Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide

Markus H.K. Johansson; Thomas N. Petersen; Sidsel Nag; Timmie M.R. Lagermann; Laura E.K. Birkedahl; Silva Tafaj; Susan Bradbury; Peter Collignon; Denise Daley; Victorien Dougnon; Kafayath Fabiyi; Boubacar Coulibaly; Réné Dembélé; Natama Magloire; Isidore J. Ouindgueta; Zenat Z. Hossain; Anowara Begoum; Deyan Donchev; Mathew Diggle; Lee Ann Turnbull; Simon Lévesque; Livia Berlinger; Kirstine K. Søgaard; Paula D. Guevara; Carolina Duarte; Panagiota Maikanti; Jana Amlerova; Pavel Drevinek; Jan Tkadlec; Milica Dilas; Achim Kaasch; Henrik T. Westh; Mohamed A. Bachtarzi; Wahiba Amhis; Carolina E.S. Salazar; José E. Villacis; Mária A.D. Lúzon; Dàmaris B. Palau; Claire Duployez; Maxime Paluche; Solomon Asante-Sefa; Mie Møller; Margaret Ip; Ivana Mareković; Agnes Pál-Sonnevend; Clementiza E. Cocuzza; Asta Dambrauskiene; Alexandre Macanze; Anelsio Cossa; Inácio Mandomando; Philip Nwajiobi-Princewill; Iruka N. Okeke; Aderemi O. Kehinde; Ini Adebiyi; Ifeoluwa Akintayo; Oluwafemi Popoola; Anthony Onipede; Anita Blomfeldt; Nora E. Nyquist; Kiri Bocker; James Ussher; Amjad Ali; Nimat Ullah; Habibullah Khan; Natalie W. Gustafson; Ikhlas Jarrar; Arif Al-Hamad; Viravarn Luvira; Wantana Paveenkittiporn; Irmak Baran; James C.L. Mwansa; Linda Sikakwa; Kaunda Yamba; Frank M. Aarestrup

doi:10.1371/journal.pone.0330304

Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide

Markus H.K. Johansson^*
, Thomas N. Petersen
, Sidsel Nag
, Timmie M.R. Lagermann
, Laura E.K. Birkedahl
, Silva Tafaj
, Susan Bradbury
, Peter Collignon
, Denise Daley
, Victorien Dougnon
, Kafayath Fabiyi
, Boubacar Coulibaly
, Réné Dembélé
, Natama Magloire
, Isidore J. Ouindgueta
, Zenat Z. Hossain
, Anowara Begoum
, Deyan Donchev
, Mathew Diggle
, Lee Ann Turnbull

Simon Lévesque, Livia Berlinger, Kirstine K. Søgaard, Paula D. Guevara, Carolina Duarte, Panagiota Maikanti, Jana Amlerova, Pavel Drevinek, Jan Tkadlec, Milica Dilas, Achim Kaasch, Henrik T. Westh, Mohamed A. Bachtarzi, Wahiba Amhis, Carolina E.S. Salazar, José E. Villacis, Mária A.D. Lúzon, Dàmaris B. Palau, Claire Duployez, Maxime Paluche, Solomon Asante-Sefa, Mie Møller, Margaret Ip, Ivana Mareković, Agnes Pál-Sonnevend, Clementiza E. Cocuzza, Asta Dambrauskiene, Alexandre Macanze, Anelsio Cossa, Inácio Mandomando, Philip Nwajiobi-Princewill, Iruka N. Okeke, Aderemi O. Kehinde, Ini Adebiyi, Ifeoluwa Akintayo, Oluwafemi Popoola, Anthony Onipede, Anita Blomfeldt, Nora E. Nyquist, Kiri Bocker, James Ussher, Amjad Ali, Nimat Ullah, Habibullah Khan, Natalie W. Gustafson, Ikhlas Jarrar, Arif Al-Hamad, Viravarn Luvira, Wantana Paveenkittiporn, Irmak Baran, James C.L. Mwansa, Linda Sikakwa, Kaunda Yamba, Frank M. Aarestrup

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

Objectives
Antimicrobial-resistant bacteria are a major global health threat. Mobile genetic elements (MGEs) have been crucial for spreading resistance to new bacterial species, including human pathogens. Understanding how MGEs promote resistance could be essential for prevention. Here we present an investigation of MGEs and their association with resistance genes in pathogenic bacteria collected from 59 diagnostic units during 2020, representing a snapshot of clinical infections from 35 counties worldwide.

Methods
We analysed 3,095 whole-genome sequenced clinical bacterial isolates from over 100 species to study the relationship between resistance genes and MGEs. The mobiliome of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae were further examined for geographic differences, as these species were prevalent in all countries. Genes potentially mobilized by MGEs were identified by finding DNA segments containing MGEs and ARGs preserved in multiple species. Network analysis was used to investigate potential MGE interactions, host range, and transmission pathways.

Results
The prevalence and diversity of MGEs and resistance genes varied among species, with E. coli and S. aureus carrying more diverse elements. MGE composition differed between bacterial lineages, indicating strong vertical inheritance. 102 MGEs associated with resistance were found in multiple species, and four of these elements seemed to be highly transmissible as they were found in different phyla. We identified 21 genomic regions containing resistance genes potentially mobilized by MGEs, highlighting their importance in transmitting genes to clinically significant bacteria.

Conclusion
Resistance genes are spread through various MGEs, including plasmids and transposons. Our findings suggest that multiple factors influence MGE prevalence and their transposability, thereby shaping the MGE population and transmission pathways. Some MGEs have a wider host range, which could make them more important for mobilizing genes. We also identified 103 resistance genes potentially mobilised by MGEs, which could increase their transmissibility to unrelated bacteria.

Original language	English
Article number	e0330304
Journal	PLOS ONE
Volume	20
Issue number	8
Number of pages	20
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0330304
Publication status	Published - 2025

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SDG 3 Good Health and Well-being

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Johansson, M. H. K., Petersen, T. N., Nag, S., Lagermann, T. M. R., Birkedahl, L. E. K., Tafaj, S., Bradbury, S., Collignon, P., Daley, D., Dougnon, V., Fabiyi, K., Coulibaly, B., Dembélé, R., Magloire, N., Ouindgueta, I. J., Hossain, Z. Z., Begoum, A., Donchev, D., Diggle, M., ... Aarestrup, F. M. (2025). Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide. PLOS ONE, 20(8), Article e0330304. https://doi.org/10.1371/journal.pone.0330304

@article{9d580316db0f4f20903c2b65fc2734b0,

title = "Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide",

abstract = "Objectives Antimicrobial-resistant bacteria are a major global health threat. Mobile genetic elements (MGEs) have been crucial for spreading resistance to new bacterial species, including human pathogens. Understanding how MGEs promote resistance could be essential for prevention. Here we present an investigation of MGEs and their association with resistance genes in pathogenic bacteria collected from 59 diagnostic units during 2020, representing a snapshot of clinical infections from 35 counties worldwide. Methods We analysed 3,095 whole-genome sequenced clinical bacterial isolates from over 100 species to study the relationship between resistance genes and MGEs. The mobiliome of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae were further examined for geographic differences, as these species were prevalent in all countries. Genes potentially mobilized by MGEs were identified by finding DNA segments containing MGEs and ARGs preserved in multiple species. Network analysis was used to investigate potential MGE interactions, host range, and transmission pathways. Results The prevalence and diversity of MGEs and resistance genes varied among species, with E. coli and S. aureus carrying more diverse elements. MGE composition differed between bacterial lineages, indicating strong vertical inheritance. 102 MGEs associated with resistance were found in multiple species, and four of these elements seemed to be highly transmissible as they were found in different phyla. We identified 21 genomic regions containing resistance genes potentially mobilized by MGEs, highlighting their importance in transmitting genes to clinically significant bacteria. Conclusion Resistance genes are spread through various MGEs, including plasmids and transposons. Our findings suggest that multiple factors influence MGE prevalence and their transposability, thereby shaping the MGE population and transmission pathways. Some MGEs have a wider host range, which could make them more important for mobilizing genes. We also identified 103 resistance genes potentially mobilised by MGEs, which could increase their transmissibility to unrelated bacteria.",

author = "Johansson, \{Markus H.K.\} and Petersen, \{Thomas N.\} and Sidsel Nag and Lagermann, \{Timmie M.R.\} and Birkedahl, \{Laura E.K.\} and Silva Tafaj and Susan Bradbury and Peter Collignon and Denise Daley and Victorien Dougnon and Kafayath Fabiyi and Boubacar Coulibaly and R{\'e}n{\'e} Demb{\'e}l{\'e} and Natama Magloire and Ouindgueta, \{Isidore J.\} and Hossain, \{Zenat Z.\} and Anowara Begoum and Deyan Donchev and Mathew Diggle and Turnbull, \{Lee Ann\} and Simon L{\'e}vesque and Livia Berlinger and S{\o}gaard, \{Kirstine K.\} and Guevara, \{Paula D.\} and Carolina Duarte and Panagiota Maikanti and Jana Amlerova and Pavel Drevinek and Jan Tkadlec and Milica Dilas and Achim Kaasch and Westh, \{Henrik T.\} and Bachtarzi, \{Mohamed A.\} and Wahiba Amhis and Salazar, \{Carolina E.S.\} and Villacis, \{Jos{\'e} E.\} and L{\'u}zon, \{M{\'a}ria A.D.\} and Palau, \{D{\`a}maris B.\} and Claire Duployez and Maxime Paluche and Solomon Asante-Sefa and Mie M{\o}ller and Margaret Ip and Ivana Marekovi{\'c} and Agnes P{\'a}l-Sonnevend and Cocuzza, \{Clementiza E.\} and Asta Dambrauskiene and Alexandre Macanze and Anelsio Cossa and In{\'a}cio Mandomando and Philip Nwajiobi-Princewill and Okeke, \{Iruka N.\} and Kehinde, \{Aderemi O.\} and Ini Adebiyi and Ifeoluwa Akintayo and Oluwafemi Popoola and Anthony Onipede and Anita Blomfeldt and Nyquist, \{Nora E.\} and Kiri Bocker and James Ussher and Amjad Ali and Nimat Ullah and Habibullah Khan and Gustafson, \{Natalie W.\} and Ikhlas Jarrar and Arif Al-Hamad and Viravarn Luvira and Wantana Paveenkittiporn and Irmak Baran and Mwansa, \{James C.L.\} and Linda Sikakwa and Kaunda Yamba and Aarestrup, \{Frank M.\}",

note = "Publisher Copyright: {\textcopyright} 2025 Johansson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2025",

doi = "10.1371/journal.pone.0330304",

language = "English",

volume = "20",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "8",

}

Johansson, MHK, Petersen, TN, Nag, S, Lagermann, TMR, Birkedahl, LEK, Tafaj, S, Bradbury, S, Collignon, P, Daley, D, Dougnon, V, Fabiyi, K, Coulibaly, B, Dembélé, R, Magloire, N, Ouindgueta, IJ, Hossain, ZZ, Begoum, A, Donchev, D, Diggle, M, Turnbull, LA, Lévesque, S, Berlinger, L, Søgaard, KK, Guevara, PD, Duarte, C, Maikanti, P, Amlerova, J, Drevinek, P, Tkadlec, J, Dilas, M, Kaasch, A, Westh, HT, Bachtarzi, MA, Amhis, W, Salazar, CES, Villacis, JE, Lúzon, MAD, Palau, DB, Duployez, C, Paluche, M, Asante-Sefa, S, Møller, M, Ip, M, Mareković, I, Pál-Sonnevend, A, Cocuzza, CE, Dambrauskiene, A, Macanze, A, Cossa, A, Mandomando, I, Nwajiobi-Princewill, P, Okeke, IN, Kehinde, AO, Adebiyi, I, Akintayo, I, Popoola, O, Onipede, A, Blomfeldt, A, Nyquist, NE, Bocker, K, Ussher, J, Ali, A, Ullah, N, Khan, H, Gustafson, NW, Jarrar, I, Al-Hamad, A, Luvira, V, Paveenkittiporn, W, Baran, I, Mwansa, JCL, Sikakwa, L, Yamba, K & Aarestrup, FM 2025, 'Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide', PLOS ONE, vol. 20, no. 8, e0330304. https://doi.org/10.1371/journal.pone.0330304

TY - JOUR

T1 - Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide

AU - Johansson, Markus H.K.

AU - Petersen, Thomas N.

AU - Nag, Sidsel

AU - Lagermann, Timmie M.R.

AU - Birkedahl, Laura E.K.

AU - Tafaj, Silva

AU - Bradbury, Susan

AU - Collignon, Peter

AU - Daley, Denise

AU - Dougnon, Victorien

AU - Fabiyi, Kafayath

AU - Coulibaly, Boubacar

AU - Dembélé, Réné

AU - Magloire, Natama

AU - Ouindgueta, Isidore J.

AU - Hossain, Zenat Z.

AU - Begoum, Anowara

AU - Donchev, Deyan

AU - Diggle, Mathew

AU - Turnbull, Lee Ann

AU - Lévesque, Simon

AU - Berlinger, Livia

AU - Søgaard, Kirstine K.

AU - Guevara, Paula D.

AU - Duarte, Carolina

AU - Maikanti, Panagiota

AU - Amlerova, Jana

AU - Drevinek, Pavel

AU - Tkadlec, Jan

AU - Dilas, Milica

AU - Kaasch, Achim

AU - Westh, Henrik T.

AU - Bachtarzi, Mohamed A.

AU - Amhis, Wahiba

AU - Salazar, Carolina E.S.

AU - Villacis, José E.

AU - Lúzon, Mária A.D.

AU - Palau, Dàmaris B.

AU - Duployez, Claire

AU - Paluche, Maxime

AU - Asante-Sefa, Solomon

AU - Møller, Mie

AU - Ip, Margaret

AU - Mareković, Ivana

AU - Pál-Sonnevend, Agnes

AU - Cocuzza, Clementiza E.

AU - Dambrauskiene, Asta

AU - Macanze, Alexandre

AU - Cossa, Anelsio

AU - Mandomando, Inácio

AU - Nwajiobi-Princewill, Philip

AU - Okeke, Iruka N.

AU - Kehinde, Aderemi O.

AU - Adebiyi, Ini

AU - Akintayo, Ifeoluwa

AU - Popoola, Oluwafemi

AU - Onipede, Anthony

AU - Blomfeldt, Anita

AU - Nyquist, Nora E.

AU - Bocker, Kiri

AU - Ussher, James

AU - Ali, Amjad

AU - Ullah, Nimat

AU - Khan, Habibullah

AU - Gustafson, Natalie W.

AU - Jarrar, Ikhlas

AU - Al-Hamad, Arif

AU - Luvira, Viravarn

AU - Paveenkittiporn, Wantana

AU - Baran, Irmak

AU - Mwansa, James C.L.

AU - Sikakwa, Linda

AU - Yamba, Kaunda

AU - Aarestrup, Frank M.

N1 - Publisher Copyright: © 2025 Johansson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2025

Y1 - 2025

N2 - Objectives Antimicrobial-resistant bacteria are a major global health threat. Mobile genetic elements (MGEs) have been crucial for spreading resistance to new bacterial species, including human pathogens. Understanding how MGEs promote resistance could be essential for prevention. Here we present an investigation of MGEs and their association with resistance genes in pathogenic bacteria collected from 59 diagnostic units during 2020, representing a snapshot of clinical infections from 35 counties worldwide. Methods We analysed 3,095 whole-genome sequenced clinical bacterial isolates from over 100 species to study the relationship between resistance genes and MGEs. The mobiliome of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae were further examined for geographic differences, as these species were prevalent in all countries. Genes potentially mobilized by MGEs were identified by finding DNA segments containing MGEs and ARGs preserved in multiple species. Network analysis was used to investigate potential MGE interactions, host range, and transmission pathways. Results The prevalence and diversity of MGEs and resistance genes varied among species, with E. coli and S. aureus carrying more diverse elements. MGE composition differed between bacterial lineages, indicating strong vertical inheritance. 102 MGEs associated with resistance were found in multiple species, and four of these elements seemed to be highly transmissible as they were found in different phyla. We identified 21 genomic regions containing resistance genes potentially mobilized by MGEs, highlighting their importance in transmitting genes to clinically significant bacteria. Conclusion Resistance genes are spread through various MGEs, including plasmids and transposons. Our findings suggest that multiple factors influence MGE prevalence and their transposability, thereby shaping the MGE population and transmission pathways. Some MGEs have a wider host range, which could make them more important for mobilizing genes. We also identified 103 resistance genes potentially mobilised by MGEs, which could increase their transmissibility to unrelated bacteria.

AB - Objectives Antimicrobial-resistant bacteria are a major global health threat. Mobile genetic elements (MGEs) have been crucial for spreading resistance to new bacterial species, including human pathogens. Understanding how MGEs promote resistance could be essential for prevention. Here we present an investigation of MGEs and their association with resistance genes in pathogenic bacteria collected from 59 diagnostic units during 2020, representing a snapshot of clinical infections from 35 counties worldwide. Methods We analysed 3,095 whole-genome sequenced clinical bacterial isolates from over 100 species to study the relationship between resistance genes and MGEs. The mobiliome of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae were further examined for geographic differences, as these species were prevalent in all countries. Genes potentially mobilized by MGEs were identified by finding DNA segments containing MGEs and ARGs preserved in multiple species. Network analysis was used to investigate potential MGE interactions, host range, and transmission pathways. Results The prevalence and diversity of MGEs and resistance genes varied among species, with E. coli and S. aureus carrying more diverse elements. MGE composition differed between bacterial lineages, indicating strong vertical inheritance. 102 MGEs associated with resistance were found in multiple species, and four of these elements seemed to be highly transmissible as they were found in different phyla. We identified 21 genomic regions containing resistance genes potentially mobilized by MGEs, highlighting their importance in transmitting genes to clinically significant bacteria. Conclusion Resistance genes are spread through various MGEs, including plasmids and transposons. Our findings suggest that multiple factors influence MGE prevalence and their transposability, thereby shaping the MGE population and transmission pathways. Some MGEs have a wider host range, which could make them more important for mobilizing genes. We also identified 103 resistance genes potentially mobilised by MGEs, which could increase their transmissibility to unrelated bacteria.

U2 - 10.1371/journal.pone.0330304

DO - 10.1371/journal.pone.0330304

M3 - Journal article

C2 - 40824964

AN - SCOPUS:105013246707

SN - 1932-6203

VL - 20

JO - PLOS ONE

JF - PLOS ONE

IS - 8

M1 - e0330304

ER -

Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide

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