Superhydrophobic Nanocoatings as Intervention against Biofilm-Associated Bacterial Infections

Biofilm formation represents a significant cause of concern as it has been associated with increased morbidity and mortality, thereby imposing a huge burden on public healthcare system throughout the world. As biofilms are usually resistant to various conventional antimicrobial interventions, they may result in severe and persistent infections, which necessitates the development of novel therapeutic strategies to combat biofilm-based infections. Physicochemical modification of the biomaterials utilized in medical devices to mitigate initial microbial attachment has been proposed as a promising strategy in combating polymicrobial infections, as the adhesion of microorganisms is typically the first step for the formation of biofilms. For instance, superhydrophobic surfaces have been shown to possess substantial anti-biofilm properties attributed to the presence of nanostructures. In this article, we provide an insight into the mechanisms underlying biofilm formation and their composition, as well as the applications of nanomaterials as superhydrophobic nanocoatings for the development of novel anti-biofilm therapies.

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Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies

Frontiers in Microbiology ◽

10.3389/fmicb.2020.589726 ◽

2020 ◽

Vol 11 ◽

Author(s):

Lihui Chen ◽

Jie Li ◽

Wu Zhu ◽

Yehong Kuang ◽

Tao Liu ◽

...

Keyword(s):

Therapeutic Strategy ◽

Therapeutic Strategies ◽

Intestinal Microbiome ◽

Core Microbiome ◽

The Core ◽

The World ◽

Novel Therapeutic Strategies ◽

Insight Into ◽

Gaining Insight

Psoriasis affects the health of myriad populations around the world. The pathogenesis is multifactorial, and the exact driving factor remains unclear. This condition arises from the interaction between hyperproliferative keratinocytes and infiltrating immune cells, with poor prognosis and high recurrence. Better clinical treatments remain to be explored. There is much evidence that alterations in the skin and intestinal microbiome play an important role in the pathogenesis of psoriasis, and restoration of the microbiome is a promising preventive and therapeutic strategy for psoriasis. Herein, we have reviewed recent studies on the psoriasis-related microbiome in an attempt to confidently identify the “core” microbiome of psoriasis patients, understand the role of microbiome in the pathogenesis of psoriasis, and explore new therapeutic strategies for psoriasis through microbial intervention.

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Innovations in point of care testing for bacterial infections: The Longitude Prize with Daniel Berman

Video Journal of Biomedicine ◽

10.2217/vjbm-2020-0007 ◽

2020 ◽

Author(s):

Daniel Berman

Keyword(s):

Antimicrobial Resistance ◽

Diagnostic Tests ◽

Bacterial Infections ◽

Point Of Care ◽

Rapid Diagnostic Tests ◽

Public Healthcare ◽

Point Of Care Testing ◽

Set Up ◽

Insight Into

Antimicrobial resistance (AMR) is one of the most serious clinical and public healthcare challenges. In this video Daniel Berman, Nesta Challenges, provides an overview of the Longitude Prize, why the prize was set up and what the prize hopes to achieve. Daniel also provides insight into some of the rapid diagnostic tests currently in the running for the £8 million prize.

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Bacterial Biofilm Inhibition: A Focused Review on Recent Therapeutic Strategies for Combating the Biofilm Mediated Infections

Frontiers in Microbiology ◽

10.3389/fmicb.2021.676458 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ramanathan Srinivasan ◽

Sivasubramanian Santhakumari ◽

Pandurangan Poonguzhali ◽

Mani Geetha ◽

Madhu Dyavaiah ◽

...

Keyword(s):

Biofilm Formation ◽

Bacterial Infections ◽

Experimental Studies ◽

Therapeutic Strategies ◽

Bacterial Biofilm ◽

Control Measures ◽

Healthcare Sector ◽

Public Health Medicine ◽

Adhesive Properties ◽

Biofilm Inhibition

Biofilm formation is a major concern in various sectors and cause severe problems to public health, medicine, and industry. Bacterial biofilm formation is a major persistent threat, as it increases morbidity and mortality, thereby imposing heavy economic pressure on the healthcare sector. Bacterial biofilms also strengthen biofouling, affecting shipping functions, and the offshore industries in their natural environment. Besides, they accomplish harsh roles in the corrosion of pipelines in industries. At biofilm state, bacterial pathogens are significantly resistant to external attack like antibiotics, chemicals, disinfectants, etc. Within a cell, they are insensitive to drugs and host immune responses. The development of intact biofilms is very critical for the spreading and persistence of bacterial infections in the host. Further, bacteria form biofilms on every probable substratum, and their infections have been found in plants, livestock, and humans. The advent of novel strategies for treating and preventing biofilm formation has gained a great deal of attention. To prevent the development of resistant mutants, a feasible technique that may target adhesive properties without affecting the bacterial vitality is needed. This stimulated research is a rapidly growing field for applicable control measures to prevent biofilm formation. Therefore, this review discusses the current understanding of antibiotic resistance mechanisms in bacterial biofilm and intensely emphasized the novel therapeutic strategies for combating biofilm mediated infections. The forthcoming experimental studies will focus on these recent therapeutic strategies that may lead to the development of effective biofilm inhibitors than conventional treatments.

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A Critical, Nonlinear Threshold Dictates Bacterial Invasion and Initial Kinetics During Influenza

10.1101/052175 ◽

2016 ◽

Cited By ~ 1

Author(s):

Amber M. Smith ◽

Amanda P. Smith

Keyword(s):

Growth Rate ◽

Kinetic Model ◽

Influenza A Virus ◽

Influenza A ◽

Bacterial Infections ◽

Therapeutic Strategies ◽

Bacterial Invasion ◽

Dose Requirement ◽

Dose Threshold ◽

Insight Into

ABSTRACTSecondary bacterial infections increase morbidity and mortality of influenza A virus (IAV) infections. Bacteria are able to invade due to virus-induced depletion of alveolar macrophages (AMs), but this is not the only contributing factor. By analyzing a kinetic model, we uncovered a nonlinear initial dose threshold that is dependent on the amount of virus-induced AM depletion. The threshold separates the growth and clearance phenotypes such that bacteria decline for dose-AM depletion combinations below the threshold, stay constant near the threshold, and increase above the threshold. In addition, the distance from the threshold correlates to the growth rate. Because AM depletion changes throughout an IAV infection, the dose requirement for bacterial invasion also changes accordingly. Using the threshold, we found that the dose requirement drops dramatically during the first 7d of IAV infection. We then validated these analytical predictions by infecting mice with doses below or above the predicted threshold over the course of IAV infection. These results identify the nonlinear way in which two independent factors work together to support successful post-influenza bacterial invasion. They provide insight into coinfection timing, the heterogeneity in outcome, the probability of acquiring a coinfection, and the use of new therapeutic strategies to combat viral-bacterial coinfections.

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Crosstalk Between Staphylococcus aureus and Innate Immunity: Focus on Immunometabolism

Frontiers in Immunology ◽

10.3389/fimmu.2020.621750 ◽

2021 ◽

Vol 11 ◽

Author(s):

Christopher M. Horn ◽

Tammy Kielian

Keyword(s):

Staphylococcus Aureus ◽

Metabolic Pathways ◽

Biofilm Formation ◽

Bacterial Infections ◽

Current Knowledge ◽

Innate Immune ◽

Community Settings ◽

Leukocyte Activation ◽

Inflammatory Status ◽

Novel Therapeutic Strategies

Staphylococcus aureus is a leading cause of bacterial infections globally in both healthcare and community settings. The success of this bacterium is the product of an expansive repertoire of virulence factors in combination with acquired antibiotic resistance and propensity for biofilm formation. S. aureus leverages these factors to adapt to and subvert the host immune response. With the burgeoning field of immunometabolism, it has become clear that the metabolic program of leukocytes dictates their inflammatory status and overall effectiveness in clearing an infection. The metabolic flexibility of S. aureus offers an inherent means by which the pathogen could manipulate the infection milieu to promote its survival. The exact metabolic pathways that S. aureus influences in leukocytes are not entirely understood, and more work is needed to understand how S. aureus co-opts leukocyte metabolism to gain an advantage. In this review, we discuss the current knowledge concerning how metabolic biases dictate the pro- vs. anti-inflammatory attributes of various innate immune populations, how S. aureus metabolism influences leukocyte activation, and compare this with other bacterial pathogens. A better understanding of the metabolic crosstalk between S. aureus and leukocytes may unveil novel therapeutic strategies to combat these devastating infections.

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whISOBAXTM Inhibits Bacterial Pathogenesis and Enhances the Effect of Antibiotics

Antibiotics ◽

10.3390/antibiotics9050264 ◽

2020 ◽

Vol 9 (5) ◽

pp. 264 ◽

Cited By ~ 1

Author(s):

Reuven Rasooly ◽

Hwang-Yong Choi ◽

Paula Do ◽

Gianluca Morroni ◽

Lucia Brescini ◽

...

Keyword(s):

Gallic Acid ◽

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Bacterial Infections ◽

Phenolic Content ◽

Toxin Production ◽

Gram Negative Bacteria ◽

Persistent Infections ◽

Toxin Inhibition

As bacteria are becoming more resistant to commonly used antibiotics, alternative therapies are being sought. whISOBAX (WH) is a witch hazel extract that is highly stable (tested up to 2 months in 37 °C) and contains a high phenolic content, where 75% of it is hamamelitannin and traces of gallic acid. Phenolic compounds like gallic acid are known to inhibit bacterial growth, while hamamelitannin is known to inhibit staphylococcal pathogenesis (biofilm formation and toxin production). WH was tested in vitro for its antibacterial activity against clinically relevant Gram-positive and Gram-negative bacteria, and its synergy with antibiotics determined using checkerboard assays followed by isobologram analysis. WH was also tested for its ability to suppress staphylococcal pathogenesis, which is the cause of a myriad of resistant infections. Here we show that WH inhibits the growth of all bacteria tested, with variable efficacy levels. The most WH-sensitive bacteria tested were Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis, followed by Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Streptococcus agalactiae and Streptococcus pneumoniae. Furthermore, WH was shown on S. aureus to be synergistic to linezolid and chloramphenicol and cumulative to vancomycin and amikacin. The effect of WH was tested on staphylococcal pathogenesis and shown here to inhibit biofilm formation (tested on S. epidermidis) and toxin production (tested on S. aureus Enterotoxin A (SEA)). Toxin inhibition was also evident in the presence of subinhibitory concentrations of ciprofloxacin that induces pathogenesis. Put together, our study indicates that WH is very effective in inhibiting the growth of multiple types of bacteria, is synergistic to antibiotics, and is also effective against staphylococcal pathogenesis, often the cause of persistent infections. Our study thus suggests the benefits of using WH to combat various types of bacterial infections, especially those that involve resistant persistent bacterial pathogens.

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TFEB Biology and Agonists at a Glance

Cells ◽

10.3390/cells10020333 ◽

2021 ◽

Vol 10 (2) ◽

pp. 333

Author(s):

Mingyue Chen ◽

Yashuang Dai ◽

Siyu Liu ◽

Yuxin Fan ◽

Zongxian Ding ◽

...

Keyword(s):

Transcriptional Regulator ◽

Therapeutic Strategies ◽

Disease Models ◽

Cellular Survival ◽

Promising Strategy ◽

Pathogenic Factors ◽

Transcription Factor Eb ◽

Novel Therapeutic Strategies ◽

And Function ◽

Novel Therapeutic

Autophagy is a critical regulator of cellular survival, differentiation, development, and homeostasis, dysregulation of which is associated with diverse diseases including cancer and neurodegenerative diseases. Transcription factor EB (TFEB), a master transcriptional regulator of autophagy and lysosome, can enhance autophagic and lysosomal biogenesis and function. TFEB has attracted a lot of attention owing to its ability to induce the intracellular clearance of pathogenic factors in a variety of disease models, suggesting that novel therapeutic strategies could be based on the modulation of TFEB activity. Therefore, TFEB agonists are a promising strategy to ameliorate diseases implicated with autophagy dysfunction. Recently, several TFEB agonists have been identified and preclinical or clinical trials are applied. In this review, we present an overview of the latest research on TFEB biology and TFEB agonists.

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Loss of phenotypic inheritance associated with ydcI mutation leads to increased frequency of small, slow persisters in Escherichia coli

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1914741117 ◽

2020 ◽

Vol 117 (8) ◽

pp. 4152-4157 ◽

Cited By ~ 2

Author(s):

Suzanne M. Hingley-Wilson ◽

Nan Ma ◽

Yin Hu ◽

Rosalyn Casey ◽

Anders Bramming ◽

...

Keyword(s):

Escherichia Coli ◽

Transcription Factor ◽

Mutant Strain ◽

Phenotypic Variation ◽

Bacterial Infections ◽

Therapeutic Strategies ◽

Bacterial Cells ◽

Bacterial Persistence ◽

Insight Into ◽

Homogenous Population

Whenever a genetically homogenous population of bacterial cells is exposed to antibiotics, a tiny fraction of cells survives the treatment, the phenomenon known as bacterial persistence [G.L. Hobby et al., Exp. Biol. Med. 50, 281–285 (1942); J. Bigger, The Lancet 244, 497–500 (1944)]. Despite its biomedical relevance, the origin of the phenomenon is still unknown, and as a rare, phenotypically resistant subpopulation, persisters are notoriously hard to study and define. Using computerized tracking we show that persisters are small at birth and slowly replicating. We also determine that the high-persister mutant strain of Escherichia coli, HipQ, is associated with the phenotype of reduced phenotypic inheritance (RPI). We identify the gene responsible for RPI, ydcI, which encodes a transcription factor, and propose a mechanism whereby loss of phenotypic inheritance causes increased frequency of persisters. These results provide insight into the generation and maintenance of phenotypic variation and provide potential targets for the development of therapeutic strategies that tackle persistence in bacterial infections.

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Thiol and Disulfide Containing Vancomycin Derivatives Against Bacterial Resistance and Biofilm Formation

10.1101/2021.08.23.457343 ◽

2021 ◽

Author(s):

Inga S. Shchelik ◽

Karl Gademann

Keyword(s):

Biofilm Formation ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Resistant Bacteria ◽

Bacterial Strains ◽

Antibiotic Resistant ◽

Promising Strategy ◽

Vancomycin Resistant ◽

New Compounds ◽

Sulfur Containing

Antibiotic-resistant and biofilm-associated infections constitute a rapidly growing issue. The last resort antibiotic vancomycin is under threat, due to the increasing appearance of vancomycin resistant bacteria as well as the formation of biofilms. Herein, we report a series of novel vancomycin derivatives carrying thiol- and disulfide-containing moieties. The new compounds exhibited enhanced antibacterial activity against a broad range of bacterial strains, including vancomycin resistant microbes and Gram-negative bacteria. Moreover, all obtained derivatives demonstrated improved antibiofilm formation activity against VanB resistant Enterococcus compared to vancomycin. This work established a promising strategy for combating drug-resistant bacterial infections or disrupting biofilm formation and advances the knowledge on structural optimization of antibiotics with sulfur-containing modifications.

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Chemical Modulation of Mitochondria–Endoplasmic Reticulum Contact Sites

Cells ◽

10.3390/cells9071637 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1637 ◽

Cited By ~ 1

Author(s):

Ana Paula Magalhães Rebelo ◽

Federica Dal Bello ◽

Tomas Knedlik ◽

Natasha Kaar ◽

Fabio Volpin ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Therapeutic Strategies ◽

Comprehensive Overview ◽

Contact Sites ◽

Pharmacological Targets ◽

Close Proximity ◽

Original Insight ◽

Chemical Modulation ◽

Novel Therapeutic Strategies ◽

Insight Into

Contact sites between mitochondria and endoplasmic reticulum (ER) are points in which the two organelles are in close proximity. Due to their structural and functional complexity, their exploitation as pharmacological targets has never been considered so far. Notwithstanding, the number of compounds described to target proteins residing at these interfaces either directly or indirectly is rising. Here we provide original insight into mitochondria–ER contact sites (MERCs), with a comprehensive overview of the current MERCs pharmacology. Importantly, we discuss the considerable potential of MERCs to become a druggable target for the development of novel therapeutic strategies.

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