Effect of antimicrobial peptides on colistin-susceptible and colistin-resistant strains of Klebsiella pneumoniae and Enterobacter asburiae

Abstract

In this study susceptibility to different antimicrobial peptides was investigated on colistin-susceptible and colistin-resistant identical pulsotype strains of KPC-2 producing Klebsiella pneumoniae ST258 as well as colistin-susceptible and colistin-resistant Enterobacter asburiae strains isolated from clinical samples. In our test, bacteria were exposed to 50 mg/ml lactoferrin, lysozyme and protamine - cationic antimicrobial peptides belonging to innate immune system and having structural similarity to polymyxins - in separate reactions. After 18 hours incubation of colonies were counted. 40% of colistin-resistant K. pneumoniae strains and 97% of colistin-susceptible counterpart strains were lysed by protamine whereas 87% and 100% colony forming unit decrease by lysozyme was seen, respectively. In the case of colistin-resistant E. asburiae strains 1 log10 cell count increase were observed after treatment with lysozyme and 1.56 log10 after lactoferrin exposure compared to the initial number whereas the colistin-susceptible showed no relevant cell count increase. Our findings suggest that acquired colistin-resistance in Enterobacteriaceae is associated with tolerance against antimicrobial peptides.

Colistin resistance associated with outer membrane protein change in Klebsiella pneumoniae and Enterobacter asburiae

“…The reports of OmpA and OmpX contributing to antimicrobial peptide resistance and outer membrane structural changes in Enterobacteriaceae and underproduction of OmpC leading to serum resistance in Enterobacter spp. concur with our previous observation of colistin-resistant E. asburiae and K. pneumoniae strains being tolerant to antimicrobial peptides [34].…”

Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions

“…Notably, in the report by Dobias et al (2017) the effects of LL-37 were assessed at a lower range than the one used in this study (<20 μg/ml or <4.5 μM). However, Kadar et al (2015) reported cross-resistance in Kpn between colistin and other antibacterial compounds, including lactoferrin, lysozyme, and protamine. Additionally Llobet et al (2009) reported cross resistance with human α-defensin 1 (HNP-1).…”

“…Colistin and the antimicrobial peptide LL-37 share similar bacteria-binding mechanisms, leading to the unresolved hypothesis that cross-resistance between colistin and LL-37 exists. Some studies have supported the cross-resistance hypothesis (Llobet et al, 2009; Napier et al, 2013; Kadar et al, 2015), whereas others have shown contrasting results (Moffatt et al, 2013) or no correlation (Garcia-Quintanilla et al, 2014; Dobias et al, 2017). In addition, altered virulence of Kpn as a result of colistin-resistance is also a matter of debate and some studies showed unaltered virulence by mgrB -insertions (Cannatelli et al, 2015; Arena et al, 2016), whereas another study reported increased virulence (Kidd et al, 2017).…”

Rescuing humanity by antimicrobial peptides against colistin-resistant bacteria

“…In another study, the effect of three AMPs including protamine, lysozyme, and lactoferrin on colistin-resistant K. pneumoniae and Enterobacter asburiae showed that lactoferrin did not any killing function but protamine and lysozyme exposition caused a 40% and 87% reduction of CFU on colistin-resistant K. pneumoniae isolate, respectively. All three AMPs had no effect on colistin-resistant E. asburiae and high-level tolerance was observed against these three AMPs (Kádár et al 2015 ). Hashemi et al evaluated the susceptibility of colistin-resistant clinical isolates of K. pneumoniae to a series of AMPs containing LL-37, cecropin A, magainin 1, CSA-13, CSA-44, CSA-131, CSA-138, and CSA-142.…”