title: Low prevalence of rmpA and high tendency of rmpA mutation correspond to low virulence of extended spectrum β-lactamase-producing Klebsiella pneumoniae isolates.
abstract: Invasive syndrome caused by Klebsiella pneumoniae (KP), including liver abscess, is mainly caused by community-acquired strains with characteristics of positive hypermucoviscosity (HV) phenotype and regulator of mucoid phenotype A (rmpA) and transcriptional activator (rmpA2) genes. Extended- spectrum β-lactamase-producing KP (ESBL-KP) is commonly nosocomial and rarely HV-positive. We aimed to explore the reasons of the rarer prevalence of HV phenotype, rmpA and rmpA2 as well as the virulence phenotype among the ESBL-KP isolates from clinical specimens than those non-ESBL isolates. The β-lactamase genes, rmpA, rmpA2 and genes for K capsule serotype of 440 KP isolates were analyzed. The virulence of the isolates was characterized by the mouse lethality experiments. The prevalence rates of HV phenotype (∼ 50% vs. < 10%) as well as rmpA and rmpA2 genes (∼ 50-60% vs. < 20-30%) were significantly higher in non-ESBL group than in the ESBL group (p < 0.0001). Expression of HV phenotype in the rmpA-positive KP isolates was significantly rarer in the ESBL group than in non-ESBL group (33.3% vs. 91.9%, p < 0.0001). The frameshift mutations of rmpA and/or rmpA2 corresponded to negative HV phenotype of KP isolates that harbored the rmpA and/or rmpA2, resulting in variable mouse lethality (LD50, ∼ 10(3) - >5 × 10(7) CFU). The mutation rates might significantly differ among KP isolates from various sources. Virulence was dependent on rmpA-related HV phenotype. In conclusion, ESBL-KP isolates were less hypermucoviscous and less virulent than non-ESBL KP isolates, mostly due to concurrently lower carriage and higher mutation rates of the rmpA and rmpA2 genes.
authors.affiliation: a Department of Intensive Care Medicine ; Chi Mei Medical Center ; Tainan City , Taiwan.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Yu
authors.forename: Mei-Feng
authors.initials: MF
authors.lastname: Lee
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Tang
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Chang
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chuang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D016368:Frameshift Mutation; D005798:Genes, Bacterial; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D007928:Lethal Dose 50; D051379:Mice; D010641:Phenotype; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C512267:RmpA protein, Klebsiella pneumoniae; C082298:RmpA2 protein, Klebsiella pneumoniae; D014157:Transcription Factors; D001618:beta-Lactamases
keywords: ESBL hypermucoviscosity; klebsiella pneumoniae; rmpA gene; spontaneous mutation
references.citation: Int J Infect Dis. 2010 Aug;14(8):e688-92
references.pmid: 20547084
references.citation: J Bacteriol. 2010 Jun;192(12):3144-58
references.pmid: 20382770
references.citation: J Microbiol Immunol Infect. 2010 Feb;43(1):26-34
references.pmid: 20434120
references.citation: J Infect Dis. 2010 Apr 15;201(8):1259-67
references.pmid: 19785524
references.citation: Emerg Infect Dis. 2009 May;15(5):827-9
references.pmid: 19402984
references.citation: J Microbiol Immunol Infect. 2008 Aug;41(4):311-7
references.pmid: 18787738
references.citation: Diagn Microbiol Infect Dis. 2008 Sep;62(1):1-6
references.pmid: 18486404
references.citation: Emerg Infect Dis. 2007 Jul;13(7):986-93
references.pmid: 18214169
references.citation: Clin Infect Dis. 2007 Aug 1;45(3):284-93
references.pmid: 17599305
references.citation: J Infect Dis. 2007 Apr 15;195(8):1235-6; author reply 1236
references.pmid: 17357063
references.citation: J Clin Microbiol. 2007 Feb;45(2):466-71
references.pmid: 17151209
references.citation: Clin Infect Dis. 2006 May 15;42(10):1351-8
references.pmid: 16619144
references.citation: Microb Drug Resist. 2006 Spring;12(1):12-5
references.pmid: 16584302
references.citation: J Infect Dis. 1993 Dec;168(6):1415-21
references.pmid: 7902383
references.citation: Infect Immun. 1993 Aug;61(8):3164-74
references.pmid: 8335346
references.citation: Diagn Microbiol Infect Dis. 2004 Jun;49(2):125-9
references.pmid: 15183862
references.citation: J Exp Med. 2004 Mar 1;199(5):697-705
references.pmid: 14993253
references.citation: J Bacteriol. 2003 Feb;185(3):788-800
references.pmid: 12533454
references.citation: J Food Prot. 2011 Apr;74(4):559-64
references.pmid: 21477469
references.citation: J Med Microbiol. 2014 Mar;63(Pt 3):421-6
references.pmid: 24403599
references.citation: Clin Infect Dis. 2014 Jan;58(2):225-32
references.pmid: 24099919
references.citation: Pathol Biol (Paris). 2013 Oct;61(5):209-16
references.pmid: 23218835
references.citation: Nucleic Acids Res. 2013 Jul;41(Web Server issue):W29-33
references.pmid: 23609542
references.citation: Clin Infect Dis. 2012 Oct;55(7):930-9
references.pmid: 22715175
references.citation: Microbiology. 2011 Dec;157(Pt 12):3446-57
references.pmid: 21964731
references.citation: Microb Drug Resist. 2011 Jun;17(2):267-73
references.pmid: 21388296