Functional Characterization of Plasmid-Borne rmpADC Homologues in Klebsiella pneumoniae
ABSTRACT Expression of the hypermucoviscosity (HMV) phenotype and capsular polysaccharide (CPS) biosynthesis in Klebsiella pneumoniae were reported to be encoded by genes located in the chromosomal rmp locus. However, the functions of the rmp locus in the virulence plasmid remained unclear, and most...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-06-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.03081-22 |
| _version_ | 1797803472502915072 |
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| author | Xuemei Yang Xiaoxuan Liu Edward Wai-Chi Chan Rong Zhang Sheng Chen |
| author_facet | Xuemei Yang Xiaoxuan Liu Edward Wai-Chi Chan Rong Zhang Sheng Chen |
| author_sort | Xuemei Yang |
| collection | DOAJ |
| description | ABSTRACT Expression of the hypermucoviscosity (HMV) phenotype and capsular polysaccharide (CPS) biosynthesis in Klebsiella pneumoniae were reported to be encoded by genes located in the chromosomal rmp locus. However, the functions of the rmp locus in the virulence plasmid remained unclear, and most of the rmp loci in clinical K. pneumoniae are plasmid carried. In this study, we investigated the functional characteristics of plasmid-borne rmp homologues in clinical hypervirulent K. pneumoniae (hvKP) strains by cloning and introducing such gene homologues into K. pneumoniae strains of different capsule types, followed by the evaluation of phenotypic changes in these strains. Acquisition of the plasmid-borne prmpADC and prmpA2D2 loci were found to result in an increase in mucoviscosity and CPS production in K1 and K2 K. pneumoniae, while only the prmpA2D2 locus contributed to phenotypic changes in the ST11/KL64 strain. Consistently, both rmpD and rmpD2 increased HMV in K1 and K2 K. pneumoniae, while only rmpD2 contributed to HMV in the ST11/KL64 strain; rmpC contributed to CPS overproduction in K1 and K2 strains but not in the ST11/KL64 strain. Furthermore, we proposed a logistic molecular basis of the HMV phenotype of K. pneumoniae on which prmpD2-mediated HMV is attributed to the increase of cell-free CPS production. Our data confirm that the rmp homologues carried by the virulence plasmid play a key role in virulence expression in K. pneumoniae, but the phenotype is highly dependent on the genetic background of the host strain and explained why most of the clinical ST11 strains carry only the prmpA2D2 locus. IMPORTANCE Klebsiella pneumoniae has become the most frequently isolated bacterial pathogen in hospital settings, with a very high mortality rate worldwide. Factors contributing to the virulence of K. pneumoniae are the overproduction of capsular polysaccharide (CPS) as well as the hypermucoviscosity (HMV) phenotype. These two phenotypes were reported to be regulated by rmpA/A2 homologues, which are often carried by virulence plasmids. Here, we determined the functional role of two plasmid-borne rmpA in mediating expression of the HMV phenotype and CPS production in K. pneumoniae. Different capsule types exhibited differences in the expression of HMV and CPS production although they harbored an identical plasmid-borne rmpA or rmpA2 locus, indicating that these virulence-related phenotypes are strongly related to the genetic background of the host strains. Our study provides a novel understanding of the regulation of virulence-related phenotypes and clinical management of K. pneumoniae infections. |
| first_indexed | 2024-03-13T05:21:27Z |
| format | Article |
| id | doaj.art-827406b47686444dbbbefafc57f8d82f |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-13T05:21:27Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-827406b47686444dbbbefafc57f8d82f2023-06-15T13:18:30ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.03081-22Functional Characterization of Plasmid-Borne rmpADC Homologues in Klebsiella pneumoniaeXuemei Yang0Xiaoxuan Liu1Edward Wai-Chi Chan2Rong Zhang3Sheng Chen4Department of Food Science and Nutrition, Faculty of Science, The Hong Kong Polytechnic University, Hung Hom, Hong KongDepartment of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong KongState Key Lab of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong KongDepartment of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Food Science and Nutrition, Faculty of Science, The Hong Kong Polytechnic University, Hung Hom, Hong KongABSTRACT Expression of the hypermucoviscosity (HMV) phenotype and capsular polysaccharide (CPS) biosynthesis in Klebsiella pneumoniae were reported to be encoded by genes located in the chromosomal rmp locus. However, the functions of the rmp locus in the virulence plasmid remained unclear, and most of the rmp loci in clinical K. pneumoniae are plasmid carried. In this study, we investigated the functional characteristics of plasmid-borne rmp homologues in clinical hypervirulent K. pneumoniae (hvKP) strains by cloning and introducing such gene homologues into K. pneumoniae strains of different capsule types, followed by the evaluation of phenotypic changes in these strains. Acquisition of the plasmid-borne prmpADC and prmpA2D2 loci were found to result in an increase in mucoviscosity and CPS production in K1 and K2 K. pneumoniae, while only the prmpA2D2 locus contributed to phenotypic changes in the ST11/KL64 strain. Consistently, both rmpD and rmpD2 increased HMV in K1 and K2 K. pneumoniae, while only rmpD2 contributed to HMV in the ST11/KL64 strain; rmpC contributed to CPS overproduction in K1 and K2 strains but not in the ST11/KL64 strain. Furthermore, we proposed a logistic molecular basis of the HMV phenotype of K. pneumoniae on which prmpD2-mediated HMV is attributed to the increase of cell-free CPS production. Our data confirm that the rmp homologues carried by the virulence plasmid play a key role in virulence expression in K. pneumoniae, but the phenotype is highly dependent on the genetic background of the host strain and explained why most of the clinical ST11 strains carry only the prmpA2D2 locus. IMPORTANCE Klebsiella pneumoniae has become the most frequently isolated bacterial pathogen in hospital settings, with a very high mortality rate worldwide. Factors contributing to the virulence of K. pneumoniae are the overproduction of capsular polysaccharide (CPS) as well as the hypermucoviscosity (HMV) phenotype. These two phenotypes were reported to be regulated by rmpA/A2 homologues, which are often carried by virulence plasmids. Here, we determined the functional role of two plasmid-borne rmpA in mediating expression of the HMV phenotype and CPS production in K. pneumoniae. Different capsule types exhibited differences in the expression of HMV and CPS production although they harbored an identical plasmid-borne rmpA or rmpA2 locus, indicating that these virulence-related phenotypes are strongly related to the genetic background of the host strains. Our study provides a novel understanding of the regulation of virulence-related phenotypes and clinical management of K. pneumoniae infections.https://journals.asm.org/doi/10.1128/spectrum.03081-22Klebsiella pneumoniaermpADC homologuesvirulence plasmidcapsulehypermucoviscosity |
| spellingShingle | Xuemei Yang Xiaoxuan Liu Edward Wai-Chi Chan Rong Zhang Sheng Chen Functional Characterization of Plasmid-Borne rmpADC Homologues in Klebsiella pneumoniae Microbiology Spectrum Klebsiella pneumoniae rmpADC homologues virulence plasmid capsule hypermucoviscosity |
| title | Functional Characterization of Plasmid-Borne rmpADC Homologues in Klebsiella pneumoniae |
| title_full | Functional Characterization of Plasmid-Borne rmpADC Homologues in Klebsiella pneumoniae |
| title_fullStr | Functional Characterization of Plasmid-Borne rmpADC Homologues in Klebsiella pneumoniae |
| title_full_unstemmed | Functional Characterization of Plasmid-Borne rmpADC Homologues in Klebsiella pneumoniae |
| title_short | Functional Characterization of Plasmid-Borne rmpADC Homologues in Klebsiella pneumoniae |
| title_sort | functional characterization of plasmid borne rmpadc homologues in klebsiella pneumoniae |
| topic | Klebsiella pneumoniae rmpADC homologues virulence plasmid capsule hypermucoviscosity |
| url | https://journals.asm.org/doi/10.1128/spectrum.03081-22 |
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