Essential oils against bacterial isolates from cystic fibrosis patients by means of antimicrobial and unsupervised machine learning approaches

Abstract

Recurrent and chronic respiratory tract infections in cystic fibrosis (CF) patients result in progressive lung damage and represent the primary cause of morbidity and mortality. Staphylococcus aureus (S. aureus) is one of the earliest bacteria in CF infants and children. Starting from early adolescence, patients become chronically infected with Gram-negative non-fermenting bacteria, and Pseudomonas aeruginosa (P. aeruginosa) is the most relevant and recurring. Intensive use of antimicrobial drugs to fight lung infections inevitably leads to the onset of antibiotic resistant bacterial strains. New antimicrobial compounds should be identified to overcome antibiotic resistance in these patients. Recently interesting data were reported in literature on the use of natural derived compounds that inhibited in vitro S. aureus and P. aeruginosa bacterial growth. Essential oils, among these, seemed to be the most promising. In this work is reported an extensive study on 61 essential oils (EOs) against a panel of 40 clinical strains isolated from CF patients. To reduce the in vitro procedure and render the investigation as convergent as possible, machine learning clusterization algorithms were firstly applied to pickup a fewer number of representative strains among the panel of 40. This approach allowed us to easily identify three EOs able to strongly inhibit bacterial growth of all bacterial strains. Interestingly, the EOs antibacterial activity is completely unrelated to the antibiotic resistance profile of each strain. Taking into account the results obtained, a clinical use of EOs could be suggested. Cystic fibrosis (CF), one of the most common lethal genetic disorders in Caucasian population, is inherited as an autosomal recessive disease and affects 70.000 persons worldwide (Cystic Fibrosis Foundation, CFF). The defective gene, identified in 1989, is the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that is carried by 4% of persons (among Caucasians). Since CFTR encodes for a chloride channel of the epithelial cell surface, CF patients manifest a variety of multi-organ problems due to the alteration of sodium and chloride secretion across cell membranes and the subsequent luminal dehydration 1. The impairment of mucociliary clearance, which should remove all microbes entering the airways, leads to the production of a thick and dehydrated mucus in the CF lung, which promotes the airway chronic bacterial colonization 2. The microbiology of CF respiratory tract is peculiar. In the early stage of life, it is characterized by the prevalence of the Gram-positive bacterium Staphylococcus aureus (S. aureus). Overall, in 2017 more than half of affected individuals had at least one culture positive for methicillin sensitive S. aureus (MSSA). The highest prevalence of methicillin resistant S. aureus (MRSA) occurs in individuals between the ages of 10 and 30, while MSSA reaches the peak among patients younger than 10 (Cystic Fibrosis Foundation. 2017. Patient Registry Annual

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