A Novel Biomimetic Nanosponge Protects the Retina from the Enterococcus faecalis Cytolysin

LaGrow, Austin L.; Coburn, Phillip S.; Miller, Frederick C.; Land, Craig; Parkunan, Salai Madhumathi; Luk, Brian T.; Gao, Weiwei; Zhang, Liangfang; Callegan, Michelle C.

doi:10.1128/msphere.00335-17

Cited by 33 publications

(43 citation statements)

References 56 publications

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“…At the time of tissue harvest, mice were anesthetized and euthanized by cardiac perfusion with10 to 20 ml of PBS. After euthanasia, the numbers of P. aeruginosa CFU in eyes, HGs, and ELGs were quantified by track dilution on BHI agar, as described previously (48,49). Colonies were confirmed as Pseudomonas on Pseudomonas isolation agar (Sigma).…”

Section: Methodsmentioning

confidence: 99%

Ocular Glands Become Infected Secondarily to Infectious Keratitis and Play a Role in Corneal Resistance to Infection

Montgomery

Callegan

Fuller

et al. 2019

J Virol

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Ocular glands play a critical role in eye health through the secretion of factors directly onto the ocular surface. The cornea is a normally transparent tissue necessary for visual acuity located in the anterior segment of the eye. Corneal damage can occur during microbial infection of the cornea, resulting in potentially permanent visual deficits. The involvement of ocular glands during corneal infection has been only briefly described. We hypothesized that ocular glands contribute to resistance as an arm of the eye-associated lymphoid tissue and may also be susceptible to infection secondary to microbial keratitis. Utilizing a mouse model of herpes simplex virus 1 (HSV-1) keratitis, we found that infection of corneas resulted in subsequent infection of ocular glands, including harderian glands (HGs) and extraorbital glands. Similarly, infection of corneas with Pseudomonas aeruginosa resulted in secondary infection of ocular glands. A robust immune response, characterized by increased numbers of immune cells and inflammatory mediators, occurred within ocular glands following HSV-1 keratitis. Removal of HGs altered corneal resistance to HSV-1, as measured by increased viral load, decreased corneal edema, and decreased inflammatory cell infiltration. These novel findings suggest that ocular glands are involved in microbial keratitis through their susceptibility to secondary infection and contribution to corneal resistance. IMPORTANCE Microbial keratitis accounts for up to 700,000 clinical visits annually in the United States. The involvement of ocular glands during microbial keratitis is not readily appreciated, and treatment options do not address the consequences of ocular gland dysfunction. The present study shows that ocular glands are susceptible to direct infection by common ocular pathogens, including HSV-1 and Pseudomonas aeruginosa, subsequent to microbial keratitis. Additionally, ocular glands contribute soluble factors that play a role in corneal resistance to HSV-1 and alter viral load, corneal edema, and immune cell infiltration. Further studies are needed to elucidate the mechanisms by which this occurs.

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Section: Methodsmentioning

confidence: 99%

Ocular Glands Become Infected Secondarily to Infectious Keratitis and Play a Role in Corneal Resistance to Infection

Montgomery

Callegan

Fuller

et al. 2019

J Virol

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“…Every 2 hours, 20-μL aliquots were track diluted in PBS and plated onto BHI agar plates, and counted after 24 hours [2,6,21,23,26,65,[65][66][67]. Values are expressed in percent hemolysis relative to a 100% lysis control, as previously described [16,19,26,61,68].Values represent the means ± SD of two independent experiments.…”

Section: Bacterial Growth Curvesmentioning

confidence: 99%

“…PMN infiltration into eyes was estimated by quantifying MPO using a sandwich ELISA (Hycult Biotech, Plymouth Meeting, PA, USA) as previously described [6,27,65,66] [26,66,68]. P values of < 0.05 were considered significant.…”

Section: Estimation Of Inflammatory Cell Influxmentioning

confidence: 99%

Immune Inhibitor A Metalloproteases Contribute to Virulence inBacillusEndophthalmitis

Livingston

Mursalin

Coburn

et al. 2020

Preprint

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AbstractBacterial endophthalmitis is a devastating infection that can cause blindness following the introduction of organisms into the posterior segment of the eye. Over half of Bacillus endophthalmitis cases result in significant loss of useful vision. Often, these eyes have to be enucleated. Bacillus produces many virulence factors in the eye that may contribute to retinal damage and robust inflammation. This study analyzed Bacillus immune inhibitor A (InhA) metalloproteases, which digest extracellular matrix, tight junction proteins, and antimicrobial proteins. We hypothesized that InhAs contribute to Bacillus intraocular virulence and inflammation. We analyzed phenotypes and infectivity of wild type (WT), InhA1-deficient (ΔinhA1), InhA2-deficient (ΔinhA2), or InhA1, A2, and A3-deficient (ΔinhA1-3) Bacillus thuringiensis. In vitro analysis of growth, proteolysis, and cytotoxicity were compared between B. thuringiensis strains. WT and InhA mutants were similarly cytotoxic to retinal cells. Mutant ΔinhA1 and ΔinhA2 entered log phase growth earlier than WT. Proteolysis of the ΔinhA1-3 mutant was decreased, but this strain grew similar to WT in vitro. Experimental endophthalmitis was initiated by intravitreally infecting C57BL/6J mice with 200 CFU of B. thuringiensis WT or InhA mutants. Intraocular Bacillus and retinal function loss were quantified. Intraocular myeloperoxidase concentrations were quantified and histology was analyzed. Eyes infected with ΔinhA1 or ΔinhA2 strains contained greater numbers of bacteria than eyes infected with WT throughout the course of infection. Eyes infected with single mutants had inflammation and retinal function loss similar to eyes infected with WT strain. Eyes infected with ΔinhA1-3 cleared the infection, with less retinal function loss and inflammation compared to eyes infected with the WT strain. RT-PCR results suggested that single InhA mutant results may be explained by compensatory expression of the other InhAs in these mutants. These results indicate that together, the InhA metalloproteases contribute to the severity of infection and inflammation in Bacillus endophthalmitis.Author summaryBacterial endophthalmitis is an infection of the eye, which can follow accidental contamination of the posterior segment following ocular surgery (postoperative), a penetrating wound (post-traumatic), or during spread of bacteria into the eye from the bloodstream (endogenous). During bacterial endophthalmitis, virulent pathogens such as Bacillus cause ocular damage via the activities of an array of virulence factors, including proteases. A class of proteases that are expressed by Bacillus during ocular infection are the immune inhibitor A metalloproteases. Here, we used a mouse model of endophthalmitis to test mutant Bacillus that lack single or multiple InhAs to determine if these metalloproteases contributed to the virulence during the disease. In the absence of the production of all InhAs, Bacillus could not cause severe infection. Our study provides new insights into the virulence of Bacillus in the eye, and the contribution of its InhA metalloproteases to establishing infection.

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“…16 These NPs are fused with natural cell membranes and can absorb and neutralize molecules. 17,18 The neutrophil membranecoated NPs have been described to neutralize pro-inflammatory cytokines, suppress inflammation, and against joint damage. 19 Taken together, the membrane coated NPs containing miRNA could be an efficient treatment for MI.…”

Section: Introductionmentioning

confidence: 99%

Engineered macrophage membrane‐enveloped nanomedicine for ameliorating myocardial infarction in a mouse model

Xue¹,

Zeng²,

Jin³

et al. 2020

Bioengineering & Transla Med

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Myocardial infarction (MI) is the serious condition causing lots of death over the world. Myocytes apoptosis, inflammation, and fibrosis are three important factors implicated in pathogenesis of MI. Targeting these three factors has been shown to ameliorate MI and rescue cardiac function. Previous studies have demonstrated that microRNA (miR) 199a‐3p protect against MI. In this study, we prepare macrophage membrane coated nanoparticles (MMNPs) containing miR199a‐3p. We evaluate the effects of these NPs on apoptosis and cell proliferation in vitro and the effects on inflammation cytokine production, expression of fibrosis related proteins, cardiac injuries, and functions in MI mice. We find that the MMNPs have receptors of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor alpha (TNF‐α) and can bind to these cytokines. MMNPs prevent hypoxia‐induced apoptosis and promote cell proliferation, suppress the inflammation, and inhibit the cardiac fibrosis in MI mice. These results demonstrate that MMNPs ameliorate left ventricular remodeling and cardiac functions, and protect against MI, suggesting MMNPs containing miR199a‐3p is a potential therapeutic approach to treat MI.

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A Novel Biomimetic Nanosponge Protects the Retina from the Enterococcus faecalis Cytolysin

Cited by 33 publications

References 56 publications

Ocular Glands Become Infected Secondarily to Infectious Keratitis and Play a Role in Corneal Resistance to Infection

Ocular Glands Become Infected Secondarily to Infectious Keratitis and Play a Role in Corneal Resistance to Infection

Immune Inhibitor A Metalloproteases Contribute to Virulence inBacillusEndophthalmitis

Engineered macrophage membrane‐enveloped nanomedicine for ameliorating myocardial infarction in a mouse model

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