scholarly journals Exosome-associated host–pathogen interaction: a potential effect of biofilm formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dibyajit Lahiri ◽  
Moupriya Nag ◽  
Ankita Dey ◽  
Tanmay Sarkar ◽  
Smaranika Pattnaik ◽  
...  

AbstractExosomes being non-ionized micro-vesicles with a size range of 30–100 nm possess the ability to bring about intracellular communication and intercellular transport of various types of cellular components like miRNA, mRNA, DNA, and proteins. This is achieved through the targeted transmission of various inclusions to nearby or distant tissues. This is associated with the effective communication of information to bring about changes in physiological properties and functional attributes. The extracellular vesicles (EVs), produced by fungi, parasites, and bacteria, are responsible to bring about modulation/alteration of the immune responses exerted by the host body. The lipids, nucleic acids, proteins, and glycans of EVs derived from the pathogens act as the ligands of different families of pattern recognition receptors of the host body. The bacterial membrane vesicles (BMVs) are responsible for the transfer of small RNA species, along with other types of noncoding RNA thereby playing a key role in the regulation of the host immune system. Apart from immunomodulation, the BMVs are also responsible for bacterial colonization in the host tissue, biofilm formation, and survival therein showing antibiotic resistance, leading to pathogenesis and virulence. This mini-review would focus on the role of exosomes in the development of biofilm and consequent immunological responses within the host body along with an analysis of the mechanism associated with the development of resistance.

2021 ◽  
Vol 15 ◽  
pp. 117793222110258
Author(s):  
Ritesh Gorkhali ◽  
Prashanna Koirala ◽  
Sadikshya Rijal ◽  
Ashmita Mainali ◽  
Adesh Baral ◽  
...  

SARS-CoV-2 virus, the causative agent of COVID-19 pandemic, has a genomic organization consisting of 16 nonstructural proteins (nsps), 4 structural proteins, and 9 accessory proteins. Relative of SARS-CoV-2, SARS-CoV, has genomic organization, which is very similar. In this article, the function and structure of the proteins of SARS-CoV-2 and SARS-CoV are described in great detail. The nsps are expressed as a single or two polyproteins, which are then cleaved into individual proteins using two proteases of the virus, a chymotrypsin-like protease and a papain-like protease. The released proteins serve as centers of virus replication and transcription. Some of these nsps modulate the host’s translation and immune systems, while others help the virus evade the host immune system. Some of the nsps help form replication-transcription complex at double-membrane vesicles. Others, including one RNA-dependent RNA polymerase and one exonuclease, help in the polymerization of newly synthesized RNA of the virus and help minimize the mutation rate by proofreading. After synthesis of the viral RNA, it gets capped. The capping consists of adding GMP and a methylation mark, called cap 0 and additionally adding a methyl group to the terminal ribose called cap1. Capping is accomplished with the help of a helicase, which also helps remove a phosphate, two methyltransferases, and a scaffolding factor. Among the structural proteins, S protein forms the receptor of the virus, which latches on the angiotensin-converting enzyme 2 receptor of the host and N protein binds and protects the genomic RNA of the virus. The accessory proteins found in these viruses are small proteins with immune modulatory roles. Besides functions of these proteins, solved X-ray and cryogenic electron microscopy structures related to the function of the proteins along with comparisons to other coronavirus homologs have been described in the article. Finally, the rate of mutation of SARS-CoV-2 residues of the proteome during the 2020 pandemic has been described. Some proteins are mutated more often than other proteins, but the significance of these mutation rates is not fully understood.


2021 ◽  
Vol 10 (8) ◽  
pp. 1641
Author(s):  
Stefanie Kligman ◽  
Zhi Ren ◽  
Chun-Hsi Chung ◽  
Michael Angelo Perillo ◽  
Yu-Cheng Chang ◽  
...  

Implant surface design has evolved to meet oral rehabilitation challenges in both healthy and compromised bone. For example, to conquer the most common dental implant-related complications, peri-implantitis, and subsequent implant loss, implant surfaces have been modified to introduce desired properties to a dental implant and thus increase the implant success rate and expand their indications. Until now, a diversity of implant surface modifications, including different physical, chemical, and biological techniques, have been applied to a broad range of materials, such as titanium, zirconia, and polyether ether ketone, to achieve these goals. Ideal modifications enhance the interaction between the implant’s surface and its surrounding bone which will facilitate osseointegration while minimizing the bacterial colonization to reduce the risk of biofilm formation. This review article aims to comprehensively discuss currently available implant surface modifications commonly used in implantology in terms of their impact on osseointegration and biofilm formation, which is critical for clinicians to choose the most suitable materials to improve the success and survival of implantation.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Poushali Chakraborty ◽  
Sapna Bajeli ◽  
Deepak Kaushal ◽  
Bishan Dass Radotra ◽  
Ashwani Kumar

AbstractTuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.


2019 ◽  
Vol 98 (7) ◽  
pp. 739-745 ◽  
Author(s):  
C. Cugini ◽  
M. Shanmugam ◽  
N. Landge ◽  
N. Ramasubbu

The oral cavity contains a rich consortium of exopolysaccharide-producing microbes. These extracellular polysaccharides comprise a major component of the oral biofilm. Together with extracellular proteins, DNA, and lipids, they form the biofilm matrix, which contributes to bacterial colonization, biofilm formation and maintenance, and pathogenesis. While a number of oral microbes have been studied in detail with regard to biofilm formation and pathogenesis, the exopolysaccharides have been well characterized for only select organisms, namely Streptococcus mutans and Aggregatibacter actinomycetemcomitans. Studies on the exopolysaccharides of other oral organisms, however, are in their infancy. In this review, we present the current research on exopolysaccharides of oral microbes regarding their biosynthesis, regulation, contributions to biofilm formation and stability of the matrix, and immune evasion. In addition, insight into the role of exopolysaccharides in biofilms is highlighted through the evaluation of emerging techniques such as pH probing of biofilm colonies, solid-state nuclear magnetic resonance for macromolecular interactions within biofilms, and super-resolution microscopy analysis of biofilm development. Finally, exopolysaccharide as a potential nutrient source for species within a biofilm is discussed.


2012 ◽  
Vol 80 (6) ◽  
pp. 1948-1957 ◽  
Author(s):  
Brooke L. Deatherage ◽  
Brad T. Cookson

ABSTRACTInteraction of microbes with their environment depends on features of the dynamic microbial surface throughout cell growth and division. Surface modifications, whether used to acquire nutrients, defend against other microbes, or resist the pressures of a host immune system, facilitate adaptation to unique surroundings. The release of bioactive membrane vesicles (MVs) from the cell surface is conserved across microbial life, in bacteria, archaea, fungi, and parasites. MV production occurs not onlyin vitrobut alsoin vivoduring infection, underscoring the influence of these surface organelles in microbial physiology and pathogenesis through delivery of enzymes, toxins, communication signals, and antigens recognized by the innate and adaptive immune systems. Derived from a variety of organisms that span kingdoms of life and called by several names (membrane vesicles, outer membrane vesicles [OMVs], exosomes, shedding microvesicles, etc.), the conserved functions and mechanistic strategies of MV release are similar, including the use of ESCRT proteins and ESCRT protein homologues to facilitate these processes in archaea and eukaryotic microbes. Although forms of MV release by different organisms share similar visual, mechanistic, and functional features, there has been little comparison across microbial life. This underappreciated conservation of vesicle release, and the resulting functional impact throughout the tree of life, explored in this review, stresses the importance of vesicle-mediated processes throughout biology.


2021 ◽  
pp. 088532822110511
Author(s):  
Youbin Li ◽  
Shaochuan Wang ◽  
Shidan Li ◽  
Jun Fei

Implant-related infection is a disastrous complication. Surface modification of titanium is considered as an important strategy to prevent implant-related infection. However, there is no recognized surface modification strategy that can be applied in clinic so far. We explored a new strategy of coating. The clindamycin-loaded titanium was constructed by layer-by-layer self-assembly. The release of clindamycin from titanium was detected through high performance liquid chromatography. Different titanium was co-cultured with Staphylococcus aureus for 24 h in vitro, then the effect of different titanium on bacterial colonization and biofilm formation was determined by spread plate method and scanning electron microscopy. Cytotoxicity and cytocompatibility of clindamycin-loaded titanium on MC3T3-E1 cells were measured by CCK8. The antibacterial ability of clindamycin-loaded titanium in vivo was also evaluated using a rat model of osteomyelitis. The number of osteoclasts in bone defect was observed by tartrate-resistant acid phosphatase staining. Bacterial burden of surrounding tissues around the site of infection was calculated by tissue homogenate and colony count. Clindamycin-loaded titanium could release clindamycin slowly within 160 h. It reduced bacterial colonization by three orders of magnitude compare to control ( p < .05) and inhibits biofilm formation in vitro. Cells proliferation and adhesion were similar on three titanium surfaces ( p > .05). In vivo, clindamycin-loaded titanium improved bone healing, reduced microbial burden, and decreased the number of osteoclasts compared control titanium in the rat model of osteomyelitis. This study demonstrated that clindamycin-loaded titanium exhibited good biocompatibility, and showed antibacterial activity both in vivo and in vitro. It is promising and might have potential for clinical application.


2019 ◽  
Vol 18 (24) ◽  
pp. 2068-2079 ◽  
Author(s):  
Michele Ciulla ◽  
Antonio Di Stefano ◽  
Lisa Marinelli ◽  
Ivana Cacciatore ◽  
Giuseppe Di Biase

S. aureus under the biofilm mode of growth is often related to several nosocomial infections, more frequently associated with indwelling medical devices (catheters, prostheses, portacaths or heart valves). As a biofilm, the biopolymer matrix provides an excellent growth medium, increasing the tolerance to antibiotics and host immune system. To date, the antimicrobial therapy alone is not effective. A novel strategy to prevent biofilm formation is based on the interference with the bacterial cell–cell communication, a process known as quorum sensing (QS) and mediated by the RNA-III-activating peptide (RAP) and its target protein TRAP (Target of RAP). The RNAIII inhibiting peptide (RIP) is able to inhibit S. aureus pathogenesis by disrupting QS mechanism competing with RAP, thus inhibiting the phosphorylation of TRAP. This alteration leads to a reduced adhesion and to the inhibition of RNAIII synthesis, with the subsequent suppression of toxins synthesis. The present paper will provide an overview on the activity and potential applications of RIP as biofilm inhibiting compound, useful in the management of S. aureus biofilm infections. Moreover, medicinal chemistry strategies have been examined to better understand which modifications and/or structure alterations were able to produce new derivatives of this QS inhibitor with an improved antibiofilm activity.


2019 ◽  
Author(s):  
Caitlin N. Esoda ◽  
Meta J. Kuehn

AbstractPseudomonas aeruginosa, known as one of the leading causes of morbidity and mortality in cystic fibrosis (CF) patients, secretes a variety of virulence-associated proteases. These enzymes have been shown to contribute significantly toP. aeruginosapathogenesis and biofilm formation in the chronic colonization of CF patient lungs, as well as playing a role in infections of the cornea, burn wounds and chronic wounds. Our lab has previously characterized a secretedP. aeruginosapeptidase, PaAP, that is highly expressed in chronic CF isolates. This leucine aminopeptidase is not only secreted solubly, it also associates with bacterial outer membrane vesicles (OMVs), structures known for their contribution to virulence mechanisms in a variety of Gram-negative species and one of the major components of the biofilm matrix. With this in mind, we hypothesized that PaAP may play a role inP. aeruginosabiofilm formation. Using a lung epithelial cell/bacterial biofilm coculture model, we show that PaAP deletion in a clinicalP. aeruginosabackground leads to increased early biofilm formation. We additionally found that only native vesicle-bound PaAP, as opposed to its soluble forms, could reconstitute the original PaAP-mediated inhibition phenotype, and that the PaAP-containing vesicles could disperse preformed biofilm microcolonies ofKlebsiella pneumoniae, another lung pathogen. These data provide the basis for future work into the mechanism behind PaAP-OMV mediated bacterial microcolony dispersal and the application of these findings to clinical anti-biofilm research.


2021 ◽  
Vol 9 (11) ◽  
pp. 2308
Author(s):  
Yusuke Iwabuchi ◽  
Tomoyo Nakamura ◽  
Yasuka Kusumoto ◽  
Ryoma Nakao ◽  
Tsutomu Iwamoto ◽  
...  

Streptococcus mutans releases membrane vesicles (MVs) and induces MV-dependent biofilm formation. Glucosyltransferases (Gtfs) are bound to MVs and contribute to the adhesion and glucans-dependent biofilm formation of early adherent bacteria on the tooth surface. The biofilm formation of S. mutans may be controlled depending on whether the initial pH tends to be acidic or alkaline. In this study, the characteristics and effects of MVs extracted from various conditions {(initial pH 6.0 and 8.0 media prepared with lactic acid (LA) and acetic acid (AA), and with NaOH (NO), respectively)} on the biofilm formation of S. mutans and early adherent bacteria were investigated. The quantitative changes in glucans between primary pH 6.0 and 8.0 conditions were observed, associated with different activities affecting MV-dependent biofilm formation. The decreased amount of Gtfs on MVs under the initial pH 6.0 conditions strongly guided low levels of MV-dependent biofilm formation. However, in the initial pH 6.0 and 8.0 solutions prepared with AA and NO, the MVs in the biofilm appeared to be formed by the expression of glucans and/or extracellular DNA. These results suggest that the environmental pH conditions established by acid and alkaline factors determine the differences in the local pathogenic activities of biofilm development in the oral cavity.


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