Comparison of antimicrobial activities and resistance mechanisms of eravacycline and tigecycline against clinical Acinetobacter baumannii isolates in China
Tigecycline (TGC) is currently used to treat carbapenem-resistant (CRAB) infections, while eravacycline (ERV), a new-generation tetracycline, holds promise as a novel therapeutic option for these infections. However, differences in resistance mechanism between ERV and TGC against remain unclear. Thi...
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Published in: | Frontiers in microbiology Vol. 15; p. 1417237 |
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Main Authors: | , , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
Switzerland
Frontiers Media S.A
24-09-2024
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Subjects: | |
Online Access: | Get full text |
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Summary: | Tigecycline (TGC) is currently used to treat carbapenem-resistant
(CRAB) infections, while eravacycline (ERV), a new-generation tetracycline, holds promise as a novel therapeutic option for these infections. However, differences in resistance mechanism between ERV and TGC against
remain unclear. This study sought to compare the characteristics and mechanisms of ERV and TGC resistance among clinical
isolates. A total of 492 isolates, including 253 CRAB and 239 carbapenem-sensitive
(CSAB) isolates, were collected from hospitalized patients in China. The MICs of ERV and TGC against
were determined by broth microdilution. Genetic mutations and expressions of
, and
in resistant strains were examined by PCR and qPCR, respectively. The
recombination experiments were used to verify the resistance mechanism of ERV and TGC in
. The MIC
of ERV in CRAB and CSAB isolates were lower than those of TGC. A total of 24 strains resistant to ERV and/or TGC were categorized into three groups: only ERV-resistant (
= 2), both ERV- and TGC-resistant (
= 7), and only TGC-resistant (
= 15). ST208 (75%,
= 18) was a major clone that has disseminated in all three groups. The IS
insertion in
was identified in 66.7% (6/9) of strains in the only ERV-resistant and both ERV- and TGC-resistant groups, while the IS
insertion in
was found in 53.3% (8/15) of strains in the only TGC-resistant group. The
and
expressions were significantly increased in the only ERV-resistant and both ERV- and TGC-resistant groups, while the
and
expressions were significantly increased and
was significantly decreased in the only TGC-resistant group. Expression of
with the IS
insertion in ERV- and TGC-sensitive strains significantly increased the ERV and TGC MICs and upregulated
and
expressions. Complementation of the wildtype
in TGC-resistant strains with the IS
insertion in
restored TGC sensitivity and significantly downregulated
expression. In conclusion, our data illustrates that ERV is more effective against
clinical isolates than TGC. ERV resistance is correlated with the IS
insertion in
, while TGC resistance is associated with the IS
insertion in
or
in |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Subhasree Roy, National Institute of Cholera and Enteric Diseases (ICMR), India Edited by: Sulagna Basu, National Institute of Cholera and Enteric Diseases (ICMR), India Reviewed by: Saranya Vijayakumar, Kansas State University, United States These authors have contributed equally to this work |
ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2024.1417237 |