Abstract
Therapeutic solutions to counter Burkholderia cepacia complex (Bcc) bacteria are challenging due to their intrinsically high level of antibiotic resistance. Bcc organisms display a variety of potential virulence factors, have a distinct lipopolysaccharide naturally implicated in antimicrobial resistance. and are able to form biofilms, which may further protect them from both host defence peptides (HDPs) and antibiotics. Here, we report the promising anti-biofilm and immunomodulatory activities of human HDP GVF27 on two of the most clinically relevant Bcc members, Burkholderia multivorans and Burkholderia cenocepacia. The effects of synthetic and labelled GVF27 were tested on B. cenocepacia and B. multivorans biofilms, at three different stages of formation, by confocal laser scanning microscopy (CLSM). Assays on bacterial cultures and on human monocytes challenged with B. cenocepacia LPS were also performed. GVF27 exerts, at different stages of formation, anti-biofilm effects towards both Bcc strains, a significant propensity to function in combination with ciprofloxacin, a relevant affinity for LPSs isolated from B. cenocepacia as well as a good propensity to mitigate the release of pro-inflammatory cytokines in human cells pre-treated with the same endotoxin. Overall, all these findings contribute to the elucidation of the main features that a good therapeutic agent directed against these extremely leathery biofilm-forming bacteria should possess.
Highlights
Multi-drug resistance in bacteria is one of the most pressing global health issues of our time [1,2]
This paper focuses on a panel of bioactivities of GVF27 directed against two extremely virulent members of Burkholderia cepacia complex (Bcc), such as B. cenocepacia and B. multivorans
GVF27 (5 μM for B. multivorans and 5-10-20 μM for B. cenocepacia) are enough to affect the growth of planktonic cells; even more interesting is the evidence that the same concentrations are effective in inhibiting biofilm adhesion and formation
Summary
Multi-drug resistance in bacteria is one of the most pressing global health issues of our time [1,2]. HDPs attenuate immune response through several types of actions, as binding to endotoxins, contribution to the enhancement of innate immune processes by promoting chemotaxis of neutrophils, monocytes, eosinophils, dendritic cells, and T-lymphocytes to the site of infection, stimulation of chemokine production, and modulation of wound healing/re-epithelialisation of injured infected tissues [7–11]. This wide range of properties attribute to HDPs a critical role in mammalian innate immunity and makes them very attractive as an effective alternative to conventional antibiotics for developing new anti-infective agents [12,13]. This group of Gram negative closely-related species phylogenetically but not phenotypically distinguishable, known as genomovars, cover a prominent role in determining serious health risks with drastically limited treatment options in immunocompromised individuals [14,15]
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