Role of peptidoglycan recycling enzymes AmpD and AnmK in Acinetobacter baumannii virulence features

is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available antibiotics, it is intrinsically resistant to fosfomycin. It has previously been shown that AmpD and AnmK contribute to intrinsic fosfomycin resistance in due to their invo...

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Published in:Frontiers in cellular and infection microbiology Vol. 12; p. 1064053
Main Authors: Tajuelo, Ana, Terrón, María C, López-Siles, Mireia, McConnell, Michael J
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Language:English
Published: Switzerland Frontiers Media S.A 13-01-2023
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Abstract is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available antibiotics, it is intrinsically resistant to fosfomycin. It has previously been shown that AmpD and AnmK contribute to intrinsic fosfomycin resistance in due to their involvement in the peptidoglycan recycling pathway. However, the role that these two enzymes play in the fitness and virulence of has not been studied. The aim of this study was to characterize several virulence-related phenotypic traits in mutants lacking AmpD and AnmK. Specifically, cell morphology, peptidoglycan thickness, membrane permeability, growth under iron-limiting conditions, fitness, resistance to disinfectants and antimicrobial agents, twitching motility and biofilm formation of the mutant strains ATCC 17978 Δ ::Kan and Δ ::Kan were compared to the wild type strain. Our results demonstrate that bacterial growth and fitness of both mutants were compromised, especially in the Δ ::Kan mutant. In addition, biofilm formation was decreased by up to 69%, whereas twitching movement was reduced by about 80% in both mutants. These results demonstrate that, in addition to increased susceptibility to fosfomycin, alteration of the peptidoglycan recycling pathway affects multiple aspects related to virulence. Inhibition of these enzymes could be explored as a strategy to develop novel treatments for in the future. Furthermore, this study establishes a link between intrinsic fosfomycin resistance mechanisms and bacterial fitness and virulence traits.
AbstractList Acinetobacter baumannii is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available antibiotics, it is intrinsically resistant to fosfomycin. It has previously been shown that AmpD and AnmK contribute to intrinsic fosfomycin resistance in A. baumannii due to their involvement in the peptidoglycan recycling pathway. However, the role that these two enzymes play in the fitness and virulence of A. baumannii has not been studied. The aim of this study was to characterize several virulence-related phenotypic traits in A. baumannii mutants lacking AmpD and AnmK. Specifically, cell morphology, peptidoglycan thickness, membrane permeability, growth under iron-limiting conditions, fitness, resistance to disinfectants and antimicrobial agents, twitching motility and biofilm formation of the mutant strains A. baumannii ATCC 17978 ΔampD::Kan and ΔanmK::Kan were compared to the wild type strain. Our results demonstrate that bacterial growth and fitness of both mutants were compromised, especially in the ΔampD::Kan mutant. In addition, biofilm formation was decreased by up to 69%, whereas twitching movement was reduced by about 80% in both mutants. These results demonstrate that, in addition to increased susceptibility to fosfomycin, alteration of the peptidoglycan recycling pathway affects multiple aspects related to virulence. Inhibition of these enzymes could be explored as a strategy to develop novel treatments for A. baumannii in the future. Furthermore, this study establishes a link between intrinsic fosfomycin resistance mechanisms and bacterial fitness and virulence traits.
Acinetobacter baumannii is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available antibiotics, it is intrinsically resistant to fosfomycin. It has previously been shown that AmpD and AnmK contribute to intrinsic fosfomycin resistance in A. baumannii due to their involvement in the peptidoglycan recycling pathway. However, the role that these two enzymes play in the fitness and virulence of A. baumannii has not been studied. The aim of this study was to characterize several virulence-related phenotypic traits in A. baumannii mutants lacking AmpD and AnmK. Specifically, cell morphology, peptidoglycan thickness, membrane permeability, growth under iron-limiting conditions, fitness, resistance to disinfectants and antimicrobial agents, twitching motility and biofilm formation of the mutant strains A. baumannii ATCC 17978 Δ ampD ::Kan and Δ anmK ::Kan were compared to the wild type strain. Our results demonstrate that bacterial growth and fitness of both mutants were compromised, especially in the Δ ampD ::Kan mutant. In addition, biofilm formation was decreased by up to 69%, whereas twitching movement was reduced by about 80% in both mutants. These results demonstrate that, in addition to increased susceptibility to fosfomycin, alteration of the peptidoglycan recycling pathway affects multiple aspects related to virulence. Inhibition of these enzymes could be explored as a strategy to develop novel treatments for A. baumannii in the future. Furthermore, this study establishes a link between intrinsic fosfomycin resistance mechanisms and bacterial fitness and virulence traits.
is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available antibiotics, it is intrinsically resistant to fosfomycin. It has previously been shown that AmpD and AnmK contribute to intrinsic fosfomycin resistance in due to their involvement in the peptidoglycan recycling pathway. However, the role that these two enzymes play in the fitness and virulence of has not been studied. The aim of this study was to characterize several virulence-related phenotypic traits in mutants lacking AmpD and AnmK. Specifically, cell morphology, peptidoglycan thickness, membrane permeability, growth under iron-limiting conditions, fitness, resistance to disinfectants and antimicrobial agents, twitching motility and biofilm formation of the mutant strains ATCC 17978 Δ ::Kan and Δ ::Kan were compared to the wild type strain. Our results demonstrate that bacterial growth and fitness of both mutants were compromised, especially in the Δ ::Kan mutant. In addition, biofilm formation was decreased by up to 69%, whereas twitching movement was reduced by about 80% in both mutants. These results demonstrate that, in addition to increased susceptibility to fosfomycin, alteration of the peptidoglycan recycling pathway affects multiple aspects related to virulence. Inhibition of these enzymes could be explored as a strategy to develop novel treatments for in the future. Furthermore, this study establishes a link between intrinsic fosfomycin resistance mechanisms and bacterial fitness and virulence traits.
Author López-Siles, Mireia
McConnell, Michael J
Tajuelo, Ana
Terrón, María C
AuthorAffiliation 4 Serra Húnter Fellow, Microbiology of Intestinal Diseases, Biology Department, Universitat de Girona , Girona , Spain
3 Electron Microscopy Unit, Scientific-Technical Central Units, Instituto de Salud Carlos III (ISCIII) , Madrid , Spain
2 Universidad Nacional de Educación a Distancia (UNED) , Madrid , Spain
1 Intrahospital Infections Laboratory, Instituto de Salud Carlos III (ISCIII), National Centre for Microbiology , Madrid , Spain
AuthorAffiliation_xml – name: 2 Universidad Nacional de Educación a Distancia (UNED) , Madrid , Spain
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  surname: McConnell
  fullname: McConnell, Michael J
  organization: Intrahospital Infections Laboratory, Instituto de Salud Carlos III (ISCIII), National Centre for Microbiology, Madrid, Spain
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Keywords biofilm formation
Acinetobacter baumannii
disinfectants
fosfomycin resistance
twitching motility
peptidoglycan recycling
Language English
License Copyright © 2023 Tajuelo, Terrón, López-Siles and McConnell.
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Edited by: Paolo Visca, Roma Tre University, Italy
The authors have contributed equally to this work and share senior authorship
This article was submitted to Molecular Bacterial Pathogenesis, a section of the journal Frontiers in Cellular and Infection Microbiology
Reviewed by: Chelsie Armbruster, University at Buffalo, United States; Alessandra Polissi, University of Milan, Italy
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Snippet is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available antibiotics, it is...
Acinetobacter baumannii is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available...
Acinetobacter baumannii is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available...
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StartPage 1064053
SubjectTerms Acinetobacter baumannii
Acinetobacter baumannii - metabolism
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
biofilm formation
Biofilms
Cellular and Infection Microbiology
disinfectants
Drug Resistance, Multiple, Bacterial
Fosfomycin - pharmacology
fosfomycin resistance
Peptidoglycan - metabolism
peptidoglycan recycling
twitching motility
Virulence
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Title Role of peptidoglycan recycling enzymes AmpD and AnmK in Acinetobacter baumannii virulence features
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