Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species

ABSTRACT The emergence of the tet(X) gene is a severe challenge to global public health security, as clinical tigecycline resistance shows a rapidly rising trend. In this research, we identified two tigecycline-resistant Acinetobacter sp. strains containing seven novel tet(X3) variants recovered fro...

Full description

Bibliographic Details
Main Authors: Yumeng Cheng, Yakun Li, Runhao Yu, Mingxiang Ma, Meng Yang, Hongbin Si
Format: Article
Language:English
Published: American Society for Microbiology 2022-12-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.01333-22
_version_ 1797978411300290560
author Yumeng Cheng
Yakun Li
Runhao Yu
Mingxiang Ma
Meng Yang
Hongbin Si
author_facet Yumeng Cheng
Yakun Li
Runhao Yu
Mingxiang Ma
Meng Yang
Hongbin Si
author_sort Yumeng Cheng
collection DOAJ
description ABSTRACT The emergence of the tet(X) gene is a severe challenge to global public health security, as clinical tigecycline resistance shows a rapidly rising trend. In this research, we identified two tigecycline-resistant Acinetobacter sp. strains containing seven novel tet(X3) variants recovered from fecal samples from Chinese farms. The seven Tet(X3) variants showed 15.4% to 99.7% amino acid identity with Tet(X3). By expressing tet(X3.7) and tet(X3.9), the tigecycline MIC values for Escherichia coli JM109 increased 64-fold (from 0.13 to 8 mg/L). However, the other tet(X3) variants did not have a significant change in the MIC of tigecycline. We found that the 26th amino acid site of Tet(X3.7) changed from proline to serine, and the 25th amino acid site of Tet(X3.9) changed from glycine to alanine, which reduced the MIC of tigecycline by 2-fold [the MIC of tet(X3) to tigecycline was 16 mg/L] but did not affect its expression to tigecycline. The tet(X3) variants surrounded by mobile genetic elements appeared in the structure of gene clusters with tandem repeat sequences and were adjacent to the site-specific recombinase-encoding gene xerD. Therefore, there is a risk of horizontal transfer of resistant genes. Our study reports seven novel tet(X3) variants; the continuing emergence of tigecycline variants makes continuous monitoring of resistance to tigecycline even more critical. IMPORTANCE Although it is illegal to use tigecycline and carbapenems to treat bacterial infections in animals, we can still isolate bacteria containing both mobile resistance genes from animals, and tet(X) is currently an essential factor in degrading tigecycline. Here, we characterized two multidrug-resistant Acinetobacter sp. strains that contained vital resistance genes, such as sul2, a blaOXA-164-like gene, floR, tetM, and multiple novel tet(X3) variants with different tandem structures. It is of paramount significance that their mechanism may transfer to other Gram-negative pathogens, even if their tandem structures have no cumulative effect on tigecycline resistance.
first_indexed 2024-04-11T05:22:34Z
format Article
id doaj.art-3a2fd25a9cd141108f9e42a4a3ecabc9
institution Directory Open Access Journal
issn 2165-0497
language English
last_indexed 2024-04-11T05:22:34Z
publishDate 2022-12-01
publisher American Society for Microbiology
record_format Article
series Microbiology Spectrum
spelling doaj.art-3a2fd25a9cd141108f9e42a4a3ecabc92022-12-23T15:19:27ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-12-0110610.1128/spectrum.01333-22Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter SpeciesYumeng Cheng0Yakun Li1Runhao Yu2Mingxiang Ma3Meng Yang4Hongbin Si5College of Animal Science and Technology, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, ChinaCollege of Life Science and Technology, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Animal Science and Technology, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, ChinaCollege of Animal Science and Technology, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, ChinaCollege of Animal Science and Technology, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, ChinaABSTRACT The emergence of the tet(X) gene is a severe challenge to global public health security, as clinical tigecycline resistance shows a rapidly rising trend. In this research, we identified two tigecycline-resistant Acinetobacter sp. strains containing seven novel tet(X3) variants recovered from fecal samples from Chinese farms. The seven Tet(X3) variants showed 15.4% to 99.7% amino acid identity with Tet(X3). By expressing tet(X3.7) and tet(X3.9), the tigecycline MIC values for Escherichia coli JM109 increased 64-fold (from 0.13 to 8 mg/L). However, the other tet(X3) variants did not have a significant change in the MIC of tigecycline. We found that the 26th amino acid site of Tet(X3.7) changed from proline to serine, and the 25th amino acid site of Tet(X3.9) changed from glycine to alanine, which reduced the MIC of tigecycline by 2-fold [the MIC of tet(X3) to tigecycline was 16 mg/L] but did not affect its expression to tigecycline. The tet(X3) variants surrounded by mobile genetic elements appeared in the structure of gene clusters with tandem repeat sequences and were adjacent to the site-specific recombinase-encoding gene xerD. Therefore, there is a risk of horizontal transfer of resistant genes. Our study reports seven novel tet(X3) variants; the continuing emergence of tigecycline variants makes continuous monitoring of resistance to tigecycline even more critical. IMPORTANCE Although it is illegal to use tigecycline and carbapenems to treat bacterial infections in animals, we can still isolate bacteria containing both mobile resistance genes from animals, and tet(X) is currently an essential factor in degrading tigecycline. Here, we characterized two multidrug-resistant Acinetobacter sp. strains that contained vital resistance genes, such as sul2, a blaOXA-164-like gene, floR, tetM, and multiple novel tet(X3) variants with different tandem structures. It is of paramount significance that their mechanism may transfer to other Gram-negative pathogens, even if their tandem structures have no cumulative effect on tigecycline resistance.https://journals.asm.org/doi/10.1128/spectrum.01333-22tigecycline resistancetet(X)tet(X3)Acinetobacter variabilisAcinetobacter schindleri
spellingShingle Yumeng Cheng
Yakun Li
Runhao Yu
Mingxiang Ma
Meng Yang
Hongbin Si
Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species
Microbiology Spectrum
tigecycline resistance
tet(X)
tet(X3)
Acinetobacter variabilis
Acinetobacter schindleri
title Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species
title_full Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species
title_fullStr Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species
title_full_unstemmed Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species
title_short Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species
title_sort identification of novel tet x3 variants resistant to tigecycline in acinetobacter species
topic tigecycline resistance
tet(X)
tet(X3)
Acinetobacter variabilis
Acinetobacter schindleri
url https://journals.asm.org/doi/10.1128/spectrum.01333-22
work_keys_str_mv AT yumengcheng identificationofnoveltetx3variantsresistanttotigecyclineinacinetobacterspecies
AT yakunli identificationofnoveltetx3variantsresistanttotigecyclineinacinetobacterspecies
AT runhaoyu identificationofnoveltetx3variantsresistanttotigecyclineinacinetobacterspecies
AT mingxiangma identificationofnoveltetx3variantsresistanttotigecyclineinacinetobacterspecies
AT mengyang identificationofnoveltetx3variantsresistanttotigecyclineinacinetobacterspecies
AT hongbinsi identificationofnoveltetx3variantsresistanttotigecyclineinacinetobacterspecies