Biochemical investigation has shown that vitreous humor contains a variety of substances vital for bacterial growth.
32,33 However, antimicrobial agents such as lysozyme and cationic antimicrobial peptides (CAMPs), which are important components of the innate response, are also present in the vitreous body.
34 –36 It is possible that these antimicrobial agents in VH act more effectively against WTA-null mutants than against wild-type
S. aureus. However, others have reported that the antimicrobial activity of lysozyme, lactoferrin, and some CAMPs are not affected by the lack of WTAs.
12,28,37 Furthermore, the absence of WTAs in
S. aureus causes a selective increase in bacterial resistance to CAMPs, such as group IIA phospholipase A
2 and human β-defensin 3, potentially because WTAs, which are anionic polymers, may participate in the binding of CAMPs.
28 Other potential VH antimicrobial agents are proteases. A recent report demonstrated that some proteases could exhibit antimicrobial activity.
38 –40 In our study, a heat-stable, protease-K–sensitive component in VH was directly or indirectly responsible for VH killing activity. Serine protease inhibitors selectively rescued WTA-deficient mutants from the killing action of VH. Serine proteases contain an activated serine residue at the active site, and some serine proteases could have antimicrobial activity.
39,40 Although CAMPs function by disrupting anionic bacterial surfaces, the serine proteases may degrade bacterial proteins including virulence factors.
40 Since WTAs are located outside of the cell wall and are covalently linked to peptidoglycan, they could protect the cell wall or membrane from protease cleavage. We re-examined possible direct antimicrobial activity of common serine proteases that could contribute to VH antimicrobial activity for
S. aureus. Plasmin, thrombin, or neutrophil elastase did not show antimicrobial activity against either wild-type or WTA mutants (data not shown). Further investigation is needed to determine precisely what synergizes with the inhibitors of WTA in VH.