Beta-lactam-fosfomycin antagonism involving modification of penicillin-binding protein 3 in Pseudomonas aeruginosa

Abstract

Antagonism between fosfomycin and antipseudomonal penicillins, cefotaxime, and ceftriaxone was observed in Pseudomonas aeruginosa RYC212. Fosfomycin, a non-i-lactam antibiotic that acts on bacterial cell wall synthesis, decreased the expression of penicillin-binding protein 3 and induced j8-lactamase. The antagonistic effect was reduced in the presence of high concentrations of the ,l-lactamase inhibitor tazobactam or in fosfomycin-resistant mutants. We suggest that products resulting from fosfomycin cell wail damage could interact with a system that regulates penicillin-binding protein and I8-lactamase production.

Fosfomycin enhances the expression of penicillin-binding protein 2 in methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains

“…In contrast with previous papers [18,19] which concluded in favour of a decrease of some PBPs in the presence of fosfomycin, our results showed that this antibiotic can also lead to the opposite effect. However, PBP3 was not perceptibly affected, in agreement with Utsui et al [18].…”

“…However, PBP3 was not perceptibly affected, in agreement with Utsui et al [18]. Moreover the results of Reguera et al [19] showed an obvious increase in the labelling of the PBPlb of Pseudomonas aemginosa, following growth in the presence of 4 /~g/ml (i.e. 1/8 × the MIC) fosfomycin; this change was not discussed by the authors.…”

Penicillin-binding proteins and bacterial resistance to beta-lactams

“…aeruginosa is also correlatable with that of E. coli (115), and binding of ,3-lactam antibiotics generally results in morphological changes similar to those observed in E. coli (29). Interestingly, fosfomycin decreases PBP 3 expression and antagonizes P-lactams, although the latter effect may be secondary to 3-lactamase induction (131). Non-p-lactamase-mediated resistance to P-lactams in clinical isolates and laboratory mutants has been reported and is associated with reduction in PBP 3 binding (57, 58).…”

Starvation‐independent sporulation in Myxococcus xanthus involves the pathway for β‐lactamase induction and provides a mechanism for competitive cell survival

“…Induction of ␤-lactamase and sporulation by agents that damage peptidoglycan D-cycloserine, phosphomycin, and vancomycin, which disrupt normal peptidoglycan biosynthesis, also induced ␤-lactamase and sporulation in M. xanthus. It had previously been shown that phosphomycin could induce ␤-lactamase in P. aeruginosa (Reguera et al, 1990).…”