Hfq mutation confers increased cephalosporin resistance in Klebsiella pneumoniae

Authors

  • Xinran Li 1. College of Animal Sciences, Jilin University, Changchun; 2. Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agriculture University, Shenyang
  • Mingjuan Yang Department of Infectious Disease Control, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing
  • Yuehua Ke Department of Infectious Disease Control, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing
  • Mingyuan Liu Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun
  • Yufei Wang Department of laboratory medicine, the General Hospital of Chinese people’s Armed Police Forces, Beijing
  • Shiwei Liu Wangjing Hospital, Academy of Chinese Traditional Medicine, Beijing
  • Bo Liu 1. Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun; 2. Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun
  • Zeliang Chen 1. Department of Infectious Disease Control, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Changchun; 2. Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agriculture University, Changchun

Keywords:

Cephalosporins, hfq, Klebsiella pneumoniae, penicillin-binding proteins, resistance

Abstract

Klebsiella pneumoniae (K. pneumoniae), is an opportunistic pathogen raising significant public health concerns owing to its multi-drug resistance. Hfq, one of the main RNA-binding proteins, is a key post-transcriptional regulator. This protein is closely related to virulence and resistance in various pathogenic bacteria. Although the role of hfq in K. pneumoniae virulence has been explored, its influence on resistance remains largely unknown. The aim of this study was to investigate the role of hfq in the resistance of K. pneumoniae to cephalosporins. An hfq mutant was constructed, and its resistance to cephalosporins was investigated. The hfq mutant exhibited over 16-fold higher cephalosporin resistance than that exhibited by the wild type. Time-kill curve analysis showed that the hfq mutant could survive under higher concentrations of cephalosporins than the wild-type strain could. Quantitative RT-PCR showed that expression levels for 8 out of the 9 penicillin-binding proteins, which are the targets of cephalosporins, were downregulated in the hfq mutant. Taken together, contrary to its role in many other bacteria, hfq is involved in a negative regulation of K. pneumoniae resistance to cephalosporins by downregulating the expression of penicillin-binding proteins.

DOI: 10.2298/ABS160126078L

Received: January 26, 2016; Revised: March 20, 2016; Accepted: April 30, 2016; Published online: September 14, 2016

How to cite this article: Li X, Yang M, Ke Y, Liu M, Wang Y, Liu S, Liu B, Chen Z. Hfq mutation confers increased cephalosporin resistance in Klebsiella pneumoniae. Arch Biol Sci. 2017;69(1):61-9.

Downloads

Download data is not yet available.

References

Banapurmath CR, Kallinath S, Banapurmath S, Kalliath A, Kesaree N. Congenital pneumonia caused by Klebsiella pneumoniae. Indian Pediatr. 1994;31(10):1264-6.

Kil KS, Darouiche RO, Hull RA, Mansouri MD, Musher DM. Identification of a Klebsiella pneumoniae strain associated with nosocomial urinary tract infection. J Clin Microbiol. 1997;35(9):2370-4.

Soscia JL, Dibenedetto R, Crocco J. Klebsiella pneumoniae meningitis. Report of a Case and Review of the Literature. Arch Intern Med. 1964;113:569-72.

Huck RF. Cholecystitis, septicemia, and cystitis due to Klebsiella pneumoniae. U S Armed Forces Med J. 1956;7(9):1368-72.

Casanova C, Lorente JA, Carrillo F, Perez-Rodriguez E, Nunez N. Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. Arch Intern Med. 1989;149(6):1467.

World Health Organization. Antimicrobial Resistance: Global Report on Surveillance. 2014. Geneva, Switzerland: World Health Organization; 2014. [cited 6 December 2015]. 232 p. Available from: http://www.who.int/drugresistance/documents/surveillancereport/en/.

Sonnleitner E, Hagens S, Rosenau F, Wilhelm S, Habel A, Jager KE, Blasi, U. Reduced virulence of a hfq mutant of Pseudomonas aeruginosa O1. Microb Pathog. 2003;35(5):217-28.

Christiansen JK, Larsen MH, Ingmer H, Sogaard-Andersen L, Kallipolitis BH. The RNA-binding protein Hfq of Listeria monocytogenes: role in stress tolerance and virulence. J Bacteriol. 2004;186(11):3355-62.

Ding Y, Davis BM, Waldor MK. Hfq is essential for Vibrio cholerae virulence and downregulates sigma expression. Mol Microbiol. 2004;53(1):345-54.

Sharma AK, Payne SM. Induction of expression of hfq by DksA is essential for Shigella flexneri virulence. Mol Microbiol. 2006;62(2):469-79.

Sittka A, Pfeiffer V, Tedin K, Vogel J. The RNA chaperone Hfq is essential for the virulence of Salmonella typhimurium. Mol Microbiol. 2007;63(1):193-217.

Ansong C, Yoon H, Porwollik S, Mottaz-Brewer H, Petritis BO, Jaitly N, Adkins JN, McClelland M, Heffron F, Smith RD. Global systems-level analysis of Hfq and SmpB deletion mutants in Salmonella: implications for virulence and global protein translation. PLoS One. 2009;4(3):e4809.

Dietrich M, Munke R, Gottschald M, Ziska E, Boettcher JP, Mollenkopf H, Friedrich A. The effect of hfq on global gene expression and virulence in Neisseria gonorrhoeae. FEBS J. 2009;276(19):5507-20.

Fantappie L, Metruccio MM, Seib KL, Oriente F, Cartocci E, Ferlicca F, Giuliani MM, Scarlato V, Delany I. The RNA chaperone Hfq is involved in stress response and virulence in Neisseria meningitidis and is a pleiotropic regulator of protein expression. Infect Immun. 2009;77(5):1842-53.

Geng J, Song Y, Yang L, Feng Y, Qiu Y, Li G, Guo J, Bi Y, Qu Y, Wang W, Wang X, Guo Z, Yang R, Han Y. Involvement of the post-transcriptional regulator Hfq in Yersinia pestis virulence. PLoS One. 2009;4(7):e6213.

Schiano CA, Bellows LE, Lathem WW. The small RNA chaperone Hfq is required for the virulence of Yersinia pseudotuberculosis. Infect Immun. 2010;78(5):2034-44.

Meibom KL, Forslund AL, Kuoppa K, Alkhuder K, Dubail I, Dupuis M, Forsberg A, Charbit A. Hfq, a novel pleiotropic regulator of virulence-associated genes in Francisella tularensis. Infect Immun. 2009;77(5):1866-80.

Zeng Q, McNally RR, Sundin GW. Global small RNA chaperone Hfq and regulatory small RNAs are important virulence regulators in Erwinia amylovora. J Bacteriol. 2013;195(8):1706-17.

Kendall MM, Gruber CC, Rasko DA, Hughes DT, Sperandio V. Hfq virulence regulation in enterohemorrhagic Escherichia coli O157:H7 strain 86-24. J Bacteriol. 2011;193(24):6843-51.

Simonsen KT, Nielsen G, Bjerrum JV, Kruse T, Kallipolitis BH, Moller-Jensen J. A role for the RNA chaperone Hfq in controlling adherent-invasive Escherichia coli colonization and virulence. PLoS One. 2011;6(1):e16387.

Chao Y, Vogel J. The role of Hfq in bacterial pathogens. Curr Opin Microbiol. 2010;13(1):24-33.

Van Assche E, Van Puyvelde S, Vanderleyden J, Steenackers HP. RNA-binding proteins involved in post-transcriptional regulation in bacteria. Front Microbiol. 2015;6:141.

Faner MA, Feig AL. Identifying and characterizing Hfq-RNA interactions. Methods. 2013;63(2):144-59.

Vogel J, Luisi BF. Hfq and its constellation of RNA. Nat Rev Microbiol. 2011;9(8):578-89.

Chiang MK, Lu MC, Liu LC, Lin CT, Lai YC. Impact of Hfq on global gene expression and virulence in Klebsiella pneumoniae. PLoS One. 2011;6(7):e22248.

Kalant H. The pharmacology of semisynthetic antibiotics. Can Med Assoc J. 1965;93(16):839-43.

Livermore DM. Mechanisms of resistance to cephalosporin antibiotics. Drugs. 1987;34(Suppl.2):64-88.

Torok ME, Chantratita N, Peacock SJ. Bacterial gene loss as a mechanism for gain of antimicrobial resistance. Curr Opin Microbiol. 2012;15(5):583-7.

Krauss J, Hakenbeck R. A mutation in the D,D-carboxypeptidase penicillin-binding protein 3 of Streptococcus pneumoniae contributes to cefotaxime resistance of the laboratory mutant C604. Antimicrob Agents Chemother. 1997;41(5):936-42.

Chantratita N, Rholl DA, Sim B, Wuthiekanun V, Limmathurotsakul D, Amornchai P, Thanwisai A, Chua HH, Ooi WF, Holden MT, Day NP, Tan P, Schweizer HP, Peacock SJ. Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei. Proc Natl Acad Sci U S A. 2011;108(41):17165-70.

Wei D, Wang M, Shi J, Hao J. Red recombinase assisted gene replacement in Klebsiella pneumoniae. J Ind Microbiol Biotechnol. 2012;39(8):1219-26.

Doublet B, Douard G, Targant H, Meunier D, Madec JY, Cloeckaert A. Antibiotic marker modifications of lambda Red and FLP helper plasmids, pKD46 and pCP20, for inactivation of chromosomal genes using PCR products in multidrug-resistant strains. J Microbiol Methods. 2008;75(2):359-61.

Jayol A, Poirel L, Brink A, Villegas MV, Yilmaz M, Nordmann P. Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide origin. Antimicrob Agents Chemother. 2014;58(8):4762-6.

Srinivasan VB, Rajamohan G. KpnEF, a new member of the Klebsiella pneumoniae cell envelope stress response regulon, is an SMR-type efflux pump involved in broad-spectrum antimicrobial resistance. Antimicrob Agents Chemother. 2013;57(9):4449-62.

Moya B, Dotsch A, Juan C, Blazquez J, Zamorano L, Haussler S, Oliver A. Beta-lactam resistance response triggered by inactivation of a nonessential penicillin-binding protein. PLoS Pathog. 2009;5(3):e1000353.

Vashist J, Tiwari V, Das R, Kapil A, Rajeswari MR. Analysis of penicillin-binding proteins (PBPs) in carbapenem resistant Acinetobacter baumannii. Indian J Med Res. 2011;133:332-8.

Mottl H, Nieland P, de Kort G, Wierenga JJ, Keck W. Deletion of an additional domain located between SXXK and SXN active-site fingerprints in penicillin-binding protein 4 from Escherichia coli. J Bacteriol. 1992;174(10):3261-9.

Sanders CC, Bradford PA, Ehrhardt AF, Bush K, Young KD, Henderson TA, Sanders WE Jr. Penicillin-binding proteins and induction of AmpC beta-lactamase. Antimicrob Agents Chemother. 1997;41(9):2013-5.

Downloads

Published

2017-03-07

How to Cite

1.
Li X, Yang M, Ke Y, Liu M, Wang Y, Liu S, Liu B, Chen Z. Hfq mutation confers increased cephalosporin resistance in Klebsiella pneumoniae. Arch Biol Sci [Internet]. 2017Mar.7 [cited 2024Nov.21];69(1):61-9. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/78

Issue

Vol. 69 No. 1 (2017)

Section

Articles

License

Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.

Most read articles by the same author(s)