Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulation

IntroductionHypervirulent Klebsiella pneumoniae produce an increased amount of capsular substance and are associated with a hypermucoviscous phenotype. Capsule production is regulated by capsular regulatory genes and capsular gene cluster variations. In the present study, we focus on the effect of r...

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Main Authors: Weiwen Wang, Dongxing Tian, Dakang Hu, Wenjie Chen, Ying Zhou, Xiaofei Jiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2023.1108818/full
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author Weiwen Wang
Dongxing Tian
Dakang Hu
Wenjie Chen
Ying Zhou
Xiaofei Jiang
author_facet Weiwen Wang
Dongxing Tian
Dakang Hu
Wenjie Chen
Ying Zhou
Xiaofei Jiang
author_sort Weiwen Wang
collection DOAJ
description IntroductionHypervirulent Klebsiella pneumoniae produce an increased amount of capsular substance and are associated with a hypermucoviscous phenotype. Capsule production is regulated by capsular regulatory genes and capsular gene cluster variations. In the present study, we focus on the effect of rmpA and wcaJon capsule biosynthesis.MethodsPhylogenetic trees were constructed to analyze wcaJ and rmpA sequence diversity in different serotypes hypervirulent strains. Then mutant strains (K2044ΔwcaJ, K2044K1wcaJ, K2044K2wcaJand K2044K64wcaJ) were used to verify the effects of wcaJ and its diversity on capsule synthesis and strain virulence. Furthmore, the role of rmpA in capsular synthesis and its mechanisms were detected in K2044ΔrmpA strain.ResultsRmpA sequences are conversed in different serotypes. And rmpA promoted the production of hypercapsules by simultaneously acting on three promoters in cps cluster. Whereas wcaJ, its sequences are different in different serotypes, and its loss result in the termination of capsular synthesis. Moreover, the results verified that K2 wcaJ could form hypercapsule in K2044 strains (K1 serotype), but K64 wcaJ could not.DiscussionThe interaction of multiple factors is involved in capsule synthesis, including wcaJ and rmpA. RmpA, an known conserved capsular regulator gene, acts on cps cluster promoters to promote the production of the hypercapsule. WcaJ as initiating enzyme of CPS biosynthesis, its presence determines the synthesis of capsule. Besides, different from rmpA, wcaJ sequence consistency is limited to the same serotype, which cause wcaJ functioning in different serotype strains with sequence recognition specificity.
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spelling doaj.art-20313fcb1eda4b01ab0b543929e0212c2023-04-25T05:05:47ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-04-011310.3389/fcimb.2023.11088181108818Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulationWeiwen Wang0Dongxing Tian1Dakang Hu2Wenjie Chen3Ying Zhou4Xiaofei Jiang5Department of Clinical Laboratory, Huashan Hospital of Fudan University, Shanghai, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining, ChinaDepartment of Laboratory Medicine, Taizhou Municipal Hospital, Taizhou, ChinaDepartment of Infectious Disease, Huashan Hospital of Fudan University, Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Pulmonary Hospital of Tongji University, Shanghai, ChinaDepartment of Clinical Laboratory, Huashan Hospital of Fudan University, Shanghai, ChinaIntroductionHypervirulent Klebsiella pneumoniae produce an increased amount of capsular substance and are associated with a hypermucoviscous phenotype. Capsule production is regulated by capsular regulatory genes and capsular gene cluster variations. In the present study, we focus on the effect of rmpA and wcaJon capsule biosynthesis.MethodsPhylogenetic trees were constructed to analyze wcaJ and rmpA sequence diversity in different serotypes hypervirulent strains. Then mutant strains (K2044ΔwcaJ, K2044K1wcaJ, K2044K2wcaJand K2044K64wcaJ) were used to verify the effects of wcaJ and its diversity on capsule synthesis and strain virulence. Furthmore, the role of rmpA in capsular synthesis and its mechanisms were detected in K2044ΔrmpA strain.ResultsRmpA sequences are conversed in different serotypes. And rmpA promoted the production of hypercapsules by simultaneously acting on three promoters in cps cluster. Whereas wcaJ, its sequences are different in different serotypes, and its loss result in the termination of capsular synthesis. Moreover, the results verified that K2 wcaJ could form hypercapsule in K2044 strains (K1 serotype), but K64 wcaJ could not.DiscussionThe interaction of multiple factors is involved in capsule synthesis, including wcaJ and rmpA. RmpA, an known conserved capsular regulator gene, acts on cps cluster promoters to promote the production of the hypercapsule. WcaJ as initiating enzyme of CPS biosynthesis, its presence determines the synthesis of capsule. Besides, different from rmpA, wcaJ sequence consistency is limited to the same serotype, which cause wcaJ functioning in different serotype strains with sequence recognition specificity.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1108818/fullcapsulewcaJrmpAVirulencehypervirulent Klebsiella pneumoniae
spellingShingle Weiwen Wang
Dongxing Tian
Dakang Hu
Wenjie Chen
Ying Zhou
Xiaofei Jiang
Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulation
Frontiers in Cellular and Infection Microbiology
capsule
wcaJ
rmpA
Virulence
hypervirulent Klebsiella pneumoniae
title Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulation
title_full Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulation
title_fullStr Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulation
title_full_unstemmed Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulation
title_short Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulation
title_sort different regulatory mechanisms of the capsule in hypervirulent klebsiella pneumonia direct wcaj variation vs indirect rmpa regulation
topic capsule
wcaJ
rmpA
Virulence
hypervirulent Klebsiella pneumoniae
url https://www.frontiersin.org/articles/10.3389/fcimb.2023.1108818/full
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