Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis

Abstract

Background Bloodstream infections with antibiotic-resistant Pseudomonas aeruginosa are common and increasingly difficult to treat. Pyocins are naturally occurring protein antibiotics produced by P. aeruginosa that have potential for human use. Objectives To determine if pyocin treatment is effective in a murine model of sepsis with P. aeruginosa. Methods Recombinant pyocins S5 and AP41 were purified and tested for efficacy in a Galleria mellonella infection model and a murine model of P. aeruginosa sepsis. Results Both pyocins produced no adverse effects when injected alone into mice and showed good in vitro antipseudomonal activity. In an invertebrate model of sepsis using G. mellonella, both pyocins significantly prolonged survival from 1/10 (10%) survival in controls to 80%–100% survival among groups of 10 pyocin-treated larvae. Following injection into mice, both showed extensive distribution into different organs. When administered 5 h after infection, pyocin S5 significantly increased survival from 33% (2/6) to 83% (5/6) in a murine model of sepsis (difference significant by log-rank test, P < 0.05). Conclusions Pyocins S5 and AP41 show in vivo biological activity and can improve survival in two models of P. aeruginosa infection. They hold promise as novel antimicrobial agents for treatment of MDR infections with this microbe.

Bacterial pore-forming toxins

“…A recent study showed that colicins can be used to disrupt biofilm integrity [223]. Moreover, when injected into the bloodstream of mice, pyocin S5 was observed to retain its functionality and to improve mouse survival to Pseudomonas infections [224]. Another study demonstrated that microcapsule delivery of the active form of colicin Ia reduced E. coli colonisation in murine models [225].…”

«Study of 32 new phage tail-like bacteriocins (pyocins) from a clinical collection of Pseudomonas aeruginosa and of their potential use as typing markers and antimicrobial agents»

“…When the 32 clinical isolates were tested against the 32 isolated pyocins, none were able to lyse the source strain or those strains with the same serotype or ST. As previously described, variability in the susceptibility to the pyocins was observed between those isolates that shared ST and/or serotype and the same type of pyocin, probably due to the frequently observed mutations in the LPS genes in CF, affecting recognition by the RBP 7,26,27 . Pyocins have been considered potential alternatives to antibiotics, and several studies have demonstrated antimicrobial activity of pyocins alone or in combination with other antimicrobials and those sharing the LPS as target 9,19,20,28,29 .…”

“…The R-type pyocins were used for the rst time in 1969 to rescue chick embryos infected with P. aeruginosa 17 . In addition, several assays in murine models con rmed the e cacy of R-type pyocins in the treatment of infections with P. aeruginosa 9,18,19 . Due to the narrow spectrum of the PTLBs, some studies focused on generating recombinant R-type pyocins to retarget them by substituting the tail ber protein with a phage protein in order to increase the host range in several species such as P. aeruginosa, Clostridioides di cile and Listeria monocytogenes 8,20−23 .…”

A Shaving Proteomic Approach to Unveil Surface Proteins Modulation of Multi-Drug Resistant Pseudomonas aeruginosa Strains Isolated From Cystic Fibrosis Patients

“…In the competition for the ecological niche, bacteria develop multiple mechanisms to ensure their survival and predominance. PA produces siderophores, such as pyoverdine, pyochelin and pyocianin (i.e., PyoS5), to bind iron and to transport it from the extracellular region into the bacterium through the outer membrane receptor FptA, a TonB-dependent transporter (70)(71)(72)(73)(74)(75)(76).…”