Altered metabolic pathways in classic and hypervirulent Klebsiella pneumoniae isolates revealed by proteomics analysis

Authors

  • Hui Yu 1. School of Basic Medicine, Baotou Medical College, Baotou 014060, China; 2. Inner Mongolia Key Laboratory of Disease-Related Biomarkers, Baotou Medical College, Baotou 014060, China
  • Lixia Zhang The First Affiliated Hospital, Baotou Medical College, Baotou 014010, China
  • Rina Su The Second Affiliated Hospital, Baotou Medical College, Baotou 014030, China
  • Hai Hu School of Basic Medicine, Baotou Medical College, Baotou 014060, China
  • Zhanli Wang Inner Mongolia Key Laboratory of Disease-Related Biomarkers, Baotou Medical College, Baotou 014060, China

DOI:

https://doi.org/10.2298/ABS220613022Y

Keywords:

Klebsiella pneumoniae, Virulence, Proteomics, Metabolic pathway

Abstract

Paper description:

  • Differences between the virulence and pathogenic characteristics of hypervirulent Klebsiella pneumoniae and classical pneumoniae are poorly understood.
  • Using comparative proteomics we explored the correlation between the expression characteristics of proteins and hypervirulence.
  • Of 451 significantly differentially expressed proteins, 185 were significantly upregulated and 266 were significantly downregulated. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the differentially expressed proteins were predominantly metabolism associated.
  • Our results contribute to a better understanding of the virulence and pathogenic characteristics of hypervirulent pneumoniae.

Abstract: Klebsiella pneumoniae is an opportunistic pathogen that causes a wide range of infections. The emergence and spread of hypervirulent K. pneumoniae (hvKp), which appears to be different from the classical K. pneumoniae (cKp) in several microbiological aspects, is an urgent global threat. However, the virulence characteristics of hvKp and its differences from cKp are poorly understood. This work aimed to investigate the correlation between the expression characteristics of proteins and hypervirulence, using proteomics. Our results revealed that 185 proteins were upregulated while 266 proteins were downregulated in hvKp isolates when compared with cKp isolates. The differentially expressed proteins were functionally categorized according to the Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. These proteins were predominantly metabolism associated, which indicates that changes in the metabolic pathways in hvKp isolates might in part contribute to hypervirulence.

Downloads

Download data is not yet available.

References

Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev. 1998;11:589-603. https://doi.org/10.1128/CMR.11.4.589

Paczosa MK, Mecsas J. Klebsiella pneumoniae: going on the offense with a strong defense. Microbiol Mol Biol Rev. 2016;80:629-61. https://doi.org/10.1128/MMBR.00078-15

Chew KL, Lin RTP, Teo JWP. Klebsiella pneumoniae in Singapore: hypervirulent infections and the carbapenemase threat. Front Cell Infect Microbiol. 2017;7:515. https://doi.org/10.3389/fcimb.2017.00515

Russo TA, Marr CM. Hypervirulent Klebsiella pneumoniae. Clin Microbiol Rev. 2019;32:e00001-19. https://doi.org/10.1128/CMR.00001-19

Siu LK, Yeh KM, Lin JC, Fung CP, Chang FY. Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis. 2012;12:881-7. https://doi.org/10.1016/S1473-3099(12)70205-0

Lee IR, Molton JS, Wyres KL, Gorrie C, Wong J, Hoh CH, Teo J, Kalimuddin S, Lye DC, Archuleta S, Holt KE, Gan YH. Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population. Sci Rep. 2016;6:29316. https://doi.org/10.1038/srep29316

Prokesch BC, TeKippe M, Kim J, Raj P, TeKippe EM, Greenberg DE. Primary osteomyelitis caused by hypervirulent Klebsiella pneumoniae. Lancet Infect Dis. 2016;16:e190-5. https://doi.org/10.1016/S1473-3099(16)30021-4

Behera P, Nikhil KC, Kumar A, Gali JM, De A, Mohanty AK, Ali MA, Sharma B. Comparative proteomic analysis of Salmonella Typhimurium wild type and its isogenic fnr null mutant during anaerobiosis reveals new insight into bacterial metabolism and virulence. Microb Pathog. 2020;140:103936. https://doi.org/10.1016/j.micpath.2019.103936

Rico-San Román L, Horcajo P, Regidor-Cerrillo J, Fernández-Escobar M, Collantes-Fernández E, Gutiérrez-Blázquez D, Hernáez-Sánchez ML, Saeij JPJ, Ortega-Mora LM. Comparative tachyzoite proteome analyses among six Neospora caninum isolates with different virulence. Int J Parasitol. 2020;50:377-88. https://doi.org/10.1016/j.ijpara.2020.02.003

Zhang M, Zhang J, Li J, Wu X, Xiao L, Liu X, Yang X, Yang L, Zou Q, Huang W. AmpR increases the virulence of carbapenem-resistant Klebsiella pneumoniae by regulating the initial step of capsule synthesis. Infect Drug Resist. 2020;13:3431-41. https://doi.org/10.2147/IDR.S269275

Sukumaran A, Pladwig S, Geddes-McAlister J. Zinc limitation in Klebsiella pneumoniae profiled by quantitative proteomics influences transcriptional regulation and cation transporter-associated capsule production. BMC Microbiol. 2021;21:43. https://doi.org/10.1186/s12866-021-02091-8

Shi Y, Chen Y, Yang Z, Zhang Y, You B, Liu X, Chen P, Liu M, Zhang C, Luo X, Chen Y, Yuan Z, Chen J, Gong Y, Peng Y. Characterization and genome sequencing of a novel T7-like lytic phage, kpssk3, infecting carbapenem-resistant Klebsiella pneumoniae. Arch Virol. 2020;165:97-104. https://doi.org/10.1007/s00705-019-04447-y

Zafar S, Hanif S, Akhtar H, Faryal R. Emergence of hypervirulent K. pneumoniae causing complicated UTI in kidney stone patients. Microb Pathog. 2019;135:103647. https://doi.org/10.1016/j.micpath.2019.103647

Gehring T, Kim HJ, Dibloni E, Neuenhoff M, Buechler C. Comparison of antimicrobial susceptibility test results of disk diffusion, gradient strip, and automated dilution with broth microdilution for piperacillin-tazobactam. Microb Drug Resist. 2021;27:1305-11. https://doi.org/10.1089/mdr.2020.0011

Shen C, Shen Y, Zhang H, Xu M, He L, Qie J. Comparative proteomics demonstrates altered metabolism pathways in cotrimoxazole-resistant and amikacin-resistant Klebsiella pneumoniae isolates. Front Microbiol. 2021;12:773829. https://doi.org/10.3389/fmicb.2021.773829

Wang G, Zhao G, Chao X, Xie L, Wang H. The characteristic of virulence, biofilm and antibiotic resistance of Klebsiella pneumoniae. Int J Environ Res Public Health. 2020;17:6278. https://doi.org/10.3390/ijerph17176278

Yang G, Xu Q, Chen S. Neutrophil function in hypervirulent Klebsiella pneumoniae infection. Lancet Microbe. 2022;3:e248. https://doi.org/10.1016/S2666-5247(22)00004-0

Korkhov VM, Mireku SA, Hvorup RN, Locher KP. Asymmetric states of vitamin B₁₂ transporter BtuCD are not discriminated by its cognate substrate binding protein BtuF. FEBS Lett. 2012;586:972-6. https://doi.org/10.1016/j.febslet.2012.02.042

O'Flynn C, Deusch O, Darling AE, Eisen JA, Wallis C, Davis IJ, Harris SJ. Comparative genomics of the genus porphyromonas identifies adaptations for heme synthesis within the prevalent canine oral species Porphyromonas cangingivalis. Genome Biol Evol. 2015;7(129):3397-413. https://doi.org/10.1093/gbe/evv220

de Paiva JB, Penha Filho RA, Arguello YM, Berchieri Junior A, Lemos MV, Barrow PA. A defective mutant of Salmonella enterica Serovar Gallinarum in cobalamin biosynthesis is avirulent in chickens. Braz J Microbiol. 2009;40:495-504. https://doi.org/10.1590/S1517-83822009000300012

Sanders AN, Pavelka MS. Phenotypic analysis of Escherichia coli mutants lacking L,D-transpeptidases. Microbiology. 2013;159(Pt9):1842-52. https://doi.org/10.1099/mic.0.069211-0

Duda DM, Walden H, Sfondouris J, Schulman BA. Structural analysis of Escherichia coli ThiF. J Mol Biol. 2005;349:774- 86. https://doi.org/10.1016/j.jmb.2005.04.011

Xu Z, Wang Y, Han Y, Chen J, Zhang XH. Mutation of a novel virulence-related gene mltD in Vibrio anguillarum enhances lethality in zebra fish. Res Microbiol. 2011;162:144-50. https://doi.org/10.1016/j.resmic.2010.08.003

Bouillaut L, Dubois T, Sonenshein AL, Dupuy B. Integration of metabolism and virulence in Clostridium difficile. Res Microbiol. 2015;166(4):375-83. https://doi.org/10.1016/j.resmic.2014.10.002

Kitphati W, Ngok-Ngam P, Suwanmaneerat S, Sukchawalit R, Mongkolsuk S. Agrobacterium tumefaciens fur has important physiological roles in iron and manganese homeostasis, the oxidative stress response, and full virulence. Appl Environ Microbiol. 2007;73:4760-8. https://doi.org/10.1128/AEM.00531-07

Smith AT, Sestok AE. Expression and purification of functionally active ferrous iron transporter FeoB from Klebsiella pneumoniae. Protein Expr Purif. 2018;142:1-7. https://doi.org/10.1016/j.pep.2017.09.007

Sun WS, Syu WJ, Ho WL, Lin CN, Tsai SF, Wang SH. SitA contributes to the virulence of Klebsiella pneumoniae in a mouse infection model. Microbes Infect. 2014;16:161-70. https://doi.org/10.1016/j.micinf.2013.10.019

Gaballa A, Helmann JD. Bacillus subtilis Fur represses one of two paralogous haem-degrading monooxygenases. Microbiology. 2011;157(Pt11):3221-31. https://doi.org/10.1099/mic.0.053579-0

Hosfelt J, Richards A, Zheng M, Adura C, Nelson B, Yang A, Fay A, Resager W, Ueberheide B, Glickman JF, Lupoli TJ. An allosteric inhibitor of bacterial Hsp70 chaperone potentiates antibiotics and mitigates resistance. Cell Chem Biol. 2022;29:854-69.e9. https://doi.org/10.1016/j.chembiol.2021.11.004

Kallscheuer N, Gätgens J, Lübcke M, Pietruszka J, Bott M, Polen T. Improved production of adipate with Escherichia coli by reversal of β-oxidation. Appl Microbiol Biotechnol. 2017;101:2371-82. https://doi.org/10.1007/s00253-016-8033-3

Dong W, Nie X, Zhu H, Liu Q, Shi K, You L, Zhang Y, Fan H, Yan B, Niu C, Lyu LD, Zhao GP, Yang C. Mycobacterial fatty acid catabolism is repressed by FdmR to sustain lipogenesis and virulence. Proc Natl Acad Sci U S A. 2021;118:e2019305118. https://doi.org/10.1073/pnas.2019305118

Díaz-Pérez SP, Patiño-Medina JA, Valle-Maldonado MI, López-Torres A, Jácome-Galarza IE, Anaya-Martínez V, Gómez-Ruiz V, Campos-García J, Nuñez-Anita RE, Ortiz-Alvarado R, Ramírez-Díaz MI, Gutiérrez-Corona JF, Meza-Carmen V. Alteration of fermentative metabolism enhances Mucor circinelloides virulence. Infect Immun. 2020;88:e00434-19. https://doi.org/10.1128/IAI.00434-19

Downloads

Published

2022-10-05

How to Cite

1.
Yu H, Zhang L, Su R, Hu H, Wang Z. Altered metabolic pathways in classic and hypervirulent Klebsiella pneumoniae isolates revealed by proteomics analysis. Arch Biol Sci [Internet]. 2022Oct.5 [cited 2024Dec.25];74(3):235-42. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/7846

Issue

Section

Articles