Role of cell-associated and secretion-independent virulence factors of Pseudomonas aeruginosa in microbial keratitis and anti-virulence therapeutic strategies

Microbial keratitis (MK) caused by Pseudomonas aeruginosa is a rapidly progressive and vision-threatening corneal infection worldwide. Even short delays in diagnosis or inappropriate therapy can lead to irreversible corneal scarring and blindness. This opportunistic pathogen colonizes, invades, and damages ocular tissue by taking advantage of disruptions in the corneal epithelial barrier and using a variety of virulence factors. The aim of this study was to summarize the current understanding of P. aeruginosa’s cell-associated, and secretion system-independent virulence factors involved in MK and investigate their potential as therapeutic targets. A literature search was performed using PubMed, Scopus, Web of Science, MEDLINE, and Google Scholar to review experimental and clinical studies on P. aeruginosa keratitis, with a focus on virulence factors, host-pathogen interactions, and emerging anti-virulence strategies. Search terms included combinations of P. aeruginosa, microbial keratitis, bacterial keratitis, corneal infection, corneal ulcer, virulence factors, surface- and cell-associated virulence factors, secretion-independent and contact-dependent virulence factors, pathogenicity, and anti-virulence therapies. Flagella, type IV pili, lipopolysaccharides, outer-membrane proteins, adhesins, biofilm matrix polysaccharides (Psl, Pel, alginate), siderophores, quorum-sensing networks, and secreted metabolites such as pyocyanin may be the key virulence factors in MK. These factors can influence host-pathogen interactions, corneal immunological homeostasis, and encourage drug tolerance and bacterial persistence. Moreover, targeting cell-associated and secretion system-independent virulence mechanisms represents a promising complementary approach along with conventional antimicrobial therapy. A deeper understanding of the virulence factors may enable the design of targeted therapies. Such approaches could mitigate corneal damage and vision loss while reducing selective pressure for antibiotic resistance.