Molecular Epidemiology and Mechanisms of Tigecycline Resistance in Clinical Isolates of Acinetobacter baumannii from a Chinese University Hospital

Deng, Mei; Zhu, Man; Li, Junjie; Bi, Sheng; Sheng, Zhonghua; Hu, Fei-Shu; Zhang, Jiajie; Chen, Wei; Xue, Xiaowei; Sheng, Jifang; Li, Lanjuan

doi:10.1128/aac.01727-13

Cited by 162 publications

(155 citation statements)

References 37 publications

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“…Tet(X) and Tet(56) are of particular interest due to their clinical significance. tet (X) has been recently identified in a number of human pathogens, including 11 nosocomial uropathogens from Sierra Leone 46 and 12 Acinetobacter baumannii isolates from a hospital in China 47 . We also showed that tet (56) is present and functional in L. longbeachae 28 – a pathogen responsible for causing Pontiac Fever and Legionnaires' Disease 32,33 .…”

Section: Resultsmentioning

confidence: 99%

“…These newer drugs are designed to evade resistance by efflux or ribosomal protection, but they are largely untested against tetracycline-inactivating enzymes. Alarmingly, tigecycline was found to be vulnerable to oxidative inactivation by Tet(X) 27 , which was recently identified for the first time in numerous pathogens of high clinical concern 46,47 . These challenges highlight the immediate importance of studying mechanisms of emerging tetracycline resistance, such as those described here that expand substrate scope.…”

Section: Discussionmentioning

confidence: 99%

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Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

et al. 2017

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While tetracyclines are an important class of antibiotics in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently-discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes with a high potential for broad dissemination. Here, we show tetracycline destructases accommodate tetracycline-class antibiotics in diverse and novel orientations for catalysis, and antibiotic binding drives unprecedented structural dynamics facilitating tetracycline inactivation. We identify a key inhibitor binding mode that locks the flavin adenine dinucleotide cofactor in an inactive state, functionally rescuing tetracycline activity. Our results reveal the potential of a novel tetracycline/tetracycline destructase inhibitor combination therapy strategy to overcome resistance by enzymatic inactivation and restore the use of an important class of antibiotics.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

et al. 2017

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“…In A. baumannii, the AdeABC efflux pump is the major efflux mechanism, and increased expression of the adeABC genes confers resistance to b-lactams, including carbapenems, aminoglycosides and tigecycline, and decreased susceptibility to fluoroquinolones, tetracycline, chloramphenicol, erythromycin, trimethoprim and netilmicin (Deng et al, 2014;Hou et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

“…DNA extraction was performed using a QIAcube system (Qiagen), according to the instructions of the manufacturer. Detection by PCR was performed for OXA type (bla , bla OXA-24 , bla OXA-51 and bla OXA-58 ) carbapenemase genes (Woodford et al, 2006), and resistance genes associated with tigecycline (adeB, tetX1/tetX2) and colistin (pmrB) resistance (Bartha et al, 2011;Deng et al, 2014;Hou et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

“…Colistin resistance is associated with specific modification of the lipid A component of the outer membrane and is mediated by mutations in specific regions of the two-component regulation systems pmrA/B and phoP/Q (Beceiro et al, 2011). Tigecycline resistance has been associated with overexpression of a variety of efflux pumps (Deng et al, 2014;Hou et al, 2012). The presence of the tetX1 gene has also been associated with resistance to tigecycline (Bartha et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Molecular identification of tigecycline- and colistin-resistant carbapenemase-producing Acinetobacter baumannii from a Greek hospital from 2011 to 2013

Mavroidi¹,

Likousi²,

Palla³

et al. 2015

Journal of Medical Microbiology

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An alarming increase in the resistance rates of tigecycline and colistin among carbapenemaseproducing Acinetobacter baumannii recovered from a Greek hospital over a 3-year period (2011-2013) was investigated. The antimicrobial resistance profiles and carbapenemase gene content were determined for a collection of colistin-and/or tigecycline-resistant carbapenemase-producing A. baumannii isolates (n542), which were recovered consecutively during the study period. A gradual increase in the incidence of bla OXA-23 producers was observed from 2011 to 2013. A cluster of 21 isolates comprised tigecycline-resistant bla OXA-23 producers displayed a single antimicrobial resistance pattern. The emergence of two bla OXA-23 producers resistant to both tigecycline and colistin was documented. Furthermore, determination of the mechanisms of colistin and tigecycline resistance and molecular typing by the tri-locus sequence typing (3LST) scheme for nine isolates recovered from bloodstream infections were performed. Out of nine isolates, five tigecycline-and two colistin-resistant isolates were bla OXA-23 producers of 3LST ST101 corresponding to the international clone II recovered during 2012-2013. All nine isolates were positive for the presence of the adeB gene of the AdeABC efflux pump. Three colistin-resistant isolates possessed novel substitutions in PmrB, which may be implicated in colistin resistance. To the best of our knowledge, this is the first report of the acquisition of tigecycline and colistin resistance among bla OXA-23 -producing A. baumannii of 3LST ST101 in Greece; thus, continuous surveillance and molecular characterization, prudent use of antibiotics and implementation of infection control measures for A. baumannii are urgent.

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Emerging High‐Level Tigecycline Resistance: Novel Tetracycline Destructases Spread via the Mobile Tet(X)

Chen

Cui

et al. 2020

BioEssays

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Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next‐generation tetracycline that is the final line of defense against severe infections by pan‐drug‐resistant bacterial pathogens. Unfortunately, this last‐resort antibiotic has been challenged by the recent emergence of the mobile Tet(X) orthologs that can confer high‐level tigecycline resistance. As it is reviewed here, these novel tetracycline destructases represent a growing threat to the next‐generation tetracyclines, and a basic framework for understanding the molecular epidemiology and resistance mechanisms of them is presented. However, further large‐scale epidemiological and functional studies are urgently needed to better understand the prevalence and dissemination of these newly discovered Tet(X) orthologs among Gram‐negative bacteria in both human and veterinary medicine.

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Molecular Epidemiology and Mechanisms of Tigecycline Resistance in Clinical Isolates of Acinetobacter baumannii from a Chinese University Hospital

Cited by 162 publications

References 37 publications

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

Molecular identification of tigecycline- and colistin-resistant carbapenemase-producing Acinetobacter baumannii from a Greek hospital from 2011 to 2013

Emerging High‐Level Tigecycline Resistance: Novel Tetracycline Destructases Spread via the Mobile Tet(X)

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