Clearance of Gram-Negative Bacterial Pathogens from the Ocular Surface by Predatory Bacteria

Eric G Romanowski,Daniel E Kadouri,Robert M Q Shanks,Androulla Pericleous,Shilpi Gupta

doi:10.3390/antibiotics10070810

Eric G Romanowski, Daniel E Kadouri + Show 3 more

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https://doi.org/10.3390/antibiotics10070810

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Abstract

It was previously demonstrated that predatory bacteria are able to efficiently eliminate Gram-negative pathogens including antibiotic-resistant and biofilm-associated bacteria. In this proof-of-concept study we evaluated whether two species of predatory bacteria, Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus, were able to alter the survival of Gram-negative pathogens on the ocular surface. Clinical keratitis isolates of Pseudomonas aeruginosa (strain PAC) and Serratia marcescens (strain K904) were applied to the ocular surface of NZW rabbits followed by application of predatory bacteria. At time intervals, surviving pathogenic bacteria were enumerated. In addition, B. bacteriovorus and S. marcescens were applied to porcine organ culture corneas under contact lenses, and the ocular surface was examined by scanning electron microscopy. The ocular surface epithelial layer of porcine corneas exposed to S. marcescens, but not B. bacteriovorus was damaged. Using this model, neither pathogen could survive on the rabbit ocular surface for longer than 24 h. M. aeruginosavorus correlated with a more rapid clearance of P. aeruginosa but not S. marcescens from rabbit eyes. This study supports previous evidence that predatory bacteria are well tolerated by the cornea, but suggest that predatory bacteria do not considerably change the ability of the ocular surface to clear the tested Gram-negative bacterial pathogens from the ocular surface.

Highlights

Predatory bacteria including Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are Gram-negative bacteria that prey upon other Gram-negative bacteria [1,2]
Antibiotic we evaluated the ability of B. bacteriovorus and M. aeruginosavorus to promote the clearance resistance has been noted among keratitis isolates and is correlated with worse clinical of keratitis isolates of S. marcescens and fluoroquinolone-resistant P. aeruginosa and from the outcomes [24,25,26,27,28,29]
Vivo cornea in order to determine whether predatory bacteria could adhere to the corneal surface a first step in the study visualized of predatory and andAs whether there was anywe clear impactthe of interaction this interaction usingbacteria

Summary

Introduction

Predatory bacteria including Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are Gram-negative bacteria that prey upon other Gram-negative bacteria [1,2]. B. bacteriovorus has a broad host-range by which it invades the bacterial cell and replicates in the bacterial periplasm, whereas M. aeruginosavorus exhibits a narrower host-range and acts as an epibiotic predator as it attaches to the outside of prey bacteria [5]. These predators were shown to be highly effective against bacteria in biofilms, which are notoriously recalcitrant to traditional antibiotic therapy [6,7,8,9]. Intravenous and intranasal inoculation of Micavibrio and Bdellovibrio species, even at high numbers, caused no morbidity or mortality in mice, they did mildly increase production of proinflammatory cytokines IL-6, TNFalpha, and chemokine CXCL-1 [13], and numerous mammalian cell lines were unperturbed

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