mazEF Homologue Has a Minor Role in Staphylococcus epidermidis 1457 Virulence Potential

Staphylococcus epidermidis biofilm cells are characterized by increased antimicrobial tolerance and improved ability to evade host immune system defenses. These features are, in part, due to the presence of viable but non-culturable (VBNC) cells. A previous study identified genes potentially involved in VBNC cells formation in S. epidermidis biofilms, among which SERP1682/1681 raised special interest due to their putative role as a toxin–antitoxin system of the mazEF family. Herein, we constructed an S. epidermidis mutant lacking the mazEF genes homologues and determined their role in (i) VBNC state induction during biofilm formation, (ii) antimicrobial susceptibility, (iii) survival in human blood and plasma, and (iv) activation of immune cells. Our results revealed that mazEF homologue did not affect the proportion of VBNC cells in S. epidermidis 1457, refuting the previous hypothesis that mazEF homologue could be linked with the emergence of VBNC cells in S. epidermidis biofilms. Additionally, mazEF homologue did not seem to influence key virulence factors on this strain, since its deletion did not significantly affect the mutant biofilm formation capacity, antimicrobial tolerance or the response by immune cells. Surprisingly, our data suggest that mazEF does not behave as a toxin–antitoxin system in S. epidermidis strain 1457, since no decrease in the viability and culturability of bacteria was found when only the mazF toxin homologue was being expressed.

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Regulation of Biofilm Formation by σB is a Common Mechanism in Staphylococcus Epidermidis and is not Mediated by Transcriptional Regulation of sarA

The International Journal of Artificial Organs ◽

10.1177/039139880903200907 ◽

2009 ◽

Vol 32 (9) ◽

pp. 584-591 ◽

Cited By ~ 11

Author(s):

Sebastian JÄger ◽

Beate Jonas ◽

Dorothea Pfanzelt ◽

Matthias A. Horstkotte ◽

Holger Rohde ◽

...

Keyword(s):

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Film Formation ◽

Transcriptional Analysis ◽

Common Mechanism ◽

Minor Role ◽

Regulatory Pathway ◽

Pathogenetic Factor ◽

A Minor ◽

The Impact

Biofilm formation is a major pathogenetic factor of Staphylococcus epidermidis. In S. epidermidis the alternative sigma factor σB was identified to regulate biofilm formation in S. epidermidis 1457. In S. aureus σB dependent regulation plays a minor role, whereas sarA (Staphylococcus accessory regulator) is an essential regulator. Therefore, we investigated the impact of σB on sarA transcription and biofilm formation in three independent S. epidermidis isolates. Mutants with dysfunctional σB displayed a strongly reduced biofilm formation, whereas in mutants with constitutive σB activity bio film formation was increased. Transcriptional analysis revealed that IcaA transcription was down-regulated in all σB negative mutants while icaR transcription was up-regulated. However, transcriptional differences varied between individual strains, indicating that additional σB-dependent regulators are involved in biofilm expression. Interestingly, despite the presence of a σB promoter beside two σA promoters no differences, or only minor ones, were observed in sarA transcription, indicating that σB-dependent sarA transcript has no influence on the phenotypic changes. The data observed in independent clinical S. epidermidis isolates suggests that, in contrast to S. aureus, regulation of biofilm formation by σB is a general feature in S. epidermidis. Additionally, we were able to demonstrate that the sarA- dependent regulation is not involved in this regulatory pathway.

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Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis

Nature Communications ◽

10.1038/s41467-021-21748-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Poushali Chakraborty ◽

Sapna Bajeli ◽

Deepak Kaushal ◽

Bishan Dass Radotra ◽

Ashwani Kumar

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune System ◽

Biofilm Formation ◽

Antimycobacterial Activity ◽

Drug Tolerance ◽

Host Immune System ◽

Tissue Sections ◽

Slow Growing

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.

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Emerging nanomedicines for effective breast cancer immunotherapy

Journal of Nanobiotechnology ◽

10.1186/s12951-020-00741-z ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Amirhossein Bahreyni ◽

Yasir Mohamud ◽

Honglin Luo

Keyword(s):

Breast Cancer ◽

Immune System ◽

Cancer Immunotherapy ◽

Immune Cells ◽

Tumor Antigens ◽

Host Immune System ◽

Primary Tumors ◽

Novel Approach ◽

Tumor Environment ◽

Advanced Biomaterials

AbstractBreast cancer continues to be the most frequently diagnosed malignancy among women, putting their life in jeopardy. Cancer immunotherapy is a novel approach with the ability to boost the host immune system to recognize and eradicate cancer cells with high selectivity. As a promising treatment, immunotherapy can not only eliminate the primary tumors, but also be proven to be effective in impeding metastasis and recurrence. However, the clinical application of cancer immunotherapy has faced some limitations including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells as well as uncontrolled modulation of immune system, which can give rise to autoimmunity and nonspecific inflammation. Growing evidence has suggested that nanotechnology may meet the needs of current cancer immunotherapy. Advanced biomaterials such as nanoparticles afford a unique opportunity to maximize the efficiency of immunotherapy and significantly diminish their toxic side-effects. Here we discuss recent advancements that have been made in nanoparticle-involving breast cancer immunotherapy, varying from direct activation of immune systems through the delivery of tumor antigens and adjuvants to immune cells to altering immunosuppression of tumor environment and combination with other conventional therapies.

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Enhancement of immune response against Bordetella spp. by disrupting immunomodulation

Scientific Reports ◽

10.1038/s41598-019-56652-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Monica C. Gestal ◽

Laura K. Howard ◽

Kalyan Dewan ◽

Hannah M. Johnson ◽

Mariette Barbier ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Cells ◽

Lymphoid Tissue ◽

Protective Immunity ◽

Inflammatory Cells ◽

Host Immune System ◽

Initial Growth ◽

Wild Type ◽

Sterilizing Immunity

AbstractWell-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the respiratory tract of mice, its natural host, but did increase activation of the inflammasome pathway, and recruitment of inflammatory cells. The mutant lacking btrS recruited many more B and T cells into the lungs, where they rapidly formed highly organized and distinctive Bronchial Associated Lymphoid Tissue (BALT) not induced by any wild type Bordetella species, and a much more rapid and strong antibody response than observed with any of these species. Immunity induced by the mutant was measurably more robust in all respiratory organs, providing completely sterilizing immunity that protected against challenge infections for many months. Moreover, the mutant induced sterilizing immunity against infection with other classical bordetellae, including B. pertussis and B. parapertussis, something the current vaccines do not provide. These findings reveal profound immunomodulation by bordetellae and demonstrate that by disrupting it much more robust protective immunity can be generated, providing a pathway to greatly improve vaccines and preventive treatments against these important pathogens.

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Leishmanial selenoproteins and the host immune system: towards new therapeutic strategies?

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/traa013 ◽

2020 ◽

Vol 114 (7) ◽

pp. 541-544

Author(s):

Sajad Rashidi ◽

Kurosh Kalantar ◽

Paul Nguewa ◽

Gholamreza Hatam

Keyword(s):

Immune System ◽

Adverse Effects ◽

Immune Responses ◽

Immune Cells ◽

Therapeutic Strategies ◽

Host Immune System ◽

Host Immune Responses ◽

Leishmania Parasites

Abstract Optimum levels of selenoproteins are essential for starting and managing the host immune responses against pathogens. According to the expression of selenoproteins in Leishmania parasites, and since high levels of selenoproteins lead to adverse effects on immune cells and their functions, Leishmania parasites might then express selenoproteins such as selenomethionine in their structure and/or secretions able to challenge the host immune system. Finally, this adaptation may lead to evasion of the parasite from the host immune system. The expression of selenoproteins in Leishmania parasites might then induce the development of infection. We therefore suggest these molecules as new therapeutic candidates for the treatment of leishmaniasis.

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Biofilm Formation Avoids Complement Immunity and Phagocytosis of Streptococcus pneumoniae

Infection and Immunity ◽

10.1128/iai.00491-13 ◽

2013 ◽

Vol 81 (7) ◽

pp. 2606-2615 ◽

Cited By ~ 81

Author(s):

Mirian Domenech ◽

Elisa Ramos-Sevillano ◽

Ernesto García ◽

Miriam Moscoso ◽

Jose Yuste

Keyword(s):

Immune System ◽

Streptococcus Pneumoniae ◽

Biofilm Formation ◽

Complement Component ◽

Factor H ◽

Human Neutrophils ◽

Host Immune System ◽

Complement Pathway ◽

Content Type ◽

Alternative Complement

ABSTRACTStreptococcus pneumoniaeis a frequent member of the microbiota of the human nasopharynx. Colonization of the nasopharyngeal tract is a first and necessary step in the infectious process and often involves the formation of sessile microbial communities by this human pathogen. The ability to grow and persist as biofilms is an advantage for many microorganisms, because biofilm-grown bacteria show reduced susceptibility to antimicrobial agents and hinder recognition by the immune system. The extent of host protection against biofilm-related pneumococcal disease has not been determined yet. Using pneumococcal strains growing as planktonic cultures or as biofilms, we have investigated the recognition ofS. pneumoniaeby the complement system and its interactions with human neutrophils. Deposition of C3b, the key complement component, was impaired onS. pneumoniaebiofilms. In addition, binding of C-reactive protein and the complement component C1q to the pneumococcal surface was reduced in biofilm bacteria, demonstrating that pneumococcal biofilms avoid the activation of the classical complement pathway. In addition, recruitment of factor H, the downregulator of the alternative pathway, was enhanced byS. pneumoniaegrowing as biofilms. Our results also show that biofilm formation diverts the alternative complement pathway activation by a PspC-mediated mechanism. Furthermore, phagocytosis of pneumococcal biofilms was also impaired. The present study confirms that biofilm formation inS. pneumoniaeis an efficient means of evading both the classical and the PspC-dependent alternative complement pathways the host immune system.

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Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model

Frontiers in Microbiology ◽

10.3389/fmicb.2021.603151 ◽

2021 ◽

Vol 12 ◽

Author(s):

Manoj Kumar ◽

Madhvi Rao ◽

Tarun Mathur ◽

Tarani Kanta Barman ◽

Vattan Joshi ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Immune System ◽

Solid Surface ◽

Biofilm Formation ◽

Lung Infection ◽

Bacterial Attachment ◽

Placebo Control ◽

Infection Model ◽

Host Immune System

Pseudomonas aeruginosa forms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected with P. aeruginosa and improved their lung function. The present study was conducted to evaluate the effect of azithromycin on P. aeruginosa biofilm. We show that azithromycin exhibited a potent activity against P. aeruginosa biofilm, and microscopic observation revealed that azithromycin substantially inhibited the formation of solid surface biofilms. Interestingly, we observed that azithromycin restricted P. aeruginosa biofilm formation by inhibiting the expression of pel genes, which has been previously shown to play an essential role in bacterial attachment to solid-surface biofilm. In a rat model of chronic P. aeruginosa lung infection, we show that azithromycin treatment resulted in the suppression of quorum sensing-regulated virulence factors, significantly improving the clearance of P. aeruginosa biofilms compared to that in the placebo control. We conclude that azithromycin attenuates P. aeruginosa biofilm formation, impairs its ability to produce extracellular biofilm matrix, and increases its sensitivity to the immune system, which may explain the clinical efficacy of azithromycin in cystic fibrosis patients.

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Fis overexpression enhances Pseudomonas putida biofilm formation by regulating the ratio of LapA and LapF

Microbiology ◽

10.1099/mic.0.082503-0 ◽

2014 ◽

Vol 160 (12) ◽

pp. 2681-2693 ◽

Cited By ~ 14

Author(s):

Hanna Moor ◽

Annika Teppo ◽

Andrio Lahesaare ◽

Maia Kivisaar ◽

Riho Teras

Keyword(s):

Pseudomonas Putida ◽

Biofilm Formation ◽

Minor Role ◽

Wild Type ◽

Environmental Signals ◽

Sds Page ◽

Transposon Mutants ◽

Transcription Regulators ◽

Adhesive Proteins ◽

A Minor

Bacteria form biofilm as a response to a number of environmental signals that are mediated by global transcription regulators and alarmones. Here we report the involvement of the global transcription regulator Fis in Pseudomonas putida biofilm formation through regulation of lapA and lapF genes. The major component of P. putida biofilm is proteinaceous and two large adhesive proteins, LapA and LapF, are known to play a key role in its formation. We have previously shown that Fis overexpression enhances P. putida biofilm formation. In this study, we used mini-Tn5 transposon mutagenesis to select potential Fis-regulated genes involved in biofilm formation. A total of 90 % of the studied transposon mutants carried insertions in the lap genes. Since our experiments showed that Fis-enhanced biofilm is mostly proteinaceous, the amounts of LapA and LapF from P. putida cells lysates were quantified using SDS-PAGE. Fis overexpression increases the quantity of LapA 1.6 times and decreases the amount of LapF at least 4 times compared to the wild-type cells. The increased LapA expression caused by Fis overexpression was confirmed by FACS analysis measuring the amount of LapA-GFP fusion protein. Our results suggest that the profusion of LapA in the Fis-overexpressed cells causes enhanced biofilm formation in mature stages of P. putida biofilm and LapF has a minor role in P. putida biofilm formation.

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CandidaBiofilms and the Host: Models and New Concepts for Eradication

International Journal of Microbiology ◽

10.1155/2012/845352 ◽

2012 ◽

Vol 2012 ◽

pp. 1-16 ◽

Cited By ~ 44

Author(s):

Hélène Tournu ◽

Patrick Van Dijck

Keyword(s):

Immune System ◽

High Throughput ◽

Biofilm Formation ◽

Host Immune System ◽

Alternative Strategies ◽

New Concepts ◽

Potential Applications ◽

Lock Therapy

Biofilms define mono- or multispecies communities embedded in a self-produced protective matrix, which is strongly attached to surfaces. They often are considered a general threat not only in industry but also in medicine. They constitute a permanent source of contamination, and they can disturb the proper usage of the material onto which they develop. This paper relates to some of the most recent approaches that have been elaborated to eradicateCandidabiofilms, based on the vast effort put in ever-improving models of biofilm formationin vitroandin vivo, including novel flow systems, high-throughput techniques and mucosal models. Mixed biofilms, sustaining antagonist or beneficial cooperation between species, and their interplay with the host immune system are also prevalent topics. Alternative strategies against biofilms include the lock therapy and immunotherapy approaches, and material coating and improvements. The host-biofilm interactions are also discussed, together with their potential applications inCandidabiofilm elimination.

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Impact of Gold Nanoparticles on the Functions of Macrophages and Dendritic Cells

Cells ◽

10.3390/cells10010096 ◽

2021 ◽

Vol 10 (1) ◽

pp. 96

Author(s):

Arindam K. Dey ◽

Alexis Gonon ◽

Eve-Isabelle Pécheur ◽

Mylène Pezet ◽

Christian Villiers ◽

...

Keyword(s):

Gold Nanoparticles ◽

Dendritic Cells ◽

Immune System ◽

Immune Cells ◽

Biomedical Applications ◽

Minor Effect ◽

Tnf Α ◽

A Minor ◽

Antigen Presenting ◽

Inflammatory Molecules

Gold nanoparticles (AuNPs) have demonstrated outstanding performance in many biomedical applications. Their safety is recognised; however, their effects on the immune system remain ill defined. Antigen-presenting cells (APCs) are immune cells specialised in sensing external stimulus and in capturing exogenous materials then delivering signals for the immune responses. We used primary macrophages (Ms) and dendritic cells (DCs) of mice as an APC model. Whereas AuNPs did not alter significantly Ms and DCs functions, the exposure to AuNPs affected differently Ms and DCs in their responses to subsequent stimulations. The secretion of inflammatory molecules like cytokines (IL-6, TNF-α), chemokine (MCP-1), and reactive oxygen species (ROS) were altered differently in Ms and DCs. Furthermore, the metabolic activity of Ms was affected with the increase of mitochondrial respiration and glycolysis, while only a minor effect was seen on DCs. Antigen presentation to T cells increased when DCs were exposed to AuNPs leading to stronger Th1, Th2, and Th17 responses. In conclusion, our data provide new insights into the complexity of the effects of AuNPs on the immune system. Although AuNPs may be considered as devoid of significant effect, they may induce discrete modifications on some functions that can differ among the immune cells.

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