Bacterial exo-polysaccharides in biofilms: role in antimicrobial resistance and treatments. - Related Documents




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915101.0000Bacterial exo-polysaccharides in biofilms: role in antimicrobial resistance and treatments. BACKGROUND: Bacterial biofilms are aggregation or collection of different bacterial cells which are covered by self-produced extracellular matrix and are attached to a substratum. Generally, under stress or in unfavorable conditions, free planktonic bacteria transform themselves into bacterial biofilms and become sessile. MAIN BODY: Various mechanisms involving interaction between antimicrobial and biofilm matrix components, reduced growth rates, and genes conferring antibiotic resistance have been described to contribute to enhanced resistance. Quorum sensing and multi-drug resistance efflux pumps are known to regulate the internal environment within the biofilm as well as biofilm formation; they also protect cells from antibiotic attack or immune attacks. This review summarizes data supporting the importance of exopolysaccharides during biofilm formation and its role in antibiotic resistance. CONCLUSIONS: Involvement of quorum sensing and efflux pumps in antibiotic resistance in association with exopolysaccharides. Also, strategies to overcome or attack biofilms are provided.202134557983
915210.9999Pseudomonas aeruginosa biofilm sensitivity to biocides: use of hydrogen peroxide as model antimicrobial agent for examining resistance mechanisms. The biofilm mode of bacterial growth may be the preferred form of existence in nature. Because of the global impact of problematic biofilms, study of the mechanisms affording resistance to various biocides is of dire importance. Furthermore, understanding the physiological differences between biofilm and planktonic organisms ranks particularly high on the list of important and necessary research. Such contributions will only serve to broaden our knowledge base, especially regarding the development of better antimicrobials while also fine-tuning the use of current highly effective antimicrobials. Using H2O2 as a model oxidizing biocide, we demonstrate the marked resistance of biofilm bacteria relative to planktonic cells. Because many biocides are good oxidizing agents (e.g., H2O2, HOCl), understanding the mechanisms by which genes involved in combating oxidative stress are activated is important in determining the overall efficacy of such biocides. Future studies will focus on determining mechanisms of oxidative stress gene regulation in bacterial biofilms.199910547822
834320.9998Bacterial Stress Responses as Potential Targets in Overcoming Antibiotic Resistance. Bacteria can be adapted to adverse and detrimental conditions that induce general and specific responses to DNA damage as well as acid, heat, cold, starvation, oxidative, envelope, and osmotic stresses. The stress-triggered regulatory systems are involved in bacterial survival processes, such as adaptation, physiological changes, virulence potential, and antibiotic resistance. Antibiotic susceptibility to several antibiotics is reduced due to the activation of stress responses in cellular physiology by the stimulation of resistance mechanisms, the promotion of a resistant lifestyle (biofilm or persistence), and/or the induction of resistance mutations. Hence, the activation of bacterial stress responses poses a serious threat to the efficacy and clinical success of antibiotic therapy. Bacterial stress responses can be potential targets for therapeutic alternatives to antibiotics. An understanding of the regulation of stress response in association with antibiotic resistance provides useful information for the discovery of novel antimicrobial adjuvants and the development of effective therapeutic strategies to control antibiotic resistance in bacteria. Therefore, this review discusses bacterial stress responses linked to antibiotic resistance in Gram-negative bacteria and also provides information on novel therapies targeting bacterial stress responses that have been identified as potential candidates for the effective control of Gram-negative antibiotic-resistant bacteria.202235889104
942930.9998Basic features of biofilms--why are they difficult therapeutic targets? The purpose of this paper is to review the basic features of biofilms associated with human infections and summarize why such biofilms are resistant to antimicrobial agents. The formation of most biofilms involves adherence of bacteria to a conditioned surface, growth and division of the attached bacteria, synthesis of a polymeric slime matrix, formation of a structured microbial community, and incorporation of other micro-organisms into the microbial mass. The transition of bacteria from free-floating (planktonic) to biofilm environments involves extensive up-regulation of genes associated with adherence. Micro-organisms in established biofilms engage in complex integrated activities involving activation and deactivation of genes that promote the survival of bacteria within the biofilm community. Mechanisms of the increased resistance of biofilm bacteria to antimicrobial agents may involve: (1) neutralization or consumption of the drug, (2) failure of the drug to completely penetrate the biofilm, (3) inability of the drug to affect metabolically inactive bacteria, and (4) presence of drug-resistant bacteria within biofilms.200416479852
942740.9998Polysaccharides' Structures and Functions in Biofilm Architecture of Antimicrobial-Resistant (AMR) Pathogens. Bacteria and fungi have developed resistance to the existing therapies such as antibiotics and antifungal drugs, and multiple mechanisms are mediating this resistance. Among these, the formation of an extracellular matrix embedding different bacterial cells, called biofilm, is an effective strategy through which bacterial and fungal cells are establishing a relationship in a unique environment. The biofilm provides them the possibility to transfer genes conferring resistance, to prevent them from desiccation and to impede the penetration of antibiotics or antifungal drugs. Biofilms are formed of several constituents including extracellular DNA, proteins and polysaccharides. Depending on the bacteria, different polysaccharides form the biofilm matrix in different microorganisms, some of them involved in the first stage of cells' attachment to surfaces and to each other, and some responsible for giving the biofilm structure resistance and stability. In this review, we describe the structure and the role of different polysaccharides in bacterial and fungal biofilms, we revise the analytical methods to characterize them quantitatively and qualitatively and finally we provide an overview of potential new antimicrobial therapies able to inhibit biofilm formation by targeting exopolysaccharides.202336835442
943050.9998Mechanisms of antimicrobial resistance in biofilms. Most bacteria in nature exist in aggregated communities known as biofilms, and cells within a biofilm demonstrate major physiological changes compared to their planktonic counterparts. Biofilms are associated with many different types of infections which can have severe impacts on patients. Infections involving a biofilm component are often chronic and highly recalcitrant to antibiotic therapy as a result of intrinsic physical factors including extracellular matrix production, low growth rates, altered antibiotic target production and efficient exchange of resistance genes. This review describes the biofilm lifecycle, phenotypic characteristics of a biofilm, and contribution of matrix and persister cells to biofilms intrinsic tolerance to antimicrobials. We also describe how biofilms can evolve antibiotic resistance and transfer resistance genes within biofilms. Multispecies biofilms and the impacts of various interactions, including cooperation and competition, between species on tolerance to antimicrobials in polymicrobial biofilm communities are also discussed.202439364333
834260.9998Inflammatory immunity and bacteriological perspectives: A new direction for copper treatment of sepsis. Copper is an essential trace element for all aerobic organisms because of its unique biological functions. In recent years, researchers have discovered that copper can induce cell death through various regulatory mechanisms, thereby inducing inflammation. Efforts have also been made to alter the chemical structure of copper to achieve either anticancer or anti-inflammatory effects. The copper ion can exhibit bactericidal effects by interfering with the integrity of the cell membrane and promoting oxidative stress. Sepsis is a systemic inflammatory response caused by infection. Some studies have revealed that copper is involved in the pathophysiological process of sepsis and is closely related to its prognosis. During the infection of sepsis, the body may enhance the antimicrobial effect by increasing the release of copper. However, to avoid copper poisoning, all organisms have evolved copper resistance genes. Therefore, further analysis of the complex relationship between copper and bacteria may provide new ideas and research directions for the treatment of sepsis.202438692229
917170.9998Small molecules modulating AHL-based quorum sensing to attenuate bacteria virulence and biofilms as promising antimicrobial drugs. Clinically significant antibiotic resistance is one of the greatest challenges of the twenty-first century. Yet new antibiotics are currently being developed at a much slower pace than our growing need for such drugs. Instead of focusing on conventional therapeutics that target in vitro bacterial viability, an alternative therapy is to target virulence factors and biofilms. Such anti-virulence strategies have attracted more and more attention recently, for it would add both supplement and diversity to our current antimicrobial library. This approach has several potential advantages including imposing less evolutionary pressure on the development of antibiotic resistance, increasing the antibacterial targets and preserving the host endogenous microbiome. Quorum sensing is an intercellular communication process in bacterial communities, which can regulate coordinated expression of virulence factors and biofilms. N-Acyl homoserine lactones (AHLs) are autoinducers generated by a variety of Gram-negative bacteria. These signals combining with their cognate LuxR-type receptors trigger the expression of virulence genes. In this critical review, we summarize various structural types of small molecules targeting AHL-based quorum sensing to attenuate bacteria virulence factors and biofilms.201424164200
824280.9998New antibacterial targets: Regulation of quorum sensing and secretory systems in zoonotic bacteria. Quorum sensing (QS) is a communication mechanism that controls bacterial communication and can influence the transcriptional expression of multiple genes through one or more signaling molecules, thereby coordinating the population response of multiple bacterial pathogens. Secretion systems (SS) play an equally important role in bacterial information exchange, relying on the secretory systems to secrete proteins that act as virulence factors to promote adhesion to host cells. Eight highly efficient SS have been described, all of which are involved in the secretion or transfer of virulence factors, and the effector proteins they secrete play a key role in the virulence and pathogenicity of bacteria. It has been shown that many bacterial SS are directly or indirectly regulated by QS and thus influence bacterial virulence and antibiotic resistance. This review describes the relationship between QS and SS of several common zoonotic pathogenic bacteria and outlines the molecular mechanisms of how QS systems regulate SS, to provide a theoretical basis for the study of bacterial pathogenicity and the development of novel antibacterial drugs.202337343493
914890.9998Biofilms as Battlefield Armor for Bacteria against Antibiotics: Challenges and Combating Strategies. Bacterial biofilms are formed by communities, which are encased in a matrix of extracellular polymeric substances (EPS). Notably, bacteria in biofilms display a set of 'emergent properties' that vary considerably from free-living bacterial cells. Biofilms help bacteria to survive under multiple stressful conditions such as providing immunity against antibiotics. Apart from the provision of multi-layered defense for enabling poor antibiotic absorption and adaptive persistor cells, biofilms utilize their extracellular components, e.g., extracellular DNA (eDNA), chemical-like catalase, various genes and their regulators to combat antibiotics. The response of biofilms depends on the type of antibiotic that comes into contact with biofilms. For example, excessive production of eDNA exerts resistance against cell wall and DNA targeting antibiotics and the release of antagonist chemicals neutralizes cell membrane inhibitors, whereas the induction of protein and folic acid antibiotics inside cells is lowered by mutating genes and their regulators. Here, we review the current state of knowledge of biofilm-based resistance to various antibiotic classes in bacteria and genes responsible for biofilm development, and the key role of quorum sensing in developing biofilms and antibiotic resistance is also discussed. In this review, we also highlight new and modified techniques such as CRISPR/Cas, nanotechnology and bacteriophage therapy. These technologies might be useful to eliminate pathogens residing in biofilms by combating biofilm-induced antibiotic resistance and making this world free of antibiotic resistance.202337894253
9169100.9998Interference of bacterial cell-to-cell communication: a new concept of antimicrobial chemotherapy breaks antibiotic resistance. Bacteria use a cell-to-cell communication activity termed "quorum sensing" to coordinate group behaviors in a cell density dependent manner. Quorum sensing influences the expression profile of diverse genes, including antibiotic tolerance and virulence determinants, via specific chemical compounds called "autoinducers". During quorum sensing, Gram-negative bacteria typically use an acylated homoserine lactone (AHL) called autoinducer 1. Since the first discovery of quorum sensing in a marine bacterium, it has been recognized that more than 100 species possess this mechanism of cell-to-cell communication. In addition to being of interest from a biological standpoint, quorum sensing is a potential target for antimicrobial chemotherapy. This unique concept of antimicrobial control relies on reducing the burden of virulence rather than killing the bacteria. It is believed that this approach will not only suppress the development of antibiotic resistance, but will also improve the treatment of refractory infections triggered by multi-drug resistant pathogens. In this paper, we review and track recent progress in studies on AHL inhibitors/modulators from a biological standpoint. It has been discovered that both natural and synthetic compounds can disrupt quorum sensing by a variety of means, such as jamming signal transduction, inhibition of signal production and break-down and trapping of signal compounds. We also focus on the regulatory elements that attenuate quorum sensing activities and discuss their unique properties. Understanding the biological roles of regulatory elements might be useful in developing inhibitor applications and understanding how quorum sensing is controlled.201323720655
9542110.9998Development of quorum-based anti-virulence therapeutics targeting Gram-negative bacterial pathogens. Quorum sensing is a cell density-dependent signaling phenomenon used by bacteria for coordination of population-wide phenotypes, such as expression of virulence genes, antibiotic resistance and biofilm formation. Lately, disruption of bacterial communication has emerged as an anti-virulence strategy with enormous therapeutic potential given the increasing incidences of drug resistance in pathogenic bacteria. The quorum quenching therapeutic approach promises a lower risk of resistance development, since interference with virulence generally does not affect the growth and fitness of the bacteria and, hence, does not exert an associated selection pressure for drug-resistant strains. With better understanding of bacterial communication networks and mechanisms, many quorum quenching methods have been developed against various clinically significant bacterial pathogens. In particular, Gram-negative bacteria are an important group of pathogens, because, collectively, they are responsible for the majority of hospital-acquired infections. Here, we discuss the current understanding of existing quorum sensing mechanisms and present important inhibitory strategies that have been developed against this group of pathogenic bacteria.201323939429
9146120.9998Emergence of microbial resistance against nanoparticles: Mechanisms and strategies. Antimicrobial nanoparticles have gained the status of a new generation of drugs that can kill bacterial pathogens by multiple means; however, nanoparticle resistance acquired by some bacterial pathogens has evoked a cause of concern. Several reports suggested that bacteria can develop nanoparticles, specifically metal nanoparticle resistance, by mechanisms: nanoparticle transformation-induced oxidative stress, membrane alterations, reversible adaptive resistance, irreversible modifications to cell division, and a change in bacterial motility and resistance. Surface properties, concentration and aggregation of nanoparticles, biofilm forming and metal exclusion capacity, and R plasmid and flagellin synthesis by bacteria are crucial factors in the development of nanoparticle resistance in bacteria. Studies reported the resistance reversal by modifying the surface corona of nanoparticles or inhibiting flagellin production by bacterial pathogens. Furthermore, strict regulation regarding the use and disposal of nano-waste across the globe, the firm knowledge of microbe-nanoparticle interaction, and the regulated disposal of nanoparticles in soil and water is required to prevent microbes from developing nanoparticle resistance.202336778867
9137130.9998Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy. Two-component signal transduction systems are central elements of the virulence and antibiotic resistance responses of opportunistic bacterial pathogens. These systems allow the bacterium to sense and respond to signals emanating from the host environment and to modulate the repertoire of genes expressed to allow invasion and growth in the host. The integral role of two-component systems in virulence and antibiotic sensitivity, and the existence of essential two-component systems in several pathogenic bacteria, suggests that these systems may be novel targets for antimicrobial intervention. This review discusses the potential use of two-component systems as targets for antimicrobial therapy against Gram-positive pathogens and the current status in the development of inhibitors specific for these systems.200212191621
9170140.9998It is the time for quorum sensing inhibition as alternative strategy of antimicrobial therapy. Multiple drug resistance poses a significant threat to public health worldwide, with a substantial increase in morbidity and mortality rates. Consequently, searching for novel strategies to control microbial pathogenicity is necessary. With the aid of auto-inducers (AIs), quorum sensing (QS) regulates bacterial virulence factors through cell-to-cell signaling networks. AIs are small signaling molecules produced during the stationary phase. When bacterial cultures reach a certain level of growth, these molecules regulate the expression of the bound genes by acting as mirrors that reflect the inoculum density.Gram-positive bacteria use the peptide derivatives of these signaling molecules, whereas Gram-negative bacteria use the fatty acid derivatives, and the majority of bacteria can use both types to modulate the expression of the target gene. Numerous natural and synthetic QS inhibitors (QSIs) have been developed to reduce microbial pathogenesis. Applications of QSI are vital to human health, as well as fisheries and aquaculture, agriculture, and water treatment. Video Abstract.202337316831
8284150.9998Redox signaling in human pathogens. In recent studies of human bacterial pathogens, oxidation sensing and regulation have been shown to impact very diverse pathways that extend beyond inducing antioxidant genes in the bacteria. In fact, some redox-sensitive regulatory proteins act as major regulators of bacteria's adaptability to oxidative stress, an ability that originates from immune host response as well as antibiotic stress. Such proteins play particularly important roles in pathogenic bacteria S. aureus, P. aeruginosa, and M. tuberculosis in part because reactive oxygen species and reactive nitrogen species present significant challenges for pathogens during infection. Herein, we review recent progress toward the identification and understanding of oxidation sensing and regulation in human pathogens. The newly identified redox switches in pathogens are a focus of this review. We will cover several reactive oxygen species-sensing global regulators in both gram-positive and gram-negative pathogenic bacteria in detail. The following discussion of the mechanisms that these proteins employ to sense redox signals through covalent modification of redox active amino acid residues or associated metalloprotein centers will provide further understanding of bacteria pathogenesis, antibiotic resistance, and host-pathogen interaction.201120578795
9150160.9998Microbial silver resistance mechanisms: recent developments. In this mini-review, after a brief introduction into the widespread antimicrobial use of silver ions and nanoparticles against bacteria, fungi and viruses, the toxicity of silver compounds and the molecular mechanisms of microbial silver resistance are discussed, including recent studies on bacteria and fungi. The similarities and differences between silver ions and silver nanoparticles as antimicrobial agents are also mentioned. Regarding bacterial ionic silver resistance, the roles of the sil operon, silver cation efflux proteins, and copper-silver efflux systems are explained. The importance of bacterially produced exopolysaccharides as a physiological (biofilm) defense mechanism against silver nanoparticles is also emphasized. Regarding fungal silver resistance, the roles of metallothioneins, copper-transporting P-type ATPases and cell wall are discussed. Recent evolutionary engineering (adaptive laboratory evolution) studies are also discussed which revealed that silver resistance can evolve rapidly in bacteria and fungi. The cross-resistance observed between silver resistance and resistance to other heavy metals and antibiotics in bacteria and fungi is also explained as a clinically and environmentally important issue. The use of silver against bacterial and fungal biofilm formation is also discussed. Finally, the antiviral effects of silver and the use of silver nanoparticles against SARS-CoV-2 and other viruses are mentioned. To conclude, silver compounds are becoming increasingly important as antimicrobial agents, and their widespread use necessitates detailed understanding of microbial silver response and resistance mechanisms, as well as the ecological effects of silver compounds. Figure created with BioRender.com.202235821348
8285170.9998Bacterial stress response: understanding the molecular mechanics to identify possible therapeutic targets. INTRODUCTION: Bacteria are ubiquitous and many of them are pathogenic in nature. Entry of bacteria in host and its recognition by host defense system induce stress in host cells. With time, bacteria have also developed strategies including drug resistance to escape from antibacterial therapy as well as host defense mechanism. AREAS COVERED: Bacterial stress initiates and promotes adaptive immune response through several integrated mechanisms. The mechanisms of bacteria to up and down regulate different pathways involved in these responses have been discussed. The genetic expression of these pathways can be manipulated by the pharmacological interventions. Present review discusses in these contexts and explores the possibilities to overcome stress induced by bacterial pathogens and to suggest new possible therapeutic targets. EXPERT OPINION: In our opinion, there are two important fronts to regulate the bacterial stress. One is to target caspase involved in the process of transformation and translation at gene level and protein expression. Second is the identification of bacterial genes that lead to synthesis of abnormal end products supporting bacterial survival in host environment and also to surpass the host defense mechanism. Identification of such genes and their expression products could be an effective option to encounter bacterial resistance.202132811215
8241180.9998Molecular mechanisms of N-acyl homoserine lactone signals perception by plants. N-acyl homoserine lactones (AHLs) belong to the class of bacterial quorum sensing signal molecules involved in distance signal transduction between Gram-negative bacteria colonizers of the rhizosphere, as well as bacteria and plants. AHLs synchronize the activity of genes from individual cells, allowing the bacterial population to act as a multicellular organism, and establish a symbiotic or antagonistic relationship with the host plant. Although the effect of AHLs on plants has been studied for more than ten years, the mechanisms of plant perception of AHL signals are not fully understood. The specificity of the reactions caused by AHL indicates the existence of appropriate mechanisms for their perception by plants. In the current review, we summarize available data on the molecular mechanisms of AHL-signal perception in plants, its effect on plant growth, development, and stress resistance. We describe the latest research demonstrating direct (on plants) and indirect (on rhizosphere microflora) effects of AHLs, as well as the prospects of using these compounds in biotechnology to increase plant resistance to biotic and abiotic stresses.202234937124
9140190.9997Polyamine as a microenvironment factor in resistance to antibiotics. One of the main issues in modern medicine is the decrease in the efficacy of antibiotic therapy against resistant microorganisms. The advent of antimicrobial resistance has added significantly to the impact of infectious diseases, in number of infections, as well as added healthcare costs. The development of antibiotic tolerance and resistance is influenced by a variety of environmental variables, and it is important to identify these environmental factors as part of any strategy for combating antibiotic resistance. The review aims to emphasize that biogenic polyamines are one of such environmental cues that impacts the antibiotic resistance in bacteria. The biogenic polyamines can help bacteria acquire resistance to antibiotics either by regulating the level of number of porin channels in the outer membrane, by modifying the outer membrane liposaccharides or by protecting macromolecule from antibiotic stress. Thus, understanding the way polyamines function in bacteria can thus be beneficial while designing the drugs to combat diseases.202437339480