Abstract
Modification of outer membrane proteins (OMPs) is the first line of Gram-negative bacteria defence against antimicrobials. Here we point to Proteus mirabilis OMPs and their role in antibiotic and phage resistance. Protein profiles of amikacin (AMKrsv), phage (Brsv) and amikacin/phage (AMK/Brsv) resistant variants of P. mirabilis were compared to that obtained for a wild strain. In resistant variants there were identified 14, 1, 5 overexpressed and 13, 5, 1 downregulated proteins for AMKrsv, Brsv and AMK/Brsv, respectively. Application of phages with amikacin led to reducing the number of up- and downregulated proteins compared to single antibiotic treatment. Proteins isolated in AMKrsv are involved in protein biosynthesis, transcription and signal transduction, which correspond to well-known mechanisms of bacteria resistance to aminoglycosides. In isolated OMPs several cytoplasmic proteins, important in antibiotic resistance, were identified, probably as a result of environmental stress, e.g. elongation factor Tu, asparaginyl-tRNA and aspartyl-tRNA synthetases. In Brsv there were identified: NusA and dynamin superfamily protein which could play a role in bacteriophage resistance. In the resistant variants proteins associated with resistance mechanisms occurring in biofilm, e.g. polyphosphate kinase, flagella basal body rod protein were detected. These results indicate proteins important in the development of P. mirabilis antibiofilm therapies.
Highlights
Modification of outer membrane proteins (OMPs) is the first line of Gram-negative bacteria defence against antimicrobials
It results in a disruption of the cytoplasmic membrane integrity and allows penetration of a large amount of the antibiotic into the bacterial cell, which leads to the formation of a large amount of abnormal proteins and, cell d eath[11]
Based on the obtained results, the amikacin concentration of 16 μg/mL was used for the selection of resistant variants
Summary
Modification of outer membrane proteins (OMPs) is the first line of Gram-negative bacteria defence against antimicrobials. The potential of a combined use of bacteriophages and antibiotics in biofilms eradication has been previously tested and a significant biofilm disruption and reduction of the resistant variants in Klebsiella pneumoniae or E. coli formation has been observed[5,8,9,10]. Because of their polycationic nature, aminoglycosides, bind to the anionic compounds of the bacterial cell wall. In Gram-negative bacteria it could be a lipopolysaccharide, phospholipids and outer membrane proteins (OMPs) This process is energy-independent and leads to an increase in permeability and to the so called. The modification of OMPs in Gram-negative bacteria could result in the loss or alteration of the phage receptor, which prevents phage adsorption and leads to the inhibition of infection[6]
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