AUTHOR=Chen Xiandi , Li Yitan , Lin Yingzhuo , Guo Yingyi , He Guohua , Wang Xiaohu , Wang Mingzhen , Xu Jianbo , Song Mingdong , Tan Xixi , Zhuo Chao , Lin Zhiwei 

TITLE=Comparison of antimicrobial activities and resistance mechanisms of eravacycline and tigecycline against clinical Acinetobacter baumannii isolates in China

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1417237

DOI=10.3389/fmicb.2024.1417237

ISSN=1664-302X

ABSTRACT=<p>Tigecycline (TGC) is currently used to treat carbapenem-resistant <italic>Acinetobacter baumannii</italic> (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 <italic>A. baumannii</italic> remain unclear. This study sought to compare the characteristics and mechanisms of ERV and TGC resistance among clinical <italic>A. baumannii</italic> isolates. A total of 492 isolates, including 253 CRAB and 239 carbapenem-sensitive <italic>A. baumannii</italic> (CSAB) isolates, were collected from hospitalized patients in China. The MICs of ERV and TGC against <italic>A. baumannii</italic> were determined by broth microdilution. Genetic mutations and expressions of <italic>adeB, adeG, adeJ, adeS, adeL</italic>, and <italic>adeN</italic> in resistant strains were examined by PCR and qPCR, respectively. The <italic>in vitro</italic> recombination experiments were used to verify the resistance mechanism of ERV and TGC in <italic>A. baumannii</italic>. The MIC<sub>90</sub> 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 (<italic>n</italic> = 2), both ERV- and TGC-resistant (<italic>n</italic> = 7), and only TGC-resistant (<italic>n</italic> = 15). ST208 (75%, <italic>n</italic> = 18) was a major clone that has disseminated in all three groups. The IS<italic>Aba1</italic> insertion in <italic>adeS</italic> was identified in 66.7% (6/9) of strains in the only ERV-resistant and both ERV- and TGC-resistant groups, while the IS<italic>Aba1</italic> insertion in <italic>adeN</italic> was found in 53.3% (8/15) of strains in the only TGC-resistant group. The <italic>adeABC</italic> and <italic>adeRS</italic> expressions were significantly increased in the only ERV-resistant and both ERV- and TGC-resistant groups, while the <italic>adeABC</italic> and <italic>adeIJK</italic> expressions were significantly increased and <italic>adeN</italic> was significantly decreased in the only TGC-resistant group. Expression of <italic>adeS</italic> with the IS<italic>Aba1</italic> insertion in ERV- and TGC-sensitive strains significantly increased the ERV and TGC MICs and upregulated <italic>adeABC</italic> and <italic>adeRS</italic> expressions. Complementation of the wildtype <italic>adeN</italic> in TGC-resistant strains with the IS<italic>Aba1</italic> insertion in <italic>adeN</italic> restored TGC sensitivity and significantly downregulated <italic>adeIJK</italic> expression. In conclusion, our data illustrates that ERV is more effective against <italic>A. baumannii</italic> clinical isolates than TGC. ERV resistance is correlated with the IS<italic>Aba1</italic> insertion in <italic>adeS</italic>, while TGC resistance is associated with the IS<italic>Aba1</italic> insertion in <italic>adeN</italic> or <italic>adeS</italic> in <italic>A. baumannii.</italic></p>