and P Infectious Keratitis: Key Bacterial Mechanisms That Mediate Pathogenesis and Emerging Therapeutics

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2023 Sep 6

PMID 37671149

Authors

Shalini Shah

Rachel A F Wozniak

Affiliations

Soon will be listed here.

Abstract

Bacterial keratitis (bacterial infection of the cornea) is a major cause of vision loss worldwide. Given the rapid and aggressive nature of the disease, immediate broad-spectrum antibiotics are essential to adequately treat this disease. However, rising antibiotic resistance continues to accelerate, rendering many commonly used therapeutics increasingly ineffective. As such, there is a significant effort to understand the basic pathogenesis of common causative organisms implicated in keratitis in part, to fuel the development of novel therapies to treat this blinding disease. This review explores two common causes of bacterial keratitis, and , with regards to the bacterial mediators of virulence as well as novel therapies on the horizon.

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References

Papaioannou L, Miligkos M, Papathanassiou M . Corneal Collagen Cross-Linking for Infectious Keratitis: A Systematic Review and Meta-Analysis. Cornea. 2015; 35(1):62-71. DOI: 10.1097/ICO.0000000000000644. View

Tang A, Marquart M, Fratkin J, McCormick C, Caballero A, Gatlin H . Properties of PASP: a Pseudomonas protease capable of mediating corneal erosions. Invest Ophthalmol Vis Sci. 2009; 50(8):3794-801. PMC: 2874894. DOI: 10.1167/iovs.08-3107. View

Malloy J, Veldhuizen R, Thibodeaux B, OCallaghan R, Wright J . Pseudomonas aeruginosa protease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functions. Am J Physiol Lung Cell Mol Physiol. 2004; 288(2):L409-18. DOI: 10.1152/ajplung.00322.2004. View

Tang A, Caballero A, Marquart M, OCallaghan R . Pseudomonas aeruginosa small protease (PASP), a keratitis virulence factor. Invest Ophthalmol Vis Sci. 2013; 54(4):2821-8. PMC: 3632270. DOI: 10.1167/iovs.13-11788. View

Keay L, Edwards K, Naduvilath T, Taylor H, Snibson G, Forde K . Microbial keratitis predisposing factors and morbidity. Ophthalmology. 2005; 113(1):109-16. DOI: 10.1016/j.ophtha.2005.08.013. View

Thibodeaux B, Caballero A, Dajcs J, Marquart M, Engel L, OCallaghan R . Pseudomonas aeruginosa protease IV: a corneal virulence factor of low immunogenicity. Ocul Immunol Inflamm. 2005; 13(2-3):169-82. DOI: 10.1080/09273940490518937. View

Mei J, Johnson W, Kinn B, Laskey E, Nolin L, Bhamare P . Antimicrobial Activity of a Triple Antibiotic Combination Toward Ocular Pseudomonas aeruginosa Clinical Isolates. Transl Vis Sci Technol. 2022; 11(5):26. PMC: 9145016. DOI: 10.1167/tvst.11.5.26. View

Hsiao C, Kang E, Yeh L, Ma D, Chen H, Hung K . Keratitis in Taiwan: Genotyping, Antibiotic Susceptibility, and Clinical Features. Int J Mol Sci. 2022; 23(19). PMC: 9570272. DOI: 10.3390/ijms231911703. View

Ting D, Ho C, Cairns J, Elsahn A, Al-Aqaba M, Boswell T . 12-year analysis of incidence, microbiological profiles and in vitro antimicrobial susceptibility of infectious keratitis: the Nottingham Infectious Keratitis Study. Br J Ophthalmol. 2020; 105(3):328-333. PMC: 7907586. DOI: 10.1136/bjophthalmol-2020-316128. View

10.

Bialasiewicz A, Shenoy R, Thakral A, Al-Muniri A, Shenoy U, Al-Mughairi Z . [Microbial keratitis: a 4 year study of risk factors and traditional/complementary medicine in Oman]. Ophthalmologe. 2006; 103(8):682-7. DOI: 10.1007/s00347-006-1363-2. View

11.

Karthikeyan R, Lakshmi Priya J, Leal Jr S, Toska J, Rietsch A, Prajna V . Host response and bacterial virulence factor expression in Pseudomonas aeruginosa and Streptococcus pneumoniae corneal ulcers. PLoS One. 2013; 8(6):e64867. PMC: 3672173. DOI: 10.1371/journal.pone.0064867. View

12.

Barac I, Artamonov A, Balta G, Dinu V, Mehedintu C, Bobirca A . Photoactivated Chromophore Corneal Collagen Cross-Linking for Infectious Keratitis (PACK-CXL)-A Comprehensive Review of Diagnostic and Prognostic Factors Involved in Therapeutic Indications and Contraindications. J Pers Med. 2022; 12(11). PMC: 9698237. DOI: 10.3390/jpm12111907. View

13.

Engel L, Hill J, Caballero A, Green L, OCallaghan R . Protease IV, a unique extracellular protease and virulence factor from Pseudomonas aeruginosa. J Biol Chem. 1998; 273(27):16792-7. DOI: 10.1074/jbc.273.27.16792. View

14.

Lomholt J, Poulsen K, Kilian M . Epidemic population structure of Pseudomonas aeruginosa: evidence for a clone that is pathogenic to the eye and that has a distinct combination of virulence factors. Infect Immun. 2001; 69(10):6284-95. PMC: 98763. DOI: 10.1128/IAI.69.10.6284-6295.2001. View

15.

Bourcier T, Thomas F, Borderie V, Chaumeil C, Laroche L . Bacterial keratitis: predisposing factors, clinical and microbiological review of 300 cases. Br J Ophthalmol. 2003; 87(7):834-8. PMC: 1771775. DOI: 10.1136/bjo.87.7.834. View

16.

Thomas R, Melton R, Vollmer P, Asbell P . In Vitro Antibiotic Resistance among Bacteria from the Cornea in the Antibiotic Resistance Monitoring in Ocular MicRoorganisms Surveillance Study. Optom Vis Sci. 2021; 98(9):1113-1121. PMC: 8505161. DOI: 10.1097/OPX.0000000000001768. View

17.

White C, Alionte L, Cannon B, Caballero A, OCallaghan R, Hobden J . Corneal virulence of LasA protease--deficient Pseudomonas aeruginosa PAO1. Cornea. 2001; 20(6):643-6. DOI: 10.1097/00003226-200108000-00017. View

18.

Hebert W, DiGiandomenico A, Zegans M . Multifunctional Monoclonal Antibody Targeting Keratitis in Mice. Vaccines (Basel). 2020; 8(4). PMC: 7712430. DOI: 10.3390/vaccines8040638. View

19.

Ung L, Bispo P, Shanbhag S, Gilmore M, Chodosh J . The persistent dilemma of microbial keratitis: Global burden, diagnosis, and antimicrobial resistance. Surv Ophthalmol. 2018; 64(3):255-271. PMC: 7021355. DOI: 10.1016/j.survophthal.2018.12.003. View

20.

Laskey E, Chen Y, Sohn M, Gruber E, Chojnacki M, Wozniak R . Efficacy of a Novel Ophthalmic Antimicrobial Drug Combination Toward a Large Panel of Staphylococcus aureus Clinical Ocular Isolates From Around the World. Cornea. 2020; 39(10):1278-1284. PMC: 7483989. DOI: 10.1097/ICO.0000000000002414. View