Two strategies to deepen knowledge the antibiotic resistance related traits in Italian MDR Staphylococci: comparative transcriptomic of two DAP-R/DAP-S MRSA isogenic couples and CRISPR system characterization of pathogenic S. epidermidis

Abstract

Antibiotic resistance is worldwide an increasing problem for the public health. Scientists are working to better know the features of Multi-Drug Resistant (MDR) bacteria to develop new strategies to overcome the antibiotic resistance. Among the most common bacteria capable to infect humans and become resistant to antibiotics, the members of the genus Staphylococcus are the etiological agents of some infectious diseases that can be lethal if the pharmacological treatment fails. S. aureus can cause a wide spectrum of diseases, ranging from mild skin forms to systemic forms, whilst S. epidermidis has been frequently implicated in endocarditis and infections of surgical implants and it seems to be the source for antibiotic resistance related gene acquisition by S. aureus. A comparative transcriptomic analysis by RNA-seq and bioinformatic of two Methicillin-Resistant S. aureus isogenic pairs, the characterization of the CRISPR-Cas system and phage infection sensitivity tests of ten Italian pathogenic clinical MDR S. epidermidis strains were performed to deepen knowledge the antibiotic resistance related traits in Italian MDR Staphylococci. Results of transcriptomic analysis showed the contribution of Staphylococcal mRNAs and small-RNAs in daptomycin resistance, with multiple pathways associated, including the cell-wall biosynthesis and organization, metabolism, nucleic acid metabolism, stress response and transport, confirming the role of transcriptome in developing antibiotic resistance. CRISPR-Cas system presence seems to not be a common trait in MDR S. epidermidis (33%) although they showed a high resistance to phage infection, results that should be considered in the perspective of developing a phage therapy. Finally, recent discoveries suggest the possibility to use CRISPR, in the future, to target not only the genes, but also RNAs (messenger and small), linking transcriptome analysis and CRISPR system studies as parts of a possible strategy to cure the antibiotic resistance.