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Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt

Acinetobacter baumannii (A. baumannii) is a highly problematic pathogen with an enormous capacity to acquire or upregulate antibiotic drug resistance determinants. The genomic epidemiology and resistome structure of 46 A. baumannii clinical isolates were studied using whole-genome sequencing. The is...

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Autores principales: Hamed, Samira M., Elkhatib, Walid F., Brangsch, Hanka, Gesraha, Ahmed S., Moustafa, Shawky, Khater, Dalia F., Pletz, Mathias W., Sprague, Lisa D., Neubauer, Heinrich, Wareth, Gamal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376554/
https://www.ncbi.nlm.nih.gov/pubmed/37508245
http://dx.doi.org/10.3390/antibiotics12071149
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author Hamed, Samira M.
Elkhatib, Walid F.
Brangsch, Hanka
Gesraha, Ahmed S.
Moustafa, Shawky
Khater, Dalia F.
Pletz, Mathias W.
Sprague, Lisa D.
Neubauer, Heinrich
Wareth, Gamal
author_facet Hamed, Samira M.
Elkhatib, Walid F.
Brangsch, Hanka
Gesraha, Ahmed S.
Moustafa, Shawky
Khater, Dalia F.
Pletz, Mathias W.
Sprague, Lisa D.
Neubauer, Heinrich
Wareth, Gamal
author_sort Hamed, Samira M.
collection PubMed
description Acinetobacter baumannii (A. baumannii) is a highly problematic pathogen with an enormous capacity to acquire or upregulate antibiotic drug resistance determinants. The genomic epidemiology and resistome structure of 46 A. baumannii clinical isolates were studied using whole-genome sequencing. The isolates were chosen based on reduced susceptibility to at least three classes of antimicrobial compounds and were initially identified using MALDI-TOF/MS, followed by polymerase chain reaction amplification of bla(OXA-51-like) genes. The susceptibility profiles were determined using a broth microdilution assay. Multi-, extensive-, and pan-drug resistance was shown by 34.8%, 63.0%, and 2.2% of the isolates, respectively. These were most susceptible to colistin (95.7%), amikacin, and trimethoprim/sulfamethoxazole (32.6% each), while only 26.1% of isolates were susceptible to tigecycline. In silico multi-locus sequence typing revealed 8 Pasteur and 22 Oxford sequence types (STs) including four novel STs (ST(Oxf) 2805, 2806, 2807, and 2808). The majority of the isolates belonged to Global Clone (GC) 2 (76.4%), GC5 (19.6%), GC4 (6.5%), GC9 (4.3%), and GC7 (2.2%) lineages. An extensive resistome potentially conferring resistance to the majority of the tested antimicrobials was identified in silico. Of all known carbapenem resistance genes, bla(OXA-23) was carried by most of the isolates (69.6%), followed by ISAba1-amplified bla(ADC) (56.5%), bla(NDM-1) and bla(GES-11) (21.7% each), and bla(GES-35) (2.2%) genes. A significant correlation was found between carbapenem resistance and carO mutations, which were evident in 35 (76.0%) isolates. A lower proportion of carbapenem resistance was noted for strains possessing both bla(OXA-23)- and bla(GES-11). Amikacin resistance was most probably mediated by armA, aac(6′)-Ib9, and aph(3′)-VI, most commonly coexisting in GC2 isolates. No mutations were found in pmrABC or lpxACD operons in the colistin-resistant isolates. Tigecycline resistance was associated with adeS (N268Y) and baeS (A436T) mutations. While the lineage-specific distribution of some genes (e.g., bla(ADC) and bla(OXA-51-like) alleles) was evident, some resistance genes, such as bla(OXA-23) and sul1, were found in all GCs. The data generated here highlight the contribution of five GCs in A. baumannii infections in Egypt and enable the comprehensive analysis of GC-specific resistomes, thus revealing the dissemination of the carbapenem resistance gene bla(OXA-23) in isolates encompassing all GCs.
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spelling pubmed-103765542023-07-29 Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt Hamed, Samira M. Elkhatib, Walid F. Brangsch, Hanka Gesraha, Ahmed S. Moustafa, Shawky Khater, Dalia F. Pletz, Mathias W. Sprague, Lisa D. Neubauer, Heinrich Wareth, Gamal Antibiotics (Basel) Article Acinetobacter baumannii (A. baumannii) is a highly problematic pathogen with an enormous capacity to acquire or upregulate antibiotic drug resistance determinants. The genomic epidemiology and resistome structure of 46 A. baumannii clinical isolates were studied using whole-genome sequencing. The isolates were chosen based on reduced susceptibility to at least three classes of antimicrobial compounds and were initially identified using MALDI-TOF/MS, followed by polymerase chain reaction amplification of bla(OXA-51-like) genes. The susceptibility profiles were determined using a broth microdilution assay. Multi-, extensive-, and pan-drug resistance was shown by 34.8%, 63.0%, and 2.2% of the isolates, respectively. These were most susceptible to colistin (95.7%), amikacin, and trimethoprim/sulfamethoxazole (32.6% each), while only 26.1% of isolates were susceptible to tigecycline. In silico multi-locus sequence typing revealed 8 Pasteur and 22 Oxford sequence types (STs) including four novel STs (ST(Oxf) 2805, 2806, 2807, and 2808). The majority of the isolates belonged to Global Clone (GC) 2 (76.4%), GC5 (19.6%), GC4 (6.5%), GC9 (4.3%), and GC7 (2.2%) lineages. An extensive resistome potentially conferring resistance to the majority of the tested antimicrobials was identified in silico. Of all known carbapenem resistance genes, bla(OXA-23) was carried by most of the isolates (69.6%), followed by ISAba1-amplified bla(ADC) (56.5%), bla(NDM-1) and bla(GES-11) (21.7% each), and bla(GES-35) (2.2%) genes. A significant correlation was found between carbapenem resistance and carO mutations, which were evident in 35 (76.0%) isolates. A lower proportion of carbapenem resistance was noted for strains possessing both bla(OXA-23)- and bla(GES-11). Amikacin resistance was most probably mediated by armA, aac(6′)-Ib9, and aph(3′)-VI, most commonly coexisting in GC2 isolates. No mutations were found in pmrABC or lpxACD operons in the colistin-resistant isolates. Tigecycline resistance was associated with adeS (N268Y) and baeS (A436T) mutations. While the lineage-specific distribution of some genes (e.g., bla(ADC) and bla(OXA-51-like) alleles) was evident, some resistance genes, such as bla(OXA-23) and sul1, were found in all GCs. The data generated here highlight the contribution of five GCs in A. baumannii infections in Egypt and enable the comprehensive analysis of GC-specific resistomes, thus revealing the dissemination of the carbapenem resistance gene bla(OXA-23) in isolates encompassing all GCs. MDPI 2023-07-04 /pmc/articles/PMC10376554/ /pubmed/37508245 http://dx.doi.org/10.3390/antibiotics12071149 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hamed, Samira M.
Elkhatib, Walid F.
Brangsch, Hanka
Gesraha, Ahmed S.
Moustafa, Shawky
Khater, Dalia F.
Pletz, Mathias W.
Sprague, Lisa D.
Neubauer, Heinrich
Wareth, Gamal
Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt
title Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt
title_full Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt
title_fullStr Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt
title_full_unstemmed Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt
title_short Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt
title_sort acinetobacter baumannii global clone-specific resistomes explored in clinical isolates recovered from egypt
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376554/
https://www.ncbi.nlm.nih.gov/pubmed/37508245
http://dx.doi.org/10.3390/antibiotics12071149
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