Development and stability of bacteriocin resistance in Campylobacter spp.

Abstract

Aims Several bacteriocins (BCNs) that were identified from chicken commensal bacteria dramatically reduced Campylobacter colonization in poultry and are being directed toward on-farm control of this important foodborne human pathogen. A recent study has shown that BCN resistance in C. jejuni is very difficult to develop in vitro. In this study, in vivo development and stability of BCN resistance in Campylobacter was examined. Methods and Results Chickens infected with C. jejuni NCTC 11168 were treated with BCN E-760 at the dose of 5 mg/kg body weight/day via oral gavages for three consecutive days, which selected BCN-resistant (BCNr) mutants in the treated birds. However, all the in vivo-selected mutants only displayed low-levels of resistance to BCN (MIC = 2–8 mg/L) when compared to parent strain (MIC = 0.5 mg/L). Inactivation of CmeABC efflux pump of the BCNr mutants led to increased susceptibility to BCN (8–32 fold MIC reduction). Three different BCNr Campylobacter strains (in vitro- or in vivo-derived) were examined for the stability of BCN resistance using both in vitro and in vivo systems. The low-level of BCN resistance in these strains was not stable in vitro or in vivo in the absence of BCN selection pressure. Conclusions Usage of BCN E-760 only selected low-level BCNr C. jejuni mutants in vivo and the low-level BCN resistance was not stable in vitro and in vivo. Significance and Impact of the Study The study provides helpful information for risk assessment of the future practical application of the anti-Campylobacter BCNs in animals.

Global Epidemiology of Campylobacter Infection

“…For example, in a study by Svetoch and Stern, treatment of chickens with the bacteriocin L-1077, produced by Lactobacillus salivarius strain L-1077 isolated from broiler chickens, resulted in decreases in cecal C. jejuni counts of Ͼ4 log compared with those for untreated control birds (408). In addition, the effects of three other bacteriocins, OR-7 from Lactobacillus salivarius and E-760 and E50-52 from Enterococcus faecium, have been investigated (409). Administration of these three bacteriocins to chickens resulted in dramatic reductions of 5 to 8 log 10 CFU in C. jejuni intestinal colonization (409).…”

Characterization of bacterial antimicrobial peptides active against Campylobacter jejuni

“…As with bacteriocin OR-7, efflux pump CmeABC was implicated in a resistance mechanism of C. jejuni to E-760. 7,8 Inactivation of CmeABC increased the susceptibility of the resistant strains to E-760 from 8-to 32-fold. 7 The amino acid sequence of enterocin E-760 consists of 62 amino acids, as determined through Edman degradation (Fig.…”

“…75 The propensity for C. jejuni to develop resistance to enterocin E-760 was recently studied. 7 Following the administration of E-760 to chickens, C. jejuni isolates only showed the development of low levels of resistance. Furthermore, this resistance was unstable, with a tendency to be lost in the absence of the selective pressure exerted by the bacteriocin.…”

“…The development of resistance to antimicrobial peptides tends to be less prevalent than to antibiotics, and the resistance mechanisms that develop may be unstable or have an associated fitness cost. 7,8 Still, resistance to clinically promising antimicrobial peptides such as daptomycin (approved by the US FDA in 2003) 9 may be quick to develop. 10 Bacteriocins (i.e., ribosomally synthesized antimicrobial peptides produced by bacteria) tend to be more selective than antibiotics, potentially avoiding complications associated with disrupting the bacterial microflora (e.g., Clostridium difficile associated diarrhea).…”

Inactivation of the LysR regulator Cj1000 of Campylobacter jejuni affects host colonization and respiration

“…cj0999c has been described as a putative sapZ homologue (Hoang, 2010). sap genes are involved in antimicrobial peptide defences in Haemophilus influenzae (Shelton et al, 2011), and a recent publication demonstrated their role in C. jejuni defences against fowlicidin-1, a major antimicrobial peptide of the chicken immune system (Hoang et al, 2011;Hoang, 2010).…”