Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies.
TL;DR: Novel strategies that specifically target the biofilm mode of growth have been recently described, thus providing the basis for future anti-biofilm therapy.
About: This article is published in Current Opinion in Microbiology.The article was published on 2013-10-01. It has received 626 citations till now. The article focuses on the topics: Biofilm.
Citations
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TL;DR: CRISPR-CAS (gene editing technique) and photo dynamic therapy (PDT) are proposed to be used as therapeutic approaches to subside bacterial biofim infections, especially caused by deadly drug resistant bad bugs.
Abstract: Biofilm is a complex structure of microbiome having different bacterial colonies or single type of cells in a group; adhere to the surface. These cells are embedded in extracellular polymeric substances, a matrix which is generally composed of eDNA, proteins and polysaccharides, showed high resistance to antibiotics. It is one of the major causes of infection persistence especially in nosocomial settings through indwelling devices. Quorum sensing plays an important role in regulating the biofilm formation. There are many approaches being used to control infections by suppressing its formation but CRISPR-CAS (gene editing technique) and photo dynamic therapy (PDT) are proposed to be used as therapeutic approaches to subside bacterial biofim infections, especially caused by deadly drug resistant bad bugs.
726 citations
Cites background from "Bacterial biofilm development as a ..."
...Bacterial biofilms are serious global health concern due to their abilities to tolerate antibiotics, host defence systems and other external stresses; therefore it contributes to persistent chronic infections [27, 33]....
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TL;DR: An efficient treatment ofBiofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.
Abstract: Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.
678 citations
University of Leicester1, University of Hertfordshire2, Rockefeller University3, University of Sheffield4, Queen's University Belfast5, University of British Columbia6, University of Bedfordshire7, University of Birmingham8, St George's, University of London9, University of Brighton10, Queen Victoria Hospital11, University of Liverpool12, Norwich University13, GlaxoSmithKline14, MedImmune15, Imperial College London16, AstraZeneca17
TL;DR: This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed.
Abstract: Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future.
640 citations
TL;DR: The current understanding of the pathways behind biofilm dispersal in S. aureus is discussed, with a focus on enzymatic and newly described broad-spectrum dispersal mechanisms, and potential applications in the treatment of biofilm-mediated infections.
Abstract: Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and represents a significant burden on the healthcare system. S. aureus attachment to medical implants and host tissue, and the establishment of a mature biofilm, play an important role in the persistence of chronic infections. The formation of a biofilm, and encasement of cells in a polymer-based matrix, decreases the susceptibility to antimicrobials and immune defenses, making these infections difficult to eradicate. During infection, dispersal of cells from the biofilm can result in spread to secondary sites and worsening of the infection. In this review, we discuss the current understanding of the pathways behind biofilm dispersal in S. aureus, with a focus on enzymatic and newly described broad-spectrum dispersal mechanisms. Additionally, we explore potential applications of dispersal in the treatment of biofilm-mediated infections.
451 citations
Cites background from "Bacterial biofilm development as a ..."
...Additionally, biofilm cells display increased tolerance to antibiotics (de la Fuente-Nunez et al., 2013)....
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TL;DR: As de facto determinants of antimicrobial, even multidrug, resistance, stress responses may be worthy of consideration as therapeutic targets.
Abstract: Bacteria encounter a myriad of stresses in their natural environments, including, for pathogens, their hosts. These stresses elicit a variety of specific and highly regulated adaptive responses that not only protect bacteria from the offending stress, but also manifest changes in the cell that impact innate antimicrobial susceptibility. Thus exposure to nutrient starvation/limitation (nutrient stress), reactive oxygen and nitrogen species (oxidative/nitrosative stress), membrane damage (envelope stress), elevated temperature (heat stress) and ribosome disruption (ribosomal stress) all impact bacterial susceptibility to a variety of antimicrobials through their initiation of stress responses that positively impact recruitment of resistance determinants or promote physiological changes that compromise antimicrobial activity. As de facto determinants of antimicrobial, even multidrug, resistance, stress responses may be worthy of consideration as therapeutic targets.
437 citations
References
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TL;DR: Improvements in understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
Abstract: Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
11,162 citations
"Bacterial biofilm development as a ..." refers background in this paper
...It is estimated that the majority of all medical infections are caused by bacterial biofilms that colonize either nonbiological or biological surfaces [2,13 ,14] (Table 1)....
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...com processes, especially a decline in metabolism in bacteria deeper in the biofilm structure [1,2,3,10]....
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...aeruginosa and a plethora of other environmental bacteria that opportunistically infect hosts compromised by invasive medical intervention, chemotherapy or a pre-existing disease state [1,2,13 ,14]....
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...Mature biofilms eventually form and include prominent microcolonies that protrude from the surface, are held together by molecules termed collectively the extracellular matrix, including specific polysaccharides, proteins, and extracellular DNA (eDNA) [9], and contain water-filled channels enabling enhanced access of nutrients into the biofilm [1,2,10]....
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...Initially this might be a response to association with a surface, which can occur through adhesion organelles including pili, flagella and external microbial layers, or due to immobilization of the bacteria [2,3,7]....
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TL;DR: The functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth are described.
Abstract: The microorganisms in biofilms live in a self-produced matrix of hydrated extracellular polymeric substances (EPS) that form their immediate environment. EPS are mainly polysaccharides, proteins, nucleic acids and lipids; they provide the mechanical stability of biofilms, mediate their adhesion to surfaces and form a cohesive, three-dimensional polymer network that interconnects and transiently immobilizes biofilm cells. In addition, the biofilm matrix acts as an external digestive system by keeping extracellular enzymes close to the cells, enabling them to metabolize dissolved, colloidal and solid biopolymers. Here we describe the functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth.
7,041 citations
"Bacterial biofilm development as a ..." refers background in this paper
...com processes, especially a decline in metabolism in bacteria deeper in the biofilm structure [1,2,3,10]....
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...Typically, the cells in a biofilm are embedded in a matrix of polysaccharides, extracellular DNA (eDNA) and proteins [10]....
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...Mature biofilms eventually form and include prominent microcolonies that protrude from the surface, are held together by molecules termed collectively the extracellular matrix, including specific polysaccharides, proteins, and extracellular DNA (eDNA) [9], and contain water-filled channels enabling enhanced access of nutrients into the biofilm [1,2,10]....
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TL;DR: It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments.
Abstract: Biofilms--matrix-enclosed microbial accretions that adhere to biological or non-biological surfaces--represent a significant and incompletely understood mode of growth for bacteria. Biofilm formation appears early in the fossil record (approximately 3.25 billion years ago) and is common throughout a diverse range of organisms in both the Archaea and Bacteria lineages, including the 'living fossils' in the most deeply dividing branches of the phylogenetic tree. It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments. Recent advances show that biofilms are structurally complex, dynamic systems with attributes of both primordial multicellular organisms and multifaceted ecosystems. Biofilm formation represents a protected mode of growth that allows cells to survive in hostile environments and also disperse to colonize new niches. The implications of these survival and propagative mechanisms in the context of both the natural environment and infectious diseases are discussed in this review.
6,170 citations
"Bacterial biofilm development as a ..." refers background in this paper
...com processes, especially a decline in metabolism in bacteria deeper in the biofilm structure [1,2,3,10]....
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...From a broader perspective, biofilms are ancient phenotypic adaptations to the environment and are ubiquitous in Nature [1]....
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...aeruginosa and a plethora of other environmental bacteria that opportunistically infect hosts compromised by invasive medical intervention, chemotherapy or a pre-existing disease state [1,2,13 ,14]....
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...Biofilm formation in Nature and in the clinic Biofilms are formed in diverse environmental niches, including hydrothermal hot springs and deep-sea vents, freshwater rivers, rocks, etc. [1,2]....
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...Nature 2001, 413:860-864....
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TL;DR: The role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
Abstract: Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
3,556 citations
"Bacterial biofilm development as a ..." refers background in this paper
...Similar peptides have also been shown to exhibit immunomodulatory and anti-inflammatory activities [54], although it has not been established if this is an additional property of these peptides (except LL-37)....
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TL;DR: The involvement of an intercellular signal molecule in the development of Pseudomonas aeruginosa biofilms suggests possible targets to control biofilm growth on catheters, in cystic fibrosis, and in other environments where P. aerug inosaBiofilms are a persistent problem.
Abstract: Bacteria in nature often exist as sessile communities called biofilms. These communities develop structures that are morphologically and physiologically differentiated from free-living bacteria. A cell-to-cell signal is involved in the development of Pseudomonas aeruginosa biofilms. A specific signaling mutant, a lasI mutant, forms flat, undifferentiated biofilms that unlike wild-type biofilms are sensitive to the biocide sodium dodecyl sulfate. Mutant biofilms appeared normal when grown in the presence of a synthetic signal molecule. The involvement of an intercellular signal molecule in the development of P. aeruginosa biofilms suggests possible targets to control biofilm growth on catheters, in cystic fibrosis, and in other environments where P. aeruginosa biofilms are a persistent problem.
3,335 citations
"Bacterial biofilm development as a ..." refers background in this paper
...One such signal molecule is the quorum-sensing signal 3-oxo-C12homoserine lactone of Pseudomonas aeruginosa, which is required for the efficient differentiation of planktonic into biofilm cells [8]....
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