An Eye to a Kill: Using Predatory Bacteria to Control Gram-Negative Pathogens Associated with Ocular Infections

Abstract

Ocular infections are a leading cause of vision loss. It has been previously suggested that predatory prokaryotes might be used as live antibiotics to control infections. In this study, Pseudomonas aeruginosa and Serratia marcescens ocular isolates were exposed to the predatory bacteria Micavibrio aeruginosavorus and Bdellovibrio bacteriovorus. All tested S. marcescens isolates were susceptible to predation by B. bacteriovorus strains 109J and HD100. Seven of the 10 P. aeruginosa isolates were susceptible to predation by B. bacteriovorus 109J with 80% being attacked by M. aeruginosavorus. All of the 19 tested isolates were found to be sensitive to at least one predator. To further investigate the effect of the predators on eukaryotic cells, human corneal-limbal epithelial (HCLE) cells were exposed to high concentrations of the predators. Cytotoxicity assays demonstrated that predatory bacteria do not damage ocular surface cells in vitro whereas the P. aeruginosa used as a positive control was highly toxic. Furthermore, no increase in the production of the proinflammatory cytokines IL-8 and TNF-alpha was measured in HCLE cells after exposure to the predators. Finally, injection of high concentration of predatory bacteria into the hemocoel of Galleria mellonella, an established model system used to study microbial pathogenesis, did not result in any measurable negative effect to the host. Our results suggest that predatory bacteria could be considered in the near future as a safe topical bio-control agent to treat ocular infections.

Predation Efficacy of <i>Bdellovibrio bacteriovorus</i> on Multidrug-Resistant Clinical Pathogens and Their Corresponding Biofilms

“…The most efficient predation was found for E. coli in the MDR group, with a 3.11 log10 reduction in viability. The prey cells were not completely eradicated, but similar findings have been widely reported (7,21). It was noteworthy that the predator maintained its ability to prey on the clinical strains regardless of MDR or XDR status (Fig.…”

Purification and Host Specificity of Predatory Halobacteriovorax Isolates from Seawater

“…Other uses involve the treatment of various infections in animals, including bovine keratoconjunctivitis caused by Moraxella bovis (5), Aeromonas hydrophila in fish (6,7), Vibrio cholerae and Proteus penneri in shrimp (8,9), and Salmonella enterica serovar Enteritidis in the chicken gut (10). They have also been applied in the treatment of human disease pathogens, including Pseudomonas aeruginosa from the lungs of cystic fibrosis patients (11), Pseudomonas aeruginosa and Serratia marcescens associated with eye infections (12), and oral pathogens that cause periodontal diseases (13,14). Bdellovibrio strains were also effective in the treatment of drug-resistant bacteria (15,16) and in reducing the levels of Escherichia coli and Salmonella spp.…”

Predatory Prokaryotes Wage War Against Eye Infections

“…This bacterium has an extraordinary life cycle in which it collides with its prey, burrows through the bacterial membrane, divides into several daughter cells, and lyses the host bacteria to start a new round of predation [3]. Other predatory bacteria, such as Micavibrio aeruginosavorus may also have medical potential [4–6]; however, B. bacteriovorus will be discussed here as it is the most thoroughly studied.…”

“…Ocular surface infections such as bacterial conjunctivitis and microbial keratitis have a large cost to society and are a major source of vision loss. These infections are often caused by Gram-negative bacteria such as Haemophilus infuenzae , P. aeruginosa , and Serratia marcescens ; the latter two have been verified as being susceptible to predation by B. bacteriovorus [6]. …”