum sensing, increasing virulence, and toxicity to the host. As a result, developing an antivirulence strategy, specifically inhibiting the P. aeruginosa siderophore, has been a promising therapeutic option to limit their infection. Several natural, synthetic compounds and nanoparticles have been identified as potent inhibitors of siderophore production/biosynthesis, function, and transport system. The current review discussed pyoverdine and pyochelin's synthesis and transport system in P. aeruginosa. Furthermore, it is also focused on the role of several natural and synthetic compounds in reducing P. aeruginosa virulence by inhibiting siderophore synthesis, function, and transport. The underlying mechanism involved in inhibiting the siderophore by natural and synthetic compounds has also been explained. KEY POINTS: ⢠Pseudomonas aeruginosa is an opportunistic pathogen linked to chronic respiratory, urinary tract, and burns infections, as well as cystic fibrosis and immunocompromised patients. ⢠P. aeruginosa produces two virulent siderophores forms: pyoverdine and pyochelin, which help it to survive in iron-deficient environments. ⢠The inhibition of siderophore production, transport, and activity using natural and synthesized drugs has been described as a potential strategy for controlling P. aeruginosa infection.
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Fibrose Cística , Sideróforos , Humanos , Pseudomonas aeruginosa , Virulência , Fibrose Cística/microbiologia , FerroRESUMO
Several studies have demonstrated that when exposed to physical, chemical, and biological stresses in the environment, many bacteria (Gram-positive and Gram-negative) change their morphology from a normal cell to a filamentous shape. The formation of filamentous morphology is one of the survival strategies against environmental stress and protection against phagocytosis or protist predators. Numerous pathogenic bacteria have shown filamentous morphologies when examined in vivo or in vitro. During infection, certain pathogenic bacteria adopt a filamentous shape inside the cell to avoid phagocytosis by immune cells. Filamentous morphology has also been seen in biofilms formed on biotic or abiotic surfaces by certain bacteria. As a result, in addition to protecting against phagocytosis by immune cells or predators, the filamentous shape aids in biofilm adhesion or colonization to biotic or abiotic surfaces. Furthermore, these filamentous morphologies of bacterial pathogens lead to antimicrobial drug resistance. Clinically, filamentous morphology has become one of the most serious challenges in treating bacterial infection. The current review went into great detail about the various factors involved in the change of filamentous morphology and the underlying mechanisms. In addition, the review discussed a control strategy for suppressing filamentous morphology in order to combat bacterial infections. Understanding the mechanism underlying the filamentous morphology induced by various environmental conditions will aid in drug development and lessen the virulence of bacterial pathogens. KEY POINTS: ⢠The bacterial filamentation morphology is one of the survival mechanisms against several environmental stress conditions and protection from phagocytosis by host cells and protist predators. ⢠The filamentous morphologies in bacterial pathogens contribute to enhanced biofilm formation, which develops resistance properties against antimicrobial drugs. ⢠Filamentous morphology has become one of the major hurdles in treating bacterial infection, hence controlling strategies employed for inhibiting the filamentation morphology from combating bacterial infections.
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Bactérias , Infecções Bacterianas , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Biofilmes , Humanos , VirulênciaRESUMO
The increased interest in nanomedicine and its applicability for a wide range of biological functions demands the search for raw materials to create nanomaterials. Recent trends have focused on the use of green chemistry to synthesize metal and metal-oxide nanoparticles. Bioactive chemicals have been found in a variety of marine organisms, including invertebrates, marine mammals, fish, algae, plankton, fungi, and bacteria. These marine-derived active chemicals have been widely used for various biological properties. Marine-derived materials, either whole extracts or pure components, are employed in the synthesis of nanoparticles due to their ease of availability, low cost of production, biocompatibility, and low cytotoxicity toward eukaryotic cells. These marine-derived nanomaterials have been employed to treat infectious diseases caused by bacteria, fungi, and viruses as well as treat non-infectious diseases, such as tumors, cancer, inflammatory responses, and diabetes, and support wound healing. Furthermore, several polymeric materials derived from the marine, such as chitosan and alginate, are exploited as nanocarriers in drug delivery. Moreover, a variety of pure bioactive compounds have been loaded onto polymeric nanocarriers and employed to treat infectious and non-infectious diseases. The current review is focused on a thorough overview of nanoparticle synthesis and its biological applications made from their entire extracts or pure chemicals derived from marine sources.
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Quitosana , Nanopartículas Metálicas , Nanopartículas , Neoplasias , Doenças não Transmissíveis , Animais , Bactérias , Quitosana/química , Sistemas de Liberação de Medicamentos , Fungos , Mamíferos , Nanopartículas Metálicas/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Doenças não Transmissíveis/tratamento farmacológico , Preparações Farmacêuticas , Polímeros/uso terapêuticoRESUMO
Phlorotannins are a group of phenolic secondary metabolites isolated from a variety of brown algal species belonging to the Fucaceae, Sargassaceae, and Alariaceae families. The isolation of phlorotannins from various algal species has received a lot of interest owing to the fact that they have a range of biological features and are very biocompatible in their applications. Phlorotannins have a wide range of therapeutic biological actions, including antimicrobial, antidiabetic, antioxidant, anticancer, anti-inflammatory, anti-adipogenesis, and numerous other biomedical applications. The current review has extensively addressed the application of phlorotannins, which have been extensively investigated for the above-mentioned biological action and the underlying mechanism of action. Furthermore, the current review offers many ways to use phlorotannins to avoid certain downsides, such as low stability. This review article will assist the scientific community in investigating the greater biological significance of phlorotannins and developing innovative techniques for treating both infectious and non-infectious diseases in humans.
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Phaeophyceae , Alga Marinha , Antioxidantes/farmacologia , Humanos , Fenóis , Taninos/farmacologia , VerdurasRESUMO
Vibrio species are motile gram-negative bacteria commonly found in aquatic environments. Vibrio species include pathogenic as well as non-pathogenic strains. Pathogenic Vibrio species have been reported in invertebrates and humans, whereas non-pathogenic strains are involved in symbiotic relationships with their eukaryotic hosts. These bacteria are also able to adapt to fluctuations in temperature, salinity, and pH, in addition to oxidative stress, and osmotic pressure in aquatic ecosystems. Moreover, they have also developed protective mechanisms against the immune systems of their hosts. Vibrio species accomplish adaptation to changing environments outside or inside the host by altering their gene expression profiles. To this end, several sigma factors specifically regulate gene expression, particularly under stressful environmental conditions. Moreover, other sigma factors are associated with biofilm formation and virulence as well. This review discusses different types of sigma and anti-sigma factors of Vibrio species involved in virulence and regulation of gene expression upon changes in environmental conditions. The evolutionary relationships between sigma factors with various physiological roles in Vibrio species are also discussed extensively.
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Fator sigma , Vibrio , Humanos , Fator sigma/genética , Fator sigma/metabolismo , Ecossistema , Vibrio/metabolismo , Estresse Oxidativo , Virulência/genética , Regulação Bacteriana da Expressão GênicaRESUMO
There is a growing interest in using sweeteners for taste improvement in the food and drink industry. Sweeteners were found to regulate the formation or dispersal of structural components of microbial biofilms. Dietary sugars may enhance biofilm formation and facilitate the development of antimicrobial resistance, which has become a major health issue worldwide. In contrast, bulk and non-nutritive sweeteners are also beneficial for managing microbial infections. This review discusses the clinical significance of oral biofilms formed upon the administration of nutritive and non-nutritive sweeteners. The underlying mechanism of action of sweeteners in the regulation of mono- or poly-microbial biofilm formation and destruction is comprehensively discussed. Bulk and non-nutritive sweeteners have also been used in conjunction with antimicrobial substances to reduce microbial biofilm formation. Formulations with bulk and non-nutritive sweeteners have been demonstrated to be particularly efficient in this regard. Finally, future perspectives with respect to advancing our understanding of mechanisms underlying biofilm regulation activities of sweeteners are presented as well. Several alternative strategies for the application of bulk sweeteners and non-nutritive sweeteners have been employed to control the biofilm-forming microbial pathogens. Gaining insight into the underlying mechanisms responsible for enhancing or inhibiting biofilm formation and virulence properties by both mono- and poly-microbial species in the presence of the sweetener is crucial for developing a therapeutic agent to manage microbial infections.
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Microbial infections are major human health issues, and, recently, the mortality rate owing to bacterial and fungal infections has been increasing. In addition to intrinsic and extrinsic antimicrobial resistance mechanisms, biofilm formation is a key adaptive resistance mechanism. Several bioactive compounds from marine organisms have been identified for use in biofilm therapy owing to their structural complexity, biocompatibility, and economic viability. In this review, we discuss recent trends in the application of marine natural compounds, marine-bioinspired nanomaterials, and marine polymer conjugates as possible therapeutic agents for controlling biofilms and virulence factors. We also comprehensively discuss the mechanisms underlying biofilm formation and inhibition of virulence factors by marine-derived materials and propose possible applications of novel and effective antibiofilm and antivirulence agents.
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This study aimed to determine enzymes that effectively extract Chlorella pyrenoidosa proteins and optimize the processing conditions using response surface methods. Furthermore, the potential of enzymatically hydrolyzed C. pyrenoidosa protein extract (CPE) as a substitute protein source was investigated. The enzymatic hydrolysis conditions for protein extraction were optimized using single-factor analysis and a response surface methodology-Box-Behnken design. The R2 value of the optimized model was 0.9270, indicating the reliability of the model, and the optimal conditions were as follows: a hydrolysis temperature of 45.56 °C, pH 9.1, and a hydrolysis time of 49.85 min. The amino acid composition of CPE was compared to that of C. pyrenoidosa powder (CP), which was found to have a higher content of essential amino acids (EAA). The electrophoretic profiles of CP and CPE confirmed that CPE has a low molecular weight. Furthermore, CPE showed higher antioxidant activity and phenol content than CP, with ABTS and DPPH radical scavenging abilities of 69.40 ± 1.61% and 19.27 ± 3.16%, respectively. CPE had high EAA content, antioxidant activity, and phenol content, indicating its potential as an alternative protein source. Overall, in this study, we developed an innovative, ecofriendly, and gentle enzymatic hydrolysis strategy for the extraction and refinement of Chlorella proteins.
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The increasing incidence of antimicrobial resistance exhibited by biofilm-forming microbial pathogens has been recognized as one of the major issues in the healthcare sector. In the present study, nanomaterial-based controlling the biofilm and virulence properties has been considered an alternative approach. Pyoverdine (PVD) isolated from the Pseudomonas aeruginosa was utilized as a biological corona to synthesize silver nanoparticles (AgNPs), which will be helpful in a targeted action to microbial pathogens due to the recognition of the corona of the nanoparticles by the pathogenic membrane. Synthesized PVD-AgNPs were spherical to irregular, with an average size value of 251.87 ± 21.8 nm and zeta potential with a value of -36.51 ± 0.69 mV. The MIC value of PVD-AgNPs towards P. aeruginosa, Listeria monocytogenes, Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Candida albicans in the standard and host-mimicking media were observed in decreasing order in a multi-fold, such as standard growth media > sputum > synthetic human urine > saliva. Both the initial stage and the well-established biofilms of these microbial pathogens have been effectively inhibited and eradicated by PVD-AgNPs. PVD-AgNPs increase the susceptibility of tetracycline, PVD, and amphotericin B towards established mature mono- and mixed-species biofilms of S. aureus and C. albicans. Additionally, PVD-AgNPs attenuate several virulence properties, such as inhibition of protease activity, motility, and PVD and pyocyanin production in P. aeruginosa. The inhibition of gene expression of biofilm and virulence-associated genes in P. aeruginosa validates its phenotypic effects.
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Pseudomonas aeruginosa is an opportunistic pathogen that produces two types of siderophores, pyoverdine and pyochelin, that play pivotal roles in iron scavenging from the environment and host cells. P. aeruginosa siderophores can serve as virulence factors and perform various functions. Several bacterial and fungal species are likely to interact with P. aeruginosa due to its ubiquity in soil and water as well as its potential to cause infections in plants, animals, and humans. Siderophores produced by P. aeruginosa play critical roles in iron scavenging for prokaryotic species (bacteria) and eukaryotic hosts (fungi, animals, insects, invertebrates, and plants) as well. This review provides a comprehensive discussion of the role of P. aeruginosa siderophores in interaction with prokaryotes and eukaryotes as well as their underlying mechanisms of action. The evolutionary relationship between P. aeruginosa siderophore recognition receptors, such as FpvA, FpvB, and FptA, and those of other bacterial species has also been investigated.
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Microbial pathogens cause persistent infections by forming biofilms and producing numerous virulence factors. Bacterial extracellular vesicles (BEVs) are nanostructures produced by various bacterial species vital for molecular transport. BEVs include various components, including lipids (glycolipids, LPS, and phospholipids), nucleic acids (genomic DNA, plasmids, and short RNA), proteins (membrane proteins, enzymes, and toxins), and quorum-sensing signaling molecules. BEVs play a major role in forming extracellular polymeric substances (EPS) in biofilms by transporting EPS components such as extracellular polysaccharides, proteins, and extracellular DNA. BEVs have been observed to carry various secretory virulence factors. Thus, BEVs play critical roles in cell-to-cell communication, biofilm formation, virulence, disease progression, and resistance to antimicrobial treatment. In contrast, BEVs have been shown to impede early-stage biofilm formation, disseminate mature biofilms, and reduce virulence. This review summarizes the current status in the literature regarding the composition and role of BEVs in microbial infections. Furthermore, the dual functions of BEVs in eliciting and suppressing biofilm formation and virulence in various microbial pathogens are thoroughly discussed. This review is expected to improve our understanding of the use of BEVs in determining the mechanism of biofilm development in pathogenic bacteria and in developing drugs to inhibit biofilm formation by microbial pathogens. STATEMENT OF SIGNIFICANCE: Bacterial extracellular vesicles (BEVs) are nanostructures formed by membrane blebbing and explosive cell lysis. It is essential for transporting lipids, nucleic acids, proteins, and quorum-sensing signaling molecules. BEVs play an important role in the formation of the biofilm's extracellular polymeric substances (EPS) by transporting its components, such as extracellular polysaccharides, proteins, and extracellular DNA. Furthermore, BEVs shield genetic material from nucleases and thermodegradation by packaging it during horizontal gene transfer, contributing to the transmission of bacterial adaptation determinants like antibiotic resistance. Thus, BEVs play a critical role in cell-to-cell communication, biofilm formation, virulence enhancement, disease progression, and drug resistance. In contrast, BEVs have been shown to prevent early-stage biofilm, disperse mature biofilm, and reduce virulence characteristics.
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Biofilmes , Ácidos Nucleicos , Humanos , Virulência , Bactérias/metabolismo , Fatores de Virulência/metabolismo , Polissacarídeos , DNA , Progressão da Doença , LipídeosRESUMO
Polymicrobial biofilms are among the leading causes of antimicrobial treatment failure. In these biofilms, bacterial and fungal pathogens interact synergistically at the interspecies, intraspecies, and interkingdom levels. Consequently, combating polymicrobial biofilms is substantially more difficult compared to single-species biofilms due to their distinct properties and the resulting potential variation in antimicrobial drug efficiency. In recent years, there has been an increased focus on developing alternative strategies for controlling polymicrobial biofilms formed by bacterial and fungal pathogens. Current approaches for controlling polymicrobial biofilms include monotherapy (using either natural or synthetic compounds), combination treatments, and nanomaterials. Here, a comprehensive review of different types of polymicrobial interactions between pathogenic bacterial species or bacteria and fungi is provided along with a discussion of their relevance. The mechanisms of action of individual compounds, combination treatments, and nanomaterials against polymicrobial biofilms are thoroughly explored. This review provides various future perspectives that can advance the strategies used to control polymicrobial biofilms and their likely modes of action. Since the majority of research on combating polymicrobial biofilms has been conducted in vitro, it would be an essential step in performing in vivo tests to determine the clinical effectiveness of different treatments against polymicrobial biofilms.
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Bactérias , Biofilmes , Biofilmes/efeitos dos fármacos , Humanos , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Fungos/fisiologia , Antibacterianos/farmacologia , Coinfecção/microbiologia , Coinfecção/tratamento farmacológico , Nanoestruturas , Interações Microbianas , Antifúngicos/farmacologiaRESUMO
Bacterial and fungal pathogens forming oral biofilms present significant public health challenges due to the failure of antimicrobial drugs. The ability of biofilms to lower pH levels results in dental plaque, leading to gingivitis and cavities. Nanoparticles (NPs) have attracted considerable interest for drug delivery and, thus, as a solution to biofilm-related microbial infections. A novel strategy in this regard involves using pH-responsive polymeric NPs within the acidic microenvironment of oral biofilms. The acidity of the oral biofilm microenvironment is governed by carbohydrate metabolism, accumulation of lactic acid, and extracellular DNA of extracellular polymeric substances by oral biofilm-forming microbial pathogens. This acidity also provides an opportunity to enhance antibacterial activity against biofilm cells using pH-responsive drug delivery approaches. Thus, various polymeric NPs loaded with poorly soluble drugs and responsive to the acidic pH of oral biofilms have been developed. This review focuses on various forms of such polymeric NPs loaded with drugs. The fundamental mechanisms of action of pH-responsive polymeric NPs, their cytological toxicity, and in vivo efficacy testing are thoroughly discussed.