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 |
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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 – name: 1 Intrahospital Infections Laboratory, Instituto de Salud Carlos III (ISCIII), National Centre for Microbiology , Madrid , Spain – name: 3 Electron Microscopy Unit, Scientific-Technical Central Units, Instituto de Salud Carlos III (ISCIII) , Madrid , Spain – name: 4 Serra Húnter Fellow, Microbiology of Intestinal Diseases, Biology Department, Universitat de Girona , Girona , Spain |
Author_xml | – sequence: 1 givenname: Ana surname: Tajuelo fullname: Tajuelo, Ana organization: Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain – sequence: 2 givenname: María C surname: Terrón fullname: Terrón, María C organization: Electron Microscopy Unit, Scientific-Technical Central Units, Instituto de Salud Carlos III (ISCIII), Madrid, Spain – sequence: 3 givenname: Mireia surname: López-Siles fullname: López-Siles, Mireia organization: Serra Húnter Fellow, Microbiology of Intestinal Diseases, Biology Department, Universitat de Girona, Girona, Spain – sequence: 4 givenname: Michael J 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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Cites_doi | 10.1128/AAC.00172-08 10.1038/nrmicro.2017.148 10.1038/nrmicro3525 10.1101/cshperspect.a025262 10.1186/2110-5820-1-14 10.1128/IAI.71.8.4250-4259.2003 10.1111/j.1574-6968.2011.02362.x 10.1111/j.1574-6976.2007.00094.x 10.1016/j.bioorg.2014.05.011 10.3389/fmed.2017.00163 10.1016/j.vaccine.2011.06.001 10.1111/j.1574-6968.2009.01669.x 10.1007/s00018-010-0571-8 10.3109/07388558909036741 10.1016/j.jhin.2011.08.013 10.1016/j.jiac.2016.01.010 10.1099/jmm.0.000636 10.1128/MMBR.00027-07 10.1186/s12866-015-0397-5 10.1007/s11274-018-2542-4 10.1111/j.1462-5822.2004.00443.x 10.1046/j.1365-2958.1999.01339.x 10.1128/JB.185.7.2374-2378.2003 10.1111/j.1574-6976.2012.00344.x 10.1128/AAC.01458-05 10.1074/jbc.M116.751099 10.1073/pnas.2003271117 10.1128/AAC.01314-12 10.1038/nmeth.2019 10.3389/fmicb.2019.00500 10.1186/s12866-020-02083-0 10.1128/microbiolspec.MTBP-0016-2017 10.3389/fcimb.2017.00055 10.1128/jb.179.8.2512-2518.1997 10.1128/AAC.00929-10 10.1111/j.1365-2818.2009.03299.x 10.1128/AEM.00280-20 10.1007/s40121-015-0092-8 10.1517/14656566.2014.914172 10.1038/nchembio.1289 10.1099/jmm.0.000874 10.1089/mdr.2016.0083 10.3390/biom8040122 10.1371/journal.pone.0017027 10.3389/fmicb.2015.00377 10.1093/cid/ciz830 10.1128/mBio.01783-16 10.1038/s41467-021-22849-y 10.1093/jac/dky289 10.3389/fpubh.2021.707435 10.1016/j.ijbiomac.2016.12.082 10.3389/fmicb.2019.00331 10.1111/j.1749-6632.2012.06813.x 10.1080/21505594.2018.1460187 10.1111/j.1365-2958.2005.04892.x 10.1016/j.femsre.2004.09.003 10.12998/wjcc.v2.i12.787 10.7717/peerj.9020 10.1046/j.1365-2958.1998.01062.x |
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Copyright | Copyright © 2023 Tajuelo, Terrón, López-Siles and McConnell. Copyright © 2023 Tajuelo, Terrón, López-Siles and McConnell 2023 Tajuelo, Terrón, López-Siles and McConnell |
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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. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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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Title | Role of peptidoglycan recycling enzymes AmpD and AnmK in Acinetobacter baumannii virulence features |
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