Research Article: Vertebrate odorant binding proteins as antimicrobial humoral components of innate immunity for pathogenic microorganisms

Date Published: March 22, 2019

Publisher: Public Library of Science

Author(s): Federica Bianchi, Sara Flisi, Maria Careri, Nicolò Riboni, Silvia Resimini, Andrea Sala, Virna Conti, Monica Mattarozzi, Simone Taddei, Costanza Spadini, Giuseppina Basini, Stefano Grolli, Clotilde Silvia Cabassi, Roberto Ramoni, Xin Deng.


The bacterium Pseudomonas aeruginosa (PA) and the yeast Candida albicans (CA) are pathogens that cohabit the mucosa of the respiratory tracts of animals and humans. Their virulence is largely determined by chemical communication driven by quorum sensing systems (QS), and the cross perception of their quorum sensing molecules (QSM) can modulate the prevalence of one microorganism over the other. Aiming to investigate whether some of the protein components dissolved in the mucus layering the respiratory mucosa might interfere with virulence and cross-communication of these, and eventually other microorganisms, ligand binding assays were carried out to test the scavenging potential of the bovine and porcine forms of the Lipocalin odorant binding protein (OBP) for several QSMs (farnesol, and acylhomoserine lactones), and for pyocyanin, a toxin produced by PA. In addition, the direct antimicrobial activity of the OBPs was tested by time kill assay (TKA) against CA, PA and other bacteria and yeasts. The positivity of all the ligand binding assays and the antimicrobial activity determined for CA, and for some of the other microorganisms tested, let hypothesize that vertebrate OBPs might behave as humoral components of innate immunity, active against pathogenic bacteria and fungi. In addition, TKAs with mutants of bovine OBP with structural properties different from those of the native form, and with OBP forms tagged with histidines at the amino terminal, provided information about the mechanisms responsible of their antimicrobial activity and suggested possible applications of the OBPs as alternative or co-adjuvants to antibiotic therapeutic treatments.

Partial Text

The Gram-negative bacterium Pseudomonas aeruginosa (PA) and the yeast Candida albicans (CA), which are commonly found in mixed infections in numerous animal species and in humans, are examples of pathogenic microorganisms that can be fatal in both immunocompromised patients and in subjects affected by cystic fibrosis [1,2]. Their pathogenicity is markedly influenced by a complex network of ‘intra’ and ‘inter-specific’ chemical communication mechanisms belonging to the so-called quorum sensing systems (QS) [3,4]. Each QS is characterized by a signal compound, named quorum sensing molecule (QSM), that is produced by a synthase (I-protein), released into the environment and specifically recognized by a receptor (R-protein) of other microorganisms of the same species present in the same niche [4]. This allows the whole population of microorganisms to produce a unique common synchronized biosynthetic response only when the QSM concentration reaches a specific threshold. Several classes of compounds have been identified as quorum sensing molecules in different bacterial species, such as peptide-pheromones, N-acyl-homoserine lactones (AHLs), interconvertible furanones, hormones, quinolones and fatty acids [5]. AHLs are the most common and well-characterized gram-negative bacterial autoinducers: they can vary in acyl chain length from C4 to C18 and, depending on the bacterial species and the QS network involved, they can present unsaturation at the C-7 or C-8 position and/or oxidation at the 3 position [6].

The Materials and Methods are reported in details in Supporting information S1 Material and methods. Here are indicated the titles of the chapters of that section, and for some of them is reported a brief description of the procedures adopted.

In the present study we investigated whether vertebrate OBPs might exhibit antimicrobial activity against Candida albicans, Pseudomonas aeruginosa and other pathogenic microorganisms.




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