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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/153017
Ver los metadatos del registro completo
id |
CONICETDig_75a1219c6591c9ea307637d2a05310e0 |
---|---|
oai_identifier_str |
oai:ri.conicet.gov.ar:11336/153017 |
network_acronym_str |
CONICETDig |
repository_id_str |
3498 |
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 http://purl.org/coar/resource_type/c_6501 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 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1128/mBio.00405-19 info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/mBio.00405-19 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Society for Microbiology |
publisher.none.fl_str_mv |
American Society for Microbiology |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
_version_ |
1844613801109880832 |
score |
13.070432 |