Control of the phage defence mechanisms by Quorum sensing (QS) in clinical isolates of Klebsiella pneumoniae

Multidrug resistant (MDR) bacteria and the shortage of new antibiotics are a serious health problem and have increased the interest in bacteriophages, with great potential as antimicrobial agents but they can induce resistance. The objective of the present study was to reduce the development of phage resistance in K. pneumoniae strains by inhibiting the Quorum Sensing (QS). The QS inhibition by cinnamaldehyde (CAD) was confirmed indirectly by the reduction of biofilm production and directly by a proteomic analysis. Also, the infection assays showed that the phage resistance mechanisms of the bacteria were inhibited when phage-resistant K. pneumoniae strains were treated with a combination of phages with CAD. Finally, these results were confirmed by proteomic analysis as proteins related to the phage defence such as CBASS (bacterial cyclic oligonucleotide-based anti-phage signalling) and R-M systems as well as tail fiber proteins were present under phage treatment but not with the combination. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/570179v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@a97009org.highwire.dtl.DTLVardef@1fa7f02org.highwire.dtl.DTLVardef@a8909corg.highwire.dtl.DTLVardef@ae0284_HPS_FORMAT_FIGEXP M_FIG C_FIG