Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States

Autores
Mojica, Maria F.; Rutter, Joseph D.; Taracila, Magdalena; Abriata, Luciano A.; Fouts, Derrick E.; Papp Wallace, Krisztina M.; Walsh, Thomas J.; LiPuma, John J.; Vila, Alejandro Jose; Bonomo, Robert A.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Stenotrophomonas maltophilia is a Gram-negative, nonfermenting, environmental bacillus that is an important cause of nosocomial infections, primarily associated with the respiratory tract in the immunocompromised population. Aiming to understand the population structure, microbiological characteristics and impact of allelic variation on β-lactamase structure and function, we collected 130 clinical isolates from across the United States. Identification of 90 different sequence types (STs), of which 63 are new allelic combinations, demonstrates the high diversity of this species. The majority of the isolates (45%) belong to genomic group 6. We also report excellent activity of the ceftazidime-avibactam and aztreonam combination, especially against strains recovered from blood and respiratory infections for which the susceptibility is higher than the susceptibility to trimethoprim-sulfamethoxazole, considered the “first-line” antibiotic to treat S. maltophilia. Analysis of 73 blaL1 and 116 blaL2 genes identified 35 and 43 novel variants of L1 and L2 β-lactamases, respectively. Investigation of the derived amino acid sequences showed that substitutions are mostly conservative and scattered throughout the protein, preferentially affecting positions that do not compromise enzyme function but that may have an impact on substrate and inhibitor binding. Interestingly, we detected a probable association between a specific type of L1 and L2 and genomic group 6. Taken together, our results provide an overview of the molecular epidemiology of S. maltophilia clinical strains from the United States. In particular, the discovery of new L1 and L2 variants warrants further study to fully understand the relationship between them and the β-lactam resistance phenotype in this pathogen. IMPORTANCE Multiple antibiotic resistance mechanisms, including two β-lactamases, L1, a metallo-β-lactamase, and L2, a class A cephalosporinase, make S. maltophilia naturally multidrug resistant. Thus, infections caused by S. maltophilia pose a big therapeutic challenge. Our study aims to understand the microbiological and molecular characteristics of S. maltophilia isolates recovered from human sources. A highlight of the resistance profile of this collection is the excellent activity of the ceftazidime-avibactam and aztreonam combination. We hope this result prompts controlled and observational studies to add clinical data on the utility and safety of this therapy. We also identify 35 and 43 novel variants of L1 and L2, respectively, some of which harbor novel substitutions that could potentially affect substrate and/or inhibitor binding. We believe our results provide valuable knowledge to understand the epidemiology of this species and to advance mechanism-based inhibitor design to add to the limited arsenal of antibiotics active against this pathogen.
Fil: Mojica, Maria F.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Fil: Rutter, Joseph D.. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Fil: Taracila, Magdalena. Louis Stokes Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados Unidos
Fil: Abriata, Luciano A.. École Polytechnique Fédérale de Lausanne; Suiza
Fil: Fouts, Derrick E.. J Craig Venter Institute; Estados Unidos
Fil: Papp Wallace, Krisztina M.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Fil: Walsh, Thomas J.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Fil: LiPuma, John J.. University of Michigan; Estados Unidos
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Materia
STENOTROPHOMONAS MALTOPHILIA
METALO BETA LACTAMASAS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/153017

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network_name_str CONICET Digital (CONICET)
spelling Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United StatesMojica, Maria F.Rutter, Joseph D.Taracila, MagdalenaAbriata, Luciano A.Fouts, Derrick E.Papp Wallace, Krisztina M.Walsh, Thomas J.LiPuma, John J.Vila, Alejandro JoseBonomo, Robert A.STENOTROPHOMONAS MALTOPHILIAMETALO BETA LACTAMASAShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Stenotrophomonas maltophilia is a Gram-negative, nonfermenting, environmental bacillus that is an important cause of nosocomial infections, primarily associated with the respiratory tract in the immunocompromised population. Aiming to understand the population structure, microbiological characteristics and impact of allelic variation on β-lactamase structure and function, we collected 130 clinical isolates from across the United States. Identification of 90 different sequence types (STs), of which 63 are new allelic combinations, demonstrates the high diversity of this species. The majority of the isolates (45%) belong to genomic group 6. We also report excellent activity of the ceftazidime-avibactam and aztreonam combination, especially against strains recovered from blood and respiratory infections for which the susceptibility is higher than the susceptibility to trimethoprim-sulfamethoxazole, considered the “first-line” antibiotic to treat S. maltophilia. Analysis of 73 blaL1 and 116 blaL2 genes identified 35 and 43 novel variants of L1 and L2 β-lactamases, respectively. Investigation of the derived amino acid sequences showed that substitutions are mostly conservative and scattered throughout the protein, preferentially affecting positions that do not compromise enzyme function but that may have an impact on substrate and inhibitor binding. Interestingly, we detected a probable association between a specific type of L1 and L2 and genomic group 6. Taken together, our results provide an overview of the molecular epidemiology of S. maltophilia clinical strains from the United States. In particular, the discovery of new L1 and L2 variants warrants further study to fully understand the relationship between them and the β-lactam resistance phenotype in this pathogen. IMPORTANCE Multiple antibiotic resistance mechanisms, including two β-lactamases, L1, a metallo-β-lactamase, and L2, a class A cephalosporinase, make S. maltophilia naturally multidrug resistant. Thus, infections caused by S. maltophilia pose a big therapeutic challenge. Our study aims to understand the microbiological and molecular characteristics of S. maltophilia isolates recovered from human sources. A highlight of the resistance profile of this collection is the excellent activity of the ceftazidime-avibactam and aztreonam combination. We hope this result prompts controlled and observational studies to add clinical data on the utility and safety of this therapy. We also identify 35 and 43 novel variants of L1 and L2, respectively, some of which harbor novel substitutions that could potentially affect substrate and/or inhibitor binding. We believe our results provide valuable knowledge to understand the epidemiology of this species and to advance mechanism-based inhibitor design to add to the limited arsenal of antibiotics active against this pathogen.Fil: Mojica, Maria F.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados UnidosFil: Rutter, Joseph D.. Louis Stokes Veterans Affairs Medical Center; Estados UnidosFil: Taracila, Magdalena. Louis Stokes Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados UnidosFil: Abriata, Luciano A.. École Polytechnique Fédérale de Lausanne; SuizaFil: Fouts, Derrick E.. J Craig Venter Institute; Estados UnidosFil: Papp Wallace, Krisztina M.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados UnidosFil: Walsh, Thomas J.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados UnidosFil: LiPuma, John J.. University of Michigan; Estados UnidosFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados UnidosAmerican Society for Microbiology2019-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/153017Mojica, Maria F.; Rutter, Joseph D.; Taracila, Magdalena; Abriata, Luciano A.; Fouts, Derrick E.; et al.; Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States; American Society for Microbiology; MBio; 10; 4; 7-2019; 1-172150-7511CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/mBio.00405-19info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/mBio.00405-19info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:07Zoai:ri.conicet.gov.ar:11336/153017instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:01:08.154CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States
title Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States
spellingShingle Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States
Mojica, Maria F.
STENOTROPHOMONAS MALTOPHILIA
METALO BETA LACTAMASAS
title_short Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States
title_full Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States
title_fullStr Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States
title_full_unstemmed Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States
title_sort Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States
dc.creator.none.fl_str_mv Mojica, Maria F.
Rutter, Joseph D.
Taracila, Magdalena
Abriata, Luciano A.
Fouts, Derrick E.
Papp Wallace, Krisztina M.
Walsh, Thomas J.
LiPuma, John J.
Vila, Alejandro Jose
Bonomo, Robert A.
author Mojica, Maria F.
author_facet Mojica, Maria F.
Rutter, Joseph D.
Taracila, Magdalena
Abriata, Luciano A.
Fouts, Derrick E.
Papp Wallace, Krisztina M.
Walsh, Thomas J.
LiPuma, John J.
Vila, Alejandro Jose
Bonomo, Robert A.
author_role author
author2 Rutter, Joseph D.
Taracila, Magdalena
Abriata, Luciano A.
Fouts, Derrick E.
Papp Wallace, Krisztina M.
Walsh, Thomas J.
LiPuma, John J.
Vila, Alejandro Jose
Bonomo, Robert A.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv STENOTROPHOMONAS MALTOPHILIA
METALO BETA LACTAMASAS
topic STENOTROPHOMONAS MALTOPHILIA
METALO BETA LACTAMASAS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Stenotrophomonas maltophilia is a Gram-negative, nonfermenting, environmental bacillus that is an important cause of nosocomial infections, primarily associated with the respiratory tract in the immunocompromised population. Aiming to understand the population structure, microbiological characteristics and impact of allelic variation on β-lactamase structure and function, we collected 130 clinical isolates from across the United States. Identification of 90 different sequence types (STs), of which 63 are new allelic combinations, demonstrates the high diversity of this species. The majority of the isolates (45%) belong to genomic group 6. We also report excellent activity of the ceftazidime-avibactam and aztreonam combination, especially against strains recovered from blood and respiratory infections for which the susceptibility is higher than the susceptibility to trimethoprim-sulfamethoxazole, considered the “first-line” antibiotic to treat S. maltophilia. Analysis of 73 blaL1 and 116 blaL2 genes identified 35 and 43 novel variants of L1 and L2 β-lactamases, respectively. Investigation of the derived amino acid sequences showed that substitutions are mostly conservative and scattered throughout the protein, preferentially affecting positions that do not compromise enzyme function but that may have an impact on substrate and inhibitor binding. Interestingly, we detected a probable association between a specific type of L1 and L2 and genomic group 6. Taken together, our results provide an overview of the molecular epidemiology of S. maltophilia clinical strains from the United States. In particular, the discovery of new L1 and L2 variants warrants further study to fully understand the relationship between them and the β-lactam resistance phenotype in this pathogen. IMPORTANCE Multiple antibiotic resistance mechanisms, including two β-lactamases, L1, a metallo-β-lactamase, and L2, a class A cephalosporinase, make S. maltophilia naturally multidrug resistant. Thus, infections caused by S. maltophilia pose a big therapeutic challenge. Our study aims to understand the microbiological and molecular characteristics of S. maltophilia isolates recovered from human sources. A highlight of the resistance profile of this collection is the excellent activity of the ceftazidime-avibactam and aztreonam combination. We hope this result prompts controlled and observational studies to add clinical data on the utility and safety of this therapy. We also identify 35 and 43 novel variants of L1 and L2, respectively, some of which harbor novel substitutions that could potentially affect substrate and/or inhibitor binding. We believe our results provide valuable knowledge to understand the epidemiology of this species and to advance mechanism-based inhibitor design to add to the limited arsenal of antibiotics active against this pathogen.
Fil: Mojica, Maria F.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Fil: Rutter, Joseph D.. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Fil: Taracila, Magdalena. Louis Stokes Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados Unidos
Fil: Abriata, Luciano A.. École Polytechnique Fédérale de Lausanne; Suiza
Fil: Fouts, Derrick E.. J Craig Venter Institute; Estados Unidos
Fil: Papp Wallace, Krisztina M.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Fil: Walsh, Thomas J.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
Fil: LiPuma, John J.. University of Michigan; Estados Unidos
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados Unidos
description Stenotrophomonas maltophilia is a Gram-negative, nonfermenting, environmental bacillus that is an important cause of nosocomial infections, primarily associated with the respiratory tract in the immunocompromised population. Aiming to understand the population structure, microbiological characteristics and impact of allelic variation on β-lactamase structure and function, we collected 130 clinical isolates from across the United States. Identification of 90 different sequence types (STs), of which 63 are new allelic combinations, demonstrates the high diversity of this species. The majority of the isolates (45%) belong to genomic group 6. We also report excellent activity of the ceftazidime-avibactam and aztreonam combination, especially against strains recovered from blood and respiratory infections for which the susceptibility is higher than the susceptibility to trimethoprim-sulfamethoxazole, considered the “first-line” antibiotic to treat S. maltophilia. Analysis of 73 blaL1 and 116 blaL2 genes identified 35 and 43 novel variants of L1 and L2 β-lactamases, respectively. Investigation of the derived amino acid sequences showed that substitutions are mostly conservative and scattered throughout the protein, preferentially affecting positions that do not compromise enzyme function but that may have an impact on substrate and inhibitor binding. Interestingly, we detected a probable association between a specific type of L1 and L2 and genomic group 6. Taken together, our results provide an overview of the molecular epidemiology of S. maltophilia clinical strains from the United States. In particular, the discovery of new L1 and L2 variants warrants further study to fully understand the relationship between them and the β-lactam resistance phenotype in this pathogen. IMPORTANCE Multiple antibiotic resistance mechanisms, including two β-lactamases, L1, a metallo-β-lactamase, and L2, a class A cephalosporinase, make S. maltophilia naturally multidrug resistant. Thus, infections caused by S. maltophilia pose a big therapeutic challenge. Our study aims to understand the microbiological and molecular characteristics of S. maltophilia isolates recovered from human sources. A highlight of the resistance profile of this collection is the excellent activity of the ceftazidime-avibactam and aztreonam combination. We hope this result prompts controlled and observational studies to add clinical data on the utility and safety of this therapy. We also identify 35 and 43 novel variants of L1 and L2, respectively, some of which harbor novel substitutions that could potentially affect substrate and/or inhibitor binding. We believe our results provide valuable knowledge to understand the epidemiology of this species and to advance mechanism-based inhibitor design to add to the limited arsenal of antibiotics active against this pathogen.
publishDate 2019
dc.date.none.fl_str_mv 2019-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/153017
Mojica, Maria F.; Rutter, Joseph D.; Taracila, Magdalena; Abriata, Luciano A.; Fouts, Derrick E.; et al.; Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States; American Society for Microbiology; MBio; 10; 4; 7-2019; 1-17
2150-7511
CONICET Digital
CONICET
url http://hdl.handle.net/11336/153017
identifier_str_mv Mojica, Maria F.; Rutter, Joseph D.; Taracila, Magdalena; Abriata, Luciano A.; Fouts, Derrick E.; et al.; Population Structure, Molecular Epidemiology, and beta-Lactamase Diversity among Stenotrophomonas maltophilia Isolates in the United States; American Society for Microbiology; MBio; 10; 4; 7-2019; 1-17
2150-7511
CONICET Digital
CONICET
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dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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