Evaluation of the potential of colicins to prevent extraluminal contamination of urinary catheters by Escherichia coli.

The feasibility of using colicins to create an antimicrobial lubricant to prevent extraluminal catheter contamination during urinary catheter insertion was assessed. Levels of resistance of uropathogenic Escherichia coli to antibiotics and colicins were compared. The results showed that antibiotics and colicins possess similar frequencies of resistance to a single drug, whereas colicins exhibit significantly lower levels of multidrug resistance (22%) than antibiotics (42%). Colicins and antibiotics showed complementary inhibitory activity, with each targeting different subsets of pathogenic isolates. The collateral impact of these two antimicrobials on genera that are members of the fecal/vaginal/urinary microbiome was assessed, with colicins showing significantly less collateral damage than antibiotics. Using a novel colicin, SR4, minimum inhibitory concentrations (MICs) for a panel of 30 uropathogenic isolates were determined and showed that SR4 achieved the same antimicrobial efficacy as gentamicin using 20-30% less drug. An SR4-impregnated catheter lubricant was created and its ability to prevent extraluminal urinary catheter contamination in vitro was demonstrated. These data indicate that a colicin-impregnated lubricant may provide a viable prophylactic option for preventing catheter-associated urinary tract infections.

Pheromonicins: an ecologically sound family of bacteriocin-based antibiotics for use in the age of the microbiome.

The time is ripe to usher in a new paradigm in infection control and to move beyond our sole reliance on broad-spectrum antibiotics whose use results in extensive collateral damage to our microbiome and, in so doing, exerts significant selective pressures for resistance to emerge. We propose to supplement the existing pharmacy of conventional antibiotics, with a new drug family, the pheromonicins. These bacteriocin-based antimicrobials are stable, nontoxic proteins that possess potent antibacterial activities, and which can be easily and rapidly retargeted against any bacteria desired. Here we discuss colicin Ia, a pore forming bacteriocin, as the base of a novel drug development platform, the pheromonicins. Recent work suggests this versatile drug development platform can be used to generate pheromonicins active against enveloped viruses, fungi and human cancer cells. Pheromonicins provide a less toxic, more ecologically sound alternative to conventional antibiotics, and their use will help limit our sole reliance on broad-spectrum drugs.