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Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic, multidrug-resistant pathogen capable of adapting to numerous environmental conditions and causing fatal infections in immunocompromised patients. The predominant lifestyle of P. aeruginosa is in the form of biofilms, which are structured communities of bac...

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Autores principales: Ruhal, Rohit, Ghosh, Moumita, Kumar, Vineet, Jain, Deepti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Microbiology Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569066/
https://www.ncbi.nlm.nih.gov/pubmed/37702709
http://dx.doi.org/10.1099/mic.0.001392
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author Ruhal, Rohit
Ghosh, Moumita
Kumar, Vineet
Jain, Deepti
author_facet Ruhal, Rohit
Ghosh, Moumita
Kumar, Vineet
Jain, Deepti
author_sort Ruhal, Rohit
collection PubMed
description Pseudomonas aeruginosa is an opportunistic, multidrug-resistant pathogen capable of adapting to numerous environmental conditions and causing fatal infections in immunocompromised patients. The predominant lifestyle of P. aeruginosa is in the form of biofilms, which are structured communities of bacteria encapsulated in a matrix containing exopolysaccharides, extracellular DNA (eDNA) and proteins. The matrix is impervious to antibiotics, rendering the bacteria tolerant to antimicrobials. P. aeruginosa also produces a plethora of virulence factors such as pyocyanin, rhamnolipids and lipopolysaccharides among others. In this study we present the molecular characterization of pslC and pslI genes, of the exopolysaccharide operon, that code for putative glycosyltransferases. PslC is a 303 amino acid containing putative GT2 glycosyltrasferase, whereas PslI is a 367 aa long protein, possibly functioning as a GT4 glycosyltransferase. Mutation in either of these two genes results in a significant reduction in biofilm biomass with concomitant decline in c-di-GMP levels in the bacterial cells. Moreover, mutation in pslC and pslI dramatically increased susceptibility of P. aeruginosa to tobramycin, colistin and ciprofloxacin. Additionally, these mutations also resulted in an increase in rhamnolipids and pyocyanin formation. We demonstrate that elevated rhamnolipids promote a swarming phenotype in the mutant strains. Together these results highlight the importance of PslC and PslI in the biogenesis of biofilms and their potential as targets for increased antibiotic susceptibility and biofilm inhibition.
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spelling pubmed-105690662023-10-13 Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa Ruhal, Rohit Ghosh, Moumita Kumar, Vineet Jain, Deepti Microbiology (Reading) Microbial Physiology, Biochemistry and Metabolism (formerly Physiology and Metabolism) Pseudomonas aeruginosa is an opportunistic, multidrug-resistant pathogen capable of adapting to numerous environmental conditions and causing fatal infections in immunocompromised patients. The predominant lifestyle of P. aeruginosa is in the form of biofilms, which are structured communities of bacteria encapsulated in a matrix containing exopolysaccharides, extracellular DNA (eDNA) and proteins. The matrix is impervious to antibiotics, rendering the bacteria tolerant to antimicrobials. P. aeruginosa also produces a plethora of virulence factors such as pyocyanin, rhamnolipids and lipopolysaccharides among others. In this study we present the molecular characterization of pslC and pslI genes, of the exopolysaccharide operon, that code for putative glycosyltransferases. PslC is a 303 amino acid containing putative GT2 glycosyltrasferase, whereas PslI is a 367 aa long protein, possibly functioning as a GT4 glycosyltransferase. Mutation in either of these two genes results in a significant reduction in biofilm biomass with concomitant decline in c-di-GMP levels in the bacterial cells. Moreover, mutation in pslC and pslI dramatically increased susceptibility of P. aeruginosa to tobramycin, colistin and ciprofloxacin. Additionally, these mutations also resulted in an increase in rhamnolipids and pyocyanin formation. We demonstrate that elevated rhamnolipids promote a swarming phenotype in the mutant strains. Together these results highlight the importance of PslC and PslI in the biogenesis of biofilms and their potential as targets for increased antibiotic susceptibility and biofilm inhibition. Microbiology Society 2023-09-13 /pmc/articles/PMC10569066/ /pubmed/37702709 http://dx.doi.org/10.1099/mic.0.001392 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License.
spellingShingle Microbial Physiology, Biochemistry and Metabolism (formerly Physiology and Metabolism)
Ruhal, Rohit
Ghosh, Moumita
Kumar, Vineet
Jain, Deepti
Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa
title Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa
title_full Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa
title_fullStr Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa
title_full_unstemmed Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa
title_short Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa
title_sort mutation of putative glycosyl transferases pslc and psli confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in pseudomonas aeruginosa
topic Microbial Physiology, Biochemistry and Metabolism (formerly Physiology and Metabolism)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569066/
https://www.ncbi.nlm.nih.gov/pubmed/37702709
http://dx.doi.org/10.1099/mic.0.001392
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