Current Evidence for Corynebacterium on the Ocular Surface

Corynebacterium species are commonly found in the conjunctiva of healthy adults and are recognized as non-pathogenic bacteria. In recent years, however, Corynebacterium species have been reported to be potentially pathogenic in various tissues. We investigated Corynebacterium species on the ocular surface and reviewed various species of Corynebacterium in terms of their antimicrobial susceptibility and the underlying molecular resistance mechanisms. We identified a risk for Corynebacterium-related ocular infections in patients with poor immunity, such as patients with diabetes or long-term users of topical steroids, and in those with corneal epithelial damage due to trauma, contact lens wear, lagophthalmos, and trichiasis. The predominant strain in the conjunctiva was C. macginleyi, and the species associated with keratitis and conjunctivitis were C. macginleyi, C. propinquum, C. mastitidis, C. pseudodiphtheriticum, C. accolens, C. striatum, C. xerosis, and C. bovis. Overall, Corynebacterium species present on the ocular surface were resistant to quinolones, whereas those in the nasal cavity were more susceptible. The prevalence of fluoroquinolone-resistant Corynebacterium has not changed in the past 10 years; however, Corynebacterium species remain susceptible to third-generation cephems. In conclusion, the use of third-generation cephems should be a reasonable and pragmatic approach for treatment of ocular infections caused by Corynebacterium species.

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Current Evidence on the Ocular Surface Microbiota and Related Diseases

Microorganisms ◽

10.3390/microorganisms8071033 ◽

2020 ◽

Vol 8 (7) ◽

pp. 1033 ◽

Cited By ~ 3

Author(s):

Francesco Petrillo ◽

Danilo Pignataro ◽

Maria Annunziata Lavano ◽

Biagio Santella ◽

Veronica Folliero ◽

...

Keyword(s):

Ocular Surface ◽

Pathogenic Bacteria ◽

Potential Role ◽

The Body ◽

Current Evidence ◽

Oral Microbiota ◽

Culture Techniques ◽

Microbiome Composition ◽

Ophthalmic Diseases ◽

Pro Inflammatory Cytokines

The ocular surface microbiota refers to the resident non-pathogenic microorganisms that colonize conjunctiva and cornea. Several studies have shown that ocular surface epithelial cells can respond selectively to specific components of ocular pathogenic bacteria by producing pro-inflammatory cytokines and, in contrast, they do not respond to non-pathogenic bacteria, thus supporting the colonization by a real microbiota. However, the analysis of the ocular microbiome composition is essential for understanding the pathophysiology of various ophthalmic diseases. In this scenario, the first studies, which used microbiological culture techniques, reported a less diverse profile of the ocular microbiota compared with that recently discovered using new molecular-based methods. Indeed, until a few years ago, the microbiota of the ocular surface appeared to be dominated by Gram-positive and a few Gram-negative bacteria, as well as some fungal strains. In contrast, genomics has nowadays detected a remarkable diversity in the ocular surface microorganisms. Furthermore, recent studies suggest that the microbiota of other areas of the body, such as the gut and oral microbiota, are involved in the pathophysiology of several ophthalmic diseases. The aim of the present study is to highlight the current evidence on the ocular surface microbiota to better understand it and to investigate its potential role in the development of ophthalmic diseases.

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Antibiotics Application Strategies to Control Biofilm Formation in Pathogenic Bacteria

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666191112155905 ◽

2020 ◽

Vol 21 (4) ◽

pp. 270-286 ◽

Cited By ~ 2

Author(s):

Fazlurrahman Khan ◽

Dung T.N. Pham ◽

Sandra F. Oloketuyi ◽

Young-Mog Kim

Keyword(s):

Biofilm Formation ◽

Pathogenic Bacteria ◽

Extracellular Polymeric Substances ◽

Quorum Quenching ◽

Resistance Mechanisms ◽

Bacterial Biofilm ◽

Bacterial Cells ◽

High Concentration ◽

Biofilm Inhibition ◽

Abiotic Surfaces

Background: The establishment of a biofilm by most pathogenic bacteria has been known as one of the resistance mechanisms against antibiotics. A biofilm is a structural component where the bacterial community adheres to the biotic or abiotic surfaces by the help of Extracellular Polymeric Substances (EPS) produced by bacterial cells. The biofilm matrix possesses the ability to resist several adverse environmental factors, including the effect of antibiotics. Therefore, the resistance of bacterial biofilm-forming cells could be increased up to 1000 times than the planktonic cells, hence requiring a significantly high concentration of antibiotics for treatment. Methods: Up to the present, several methodologies employing antibiotics as an anti-biofilm, antivirulence or quorum quenching agent have been developed for biofilm inhibition and eradication of a pre-formed mature biofilm. Results: Among the anti-biofilm strategies being tested, the sub-minimal inhibitory concentration of several antibiotics either alone or in combination has been shown to inhibit biofilm formation and down-regulate the production of virulence factors. The combinatorial strategies include (1) combination of multiple antibiotics, (2) combination of antibiotics with non-antibiotic agents and (3) loading of antibiotics onto a carrier. Conclusion: The present review paper describes the role of several antibiotics as biofilm inhibitors and also the alternative strategies adopted for applications in eradicating and inhibiting the formation of biofilm by pathogenic bacteria.

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Antimicrobial properties of actively purified secondary metabolites isolated from different marine organisms

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200730144536 ◽

2020 ◽

Vol 21 ◽

Author(s):

Nilushi Indika Bamunu Arachchige ◽

Fazlurrahman Khan ◽

Young-Mog Kim

Keyword(s):

Secondary Metabolites ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Bacterial Species ◽

Antimicrobial Properties ◽

Antimicrobial Effect ◽

Cost Effective ◽

Resistance Mechanisms ◽

Marine Organisms ◽

Antimicrobial Compounds

Background: The treatment of infection caused by pathogenic bacteria becomes one of the serious concerns globally. The failure in the treatment was found due to the exhibition of multiple resistance mechanisms against the antimicrobial agents. Emergence of resistant bacterial species has also been observed due to prolong treatment using conventional antibiotics. To combat these problems, several alternative strategies have been employed using biological and chemically synthesized compounds as antibacterial agents. Marine organisms considered as one of the potential sources for the isolation of bioactive compounds due to the easily available, cost-effective, and eco-friendly. Methods: The online search methodology was adapted for the collection of information related to the antimicrobial properties of marine-derived compounds. These compound has been isolated and purified by different purification techniques, and their structure also characterized. Furthermore, the antibacterial activities have been reported by using broth microdilution as well as disc diffusion assays. Results: The present review paper describes the antimicrobial effect of diverse secondary metabolites which are isolated and purified from the different marine organisms. The structural elucidation of each secondary metabolite has also been done in the present paper, which will help for the in silico designing of the novel and potent antimicrobial compounds. Conclusion: A thorough literature search has been made and summarizes the list of antimicrobial compounds that are isolated from both prokaryotic and eukaryotic marine organisms. The information obtained from the present paper will be helpful for the application of marine compounds as antimicrobial agents against different antibiotic-resistant human pathogenic bacteria.

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Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Pharmaceutics ◽

10.3390/pharmaceutics13060905 ◽

2021 ◽

Vol 13 (6) ◽

pp. 905

Author(s):

Sangeeta Kumari ◽

Madhuri Dandamudi ◽

Sweta Rani ◽

Elke Behaeghel ◽

Gautam Behl ◽

...

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Pilot Scale ◽

Dry Eye Disease ◽

Rapid Screening ◽

Eye Disease ◽

Topical Steroids ◽

Nanostructured Lipid Carrier ◽

The Impact ◽

Ophthalmic Formulation

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.

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Structural and functional insights into esterase-mediated macrolide resistance

Nature Communications ◽

10.1038/s41467-021-22016-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Michał Zieliński ◽

Jaeok Park ◽

Barry Sleno ◽

Albert M. Berghuis

Keyword(s):

Active Site ◽

Pathogenic Bacteria ◽

Catalytic Mechanism ◽

Three Dimensional ◽

Resistance Mechanisms ◽

Docking Studies ◽

Macrolide Resistance ◽

Flexible Docking ◽

Sequence Identity ◽

Substrate Spectrum

AbstractMacrolides are a class of antibiotics widely used in both medicine and agriculture. Unsurprisingly, as a consequence of their exensive usage a plethora of resistance mechanisms have been encountered in pathogenic bacteria. One of these resistance mechanisms entails the enzymatic cleavage of the macrolides’ macrolactone ring by erythromycin esterases (Eres). The most frequently identified Ere enzyme is EreA, which confers resistance to the majority of clinically used macrolides. Despite the role Eres play in macrolide resistance, research into this family enzymes has been sparse. Here, we report the first three-dimensional structures of an erythromycin esterase, EreC. EreC is an extremely close homologue of EreA, displaying more than 90% sequence identity. Two structures of this enzyme, in conjunction with in silico flexible docking studies and previously reported mutagenesis data allowed for the proposal of a detailed catalytic mechanism for the Ere family of enzymes, labeling them as metal-independent hydrolases. Also presented are substrate spectrum assays for different members of the Ere family. The results from these assays together with an examination of residue conservation for the macrolide binding site in Eres, suggests two distinct active site archetypes within the Ere enzyme family.

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Sorting out the Superbugs: Potential of Sortase A Inhibitors among Other Antimicrobial Strategies to Tackle the Problem of Antibiotic Resistance

Antibiotics ◽

10.3390/antibiotics10020164 ◽

2021 ◽

Vol 10 (2) ◽

pp. 164 ◽

Cited By ~ 1

Author(s):

Nikita Zrelovs ◽

Viktorija Kurbatska ◽

Zhanna Rudevica ◽

Ainars Leonchiks ◽

Davids Fridmanis

Keyword(s):

Cell Wall ◽

Antibiotic Resistance ◽

Pathogenic Bacteria ◽

Resistance Mechanisms ◽

Surface Proteins ◽

Sortase A ◽

Inhibitory Compounds ◽

Alternative Means ◽

Alternative Approaches ◽

Conventional Antibiotics

Rapid spread of antibiotic resistance throughout the kingdom bacteria is inevitably bringing humanity towards the “post-antibiotic” era. The emergence of so-called “superbugs”—pathogen strains that develop resistance to multiple conventional antibiotics—is urging researchers around the globe to work on the development or perfecting of alternative means of tackling the pathogenic bacteria infections. Although various conceptually different approaches are being considered, each comes with its advantages and drawbacks. While drug-resistant pathogens are undoubtedly represented by both Gram(+) and Gram(−) bacteria, possible target spectrum across the proposed alternative approaches of tackling them is variable. Numerous anti-virulence strategies aimed at reducing the pathogenicity of target bacteria rather than eliminating them are being considered among such alternative approaches. Sortase A (SrtA) is a membrane-associated cysteine protease that catalyzes a cell wall sorting reaction by which surface proteins, including virulence factors, are anchored to the bacterial cell wall of Gram(+) bacteria. Although SrtA inhibition seems perspective among the Gram-positive pathogen-targeted antivirulence strategies, it still remains less popular than other alternatives. A decrease in virulence due to inactivation of SrtA activity has been extensively studied in Staphylococcus aureus, but it has also been demonstrated in other Gram(+) species. In this manuscript, results of past studies on the discovery of novel SrtA inhibitory compounds and evaluation of their potency were summarized and commented on. Here, we discussed the rationale behind the inhibition of SrtA, raised some concerns on the comparability of the results from different studies, and touched upon the possible resistance mechanisms as a response to implementation of such therapy in practice. The goal of this article is to encourage further studies of SrtA inhibitory compounds.

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Antibacterial Compounds from Mushrooms: A Lead to Fight ESKAPEE Pathogenic Bacteria?

Planta Medica ◽

10.1055/a-1266-6980 ◽

2020 ◽

Author(s):

Violette Hamers ◽

Clément Huguet ◽

Mélanie Bourjot ◽

Aurélie Urbain

Keyword(s):

Antibiotic Resistance ◽

Global Health ◽

Pathogenic Bacteria ◽

Resistance Mechanisms ◽

Pathogenic Microorganisms ◽

Bacterial Strains ◽

Antibacterial Compounds ◽

New Antibiotics ◽

Hospital Stays ◽

Antibacterial Potential

AbstractInfectious diseases are among the greatest threats to global health in the 21st century, and one critical concern is due to antibiotic resistance developed by an increasing number of bacterial strains. New resistance mechanisms are emerging with many infections becoming more and more difficult if not impossible to treat. This growing phenomenon not only is associated with increased mortality but also with longer hospital stays and higher medical costs. For these reasons, there is an urgent need to find new antibiotics targeting pathogenic microorganisms such as ESKAPEE bacteria. Most of currently approved antibiotics are derived from microorganisms, but higher fungi could constitute an alternative and remarkable reservoir of anti-infectious compounds. For instance, pleuromutilins constitute the first class of antibiotics derived from mushrooms. However, macromycetes still represent a largely unexplored source. Publications reporting the antibacterial potential of mushroom extracts are emerging, but few purified compounds have been evaluated for their bioactivity on pathogenic bacterial strains. Therefore, the aim of this review is to compile up-to-date data about natural products isolated from fruiting body fungi, which significantly inhibit the growth of ESKAPEE pathogenic bacteria. When available, data regarding modes of action and cytotoxicity, mandatory when considering a possible drug development, have been discussed in order to highlight the most promising compounds.

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The Relationship between Frequently Used Glucose-Lowering Agents and Gut Microbiota in Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2018/1890978 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

You Lv ◽

Xue Zhao ◽

Weiying Guo ◽

Ying Gao ◽

Shuo Yang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Short Chain Fatty Acids ◽

Current Evidence ◽

Diabetic Patients ◽

Glucose Lowering ◽

Patients With Diabetes ◽

Gastrointestinal Side Effects ◽

Underlying Mechanisms

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.

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Treatment in EGFR-mutated Non-small Cell Lung Cancer: How to Block the Receptor and overcome Resistance Mechanisms

Tumori Journal ◽

10.5301/tj.5000663 ◽

2017 ◽

Vol 103 (4) ◽

pp. 325-337 ◽

Cited By ~ 5

Author(s):

Claudia Proto ◽

Giuseppe Lo Russo ◽

Giulia Corrao ◽

Monica Ganzinelli ◽

Francesco Facchinetti ◽

...

Keyword(s):

Lung Cancer ◽

Growth Factor Receptor ◽

Resistance Mechanisms ◽

Small Cell ◽

Third Generation ◽

Small Cell Lung ◽

Epidermal Growth ◽

Exon 20 ◽

Egfr Mutated ◽

Egfr Tkis

In non-small cell lung cancer (NSCLC), the identification of epidermal growth factor receptor (EGFR) mutations and the parallel development of EGFR tyrosine kinase inhibitors (TKIs) have radically changed the therapeutic management strategies. Currently, erlotinib, gefitinib, and afatinib are all approved as standard first-line treatment in EGFR-mutated NSCLC. However, despite the proven efficacy, some EGFR-mutated NSCLCs do not respond to EGFR TKIs, while some patients, after a favorable and prolonged response to EGFR TKIs, inevitably progress within about 10-14 months. Epidermal growth factor receptor-dependent mechanisms, activation of alternative pathways, or phenotypic transformation can cause the resistance to EGFR TKIs. The exon 20 p.Thr790Met point mutation (T790M) is responsible for about 60% of cases of resistance when progression occurs. A third-generation TKI, osimertinib, improved outcome in patients harboring T790M after first- and second-generation TKI treatment. However, resistance develops even after treatment with third-generation drugs. To date, the Cys797Ser (C797S) mutation in exon 20 of EGFR is the most well-known resistance mutation after osimertinib. Fourth-generation TKIs are already under development. Nevertheless, additional information is needed to better understand and effectively overcome resistance. The aim of this review is to report recent advances and future perspectives in the treatment of EGFR-mutated NSCLC, highlighting the resistance mechanisms that underlie disease progression.

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