TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>

ABSTRACT Carbon metabolism plays an essential role in bacterial pathogenesis and susceptibility to antibiotics. In Pseudomonas aeruginosa, Crc, Hfq, and a small RNA, CrcZ, are central regulators of carbon metabolism. By screening mutants of genes involved in carbon metabolism, we found that mutation...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yushan Xia, Dan Wang, Xiaolei Pan, Bin Xia, Yuding Weng, Yuqing Long, Huan Ren, Jingyi Zhou, Yongxin Jin, Fang Bai, Zhihui Cheng, Shouguang Jin, Weihui Wu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Pseudomonas aeruginosa antibiotic resistance carbon catabolite repression triosephosphate isomerase virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cbf728bb86554fda9f6bb29830423dfc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cbf728bb86554fda9f6bb29830423dfc
record_format	dspace
spelling	oai:doaj.org-article:cbf728bb86554fda9f6bb29830423dfc2021-11-15T15:56:57ZTpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>10.1128/mBio.02079-192150-7511https://doaj.org/article/cbf728bb86554fda9f6bb29830423dfc2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02079-19https://doaj.org/toc/2150-7511ABSTRACT Carbon metabolism plays an essential role in bacterial pathogenesis and susceptibility to antibiotics. In Pseudomonas aeruginosa, Crc, Hfq, and a small RNA, CrcZ, are central regulators of carbon metabolism. By screening mutants of genes involved in carbon metabolism, we found that mutation of the tpiA gene reduces the expression of the type III secretion system (T3SS) and bacterial resistance to aminoglycoside antibiotics. TpiA is a triosephosphate isomerase that reversibly converts glyceraldehyde 3-phosphate to dihydroxyacetone phosphate, a key step connecting glucose metabolism with glycerol and phospholipid metabolisms. We found that mutation of the tpiA gene enhances the bacterial carbon metabolism, respiration, and oxidative phosphorylation, which increases the membrane potential and promotes the uptake of aminoglycoside antibiotics. Further studies revealed that the level of CrcZ is increased in the tpiA mutant due to enhanced stability. Mutation of the crcZ gene in the tpiA mutant background restored the expression of the T3SS genes and the bacterial resistance to aminoglycoside antibiotics. Overall, this study reveals an essential role of TpiA in the metabolism, virulence, and antibiotic resistance in P. aeruginosa. IMPORTANCE The increase in bacterial resistance against antibiotics imposes a severe threat to public health. It is urgent to identify new drug targets and develop novel antimicrobials. Metabolic homeostasis of bacteria plays an essential role in their virulence and resistance to antibiotics. Recent studies demonstrated that antibiotic efficacies can be improved by modulating the bacterial metabolism. Pseudomonas aeruginosa is an important opportunistic human pathogen that causes various infections. The bacterium is intrinsically resistant to antibiotics. In this study, we provide clear evidence that TpiA (triosephosphate isomerase) plays an essential role in the metabolism of P. aeruginosa and influences bacterial virulence and antibiotic resistance. The significance of this work is in identifying a key enzyme in the metabolic network, which will provide clues as to the development of novel treatment strategies against infections caused by P. aeruginosa.Yushan XiaDan WangXiaolei PanBin XiaYuding WengYuqing LongHuan RenJingyi ZhouYongxin JinFang BaiZhihui ChengShouguang JinWeihui WuAmerican Society for MicrobiologyarticlePseudomonas aeruginosaantibiotic resistancecarbon catabolite repressiontriosephosphate isomerasevirulenceMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pseudomonas aeruginosa antibiotic resistance carbon catabolite repression triosephosphate isomerase virulence Microbiology QR1-502
spellingShingle	Pseudomonas aeruginosa antibiotic resistance carbon catabolite repression triosephosphate isomerase virulence Microbiology QR1-502 Yushan Xia Dan Wang Xiaolei Pan Bin Xia Yuding Weng Yuqing Long Huan Ren Jingyi Zhou Yongxin Jin Fang Bai Zhihui Cheng Shouguang Jin Weihui Wu TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
description	ABSTRACT Carbon metabolism plays an essential role in bacterial pathogenesis and susceptibility to antibiotics. In Pseudomonas aeruginosa, Crc, Hfq, and a small RNA, CrcZ, are central regulators of carbon metabolism. By screening mutants of genes involved in carbon metabolism, we found that mutation of the tpiA gene reduces the expression of the type III secretion system (T3SS) and bacterial resistance to aminoglycoside antibiotics. TpiA is a triosephosphate isomerase that reversibly converts glyceraldehyde 3-phosphate to dihydroxyacetone phosphate, a key step connecting glucose metabolism with glycerol and phospholipid metabolisms. We found that mutation of the tpiA gene enhances the bacterial carbon metabolism, respiration, and oxidative phosphorylation, which increases the membrane potential and promotes the uptake of aminoglycoside antibiotics. Further studies revealed that the level of CrcZ is increased in the tpiA mutant due to enhanced stability. Mutation of the crcZ gene in the tpiA mutant background restored the expression of the T3SS genes and the bacterial resistance to aminoglycoside antibiotics. Overall, this study reveals an essential role of TpiA in the metabolism, virulence, and antibiotic resistance in P. aeruginosa. IMPORTANCE The increase in bacterial resistance against antibiotics imposes a severe threat to public health. It is urgent to identify new drug targets and develop novel antimicrobials. Metabolic homeostasis of bacteria plays an essential role in their virulence and resistance to antibiotics. Recent studies demonstrated that antibiotic efficacies can be improved by modulating the bacterial metabolism. Pseudomonas aeruginosa is an important opportunistic human pathogen that causes various infections. The bacterium is intrinsically resistant to antibiotics. In this study, we provide clear evidence that TpiA (triosephosphate isomerase) plays an essential role in the metabolism of P. aeruginosa and influences bacterial virulence and antibiotic resistance. The significance of this work is in identifying a key enzyme in the metabolic network, which will provide clues as to the development of novel treatment strategies against infections caused by P. aeruginosa.
format	article
author	Yushan Xia Dan Wang Xiaolei Pan Bin Xia Yuding Weng Yuqing Long Huan Ren Jingyi Zhou Yongxin Jin Fang Bai Zhihui Cheng Shouguang Jin Weihui Wu
author_facet	Yushan Xia Dan Wang Xiaolei Pan Bin Xia Yuding Weng Yuqing Long Huan Ren Jingyi Zhou Yongxin Jin Fang Bai Zhihui Cheng Shouguang Jin Weihui Wu
author_sort	Yushan Xia
title	TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_short	TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_full	TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_fullStr	TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_full_unstemmed	TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_sort	tpia is a key metabolic enzyme that affects virulence and resistance to aminoglycoside antibiotics through crcz in <named-content content-type="genus-species">pseudomonas aeruginosa</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/cbf728bb86554fda9f6bb29830423dfc
work_keys_str_mv	AT yushanxia tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT danwang tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT xiaoleipan tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT binxia tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT yudingweng tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT yuqinglong tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT huanren tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT jingyizhou tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT yongxinjin tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT fangbai tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT zhihuicheng tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT shouguangjin tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT weihuiwu tpiaisakeymetabolicenzymethataffectsvirulenceandresistancetoaminoglycosideantibioticsthroughcrczinnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent
_version_	1718427120263233536

TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>

Ejemplares similares