Abstract
Quantitative PCR (Q-PCR) is a fast and efficient tool to quantify target genes. In eukaryotic cells, quantitative reverse transcription-PCR (Q-RT-PCR) is also used to quantify gene expression, with stably expressed housekeeping genes as standards. In bacteria, such stable expression of housekeeping genes does not occur, and the use of DNA standards leads to a broad underestimation. Therefore, an accurate quantification of RNA is feasible only by using appropriate RNA standards. We established and validated a Q-PCR method which enables the quantification of not only the number of copies of target genes (i.e., the number of bacterial cells) but also the number of RNA copies. The genes coding for InvA and the 16S rRNA of Salmonella enterica serovar Typhimurium were selected for the evaluation of the method. As DNA standards, amplified fragments of the target genes were used, whereas the same DNA standards were transcribed in vitro for the development of appropriate RNA standards. Salmonella cultures and environmental water samples inoculated with bacteria were then employed for the final testing. Both experimental approaches led to a sensitive, accurate, and reproducible quantification of the selected target genes and RNA molecules by Q-PCR and Q-RT-PCR. It is the first time that RNA standards have been successfully used for a precise quantification of the number of RNA molecules in prokaryotes. This demonstrates the potential of this approach for determining the presence and metabolic activity of pathogenic bacteria in environmental samples.
MeSH Terms
Bacterial Proteins/genetics
Colony Count, Microbial
DNA Primers
DNA, Bacterial/genetics,standards
Environmental Monitoring/methods
Fresh Water/microbiology
Humans
Polymerase Chain Reaction/methods,standards
RNA, Bacterial/genetics,standards
RNA, Ribosomal, 16S/genetics
Salmonella typhimurium/isolation & purification
Sensitivity and Specificity
Chemicals
Bacterial Proteins
DNA Primers
DNA, Bacterial
RNA, Bacterial
RNA, Ribosomal, 16S
invA protein, Bacteria
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fey Axel
Division of Microbiology, GBF-German Research Center for Biotechnology, Braunschweig, Germany.
Eichler Stefan
Flavier Sébastien
Christen Richard
Höfle Manfred G
Guzmán Carlos A
References (23)
23 references, click to expand
-
Quantification of expression of Staphylococcus epidermidis housekeeping genes with Taqman quantitative PCR during in vitro growth and under different conditions.
J Bacteriol. 2001 Dec;183(24):7094-101
PMID: 11717267
-
Semi-automated fluorogenic PCR assays (TaqMan) forrapid detection of Escherichia coli O157:H7 and other shiga toxigenic E. coli.
Mol Cell Probes. 1999 Aug;13(4):291-302
PMID: 10441202
-
Simultaneous extraction from bacterioplankton of total RNA and DNA suitable for quantitative structure and function analyses.
Appl Environ Microbiol. 2002 Mar;68(3):1082-7
PMID: 11872453
-
Tech.Sight. A technique whose time has come.
Science. 2002 Apr 19;296(5567):557-9
PMID: 11964485
-
Persistent DNA contamination in competitive RT-PCR using cRNA internal standards: identity, quantity, and control.
Biotechniques. 2002 Jun;32(6):1412-4, 1416-7
PMID: 12074174
-
Real-time PCR quantification of rbcL (ribulose-1,5-bisphosphate carboxylase/oxygenase) mRNA in diatoms and pelagophytes.
Appl Environ Microbiol. 2002 Aug;68(8):3771-9
PMID: 12147471
-
A new mathematical model for relative quantification in real-time RT-PCR.
Nucleic Acids Res. 2001 May 1;29(9):e45
PMID: 11328886
-
Multicenter validation of the analytical accuracy of Salmonella PCR: towards an international standard.
Appl Environ Microbiol. 2003 Jan;69(1):290-6
PMID: 12514007
-
Molecular methods for the assessment of bacterial viability.
J Microbiol Methods. 2003 May;53(2):175-83
PMID: 12654489
-
Towards a unified system for detecting waterborne pathogens.
J Microbiol Methods. 2003 May;53(2):185-97
PMID: 12654490
-
A rapid and direct real time PCR-based method for identification of Salmonella spp.
J Microbiol Methods. 2003 Sep;54(3):381-90
PMID: 12842485
-
Quantification of dissimilatory (bi)sulphite reductase gene expression in Desulfobacterium autotrophicum using real-time RT-PCR.
Environ Microbiol. 2003 Aug;5(8):660-71
PMID: 12871233
-
Computational methods and evaluation of RNA stabilization reagents for genome-wide expression studies.
J Microbiol Methods. 2003 Nov;55(2):399-409
PMID: 14529961
-
rRNA transcription and growth rate-dependent regulation of ribosome synthesis in Escherichia coli.
Annu Rev Microbiol. 1996;50:645-77
PMID: 8905094
-
PCR detection, characterization, and distribution of virulence genes in Aeromonas spp.
Appl Environ Microbiol. 1999 Dec;65(12):5293-302
PMID: 10583979
-
Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays.
J Mol Endocrinol. 2000 Oct;25(2):169-93
PMID: 11013345
-
Assessment of Helicobacter pylori gene expression within mouse and human gastric mucosae by real-time reverse transcriptase PCR.
Infect Immun. 2001 Aug;69(8):4759-66
PMID: 11447148
-
Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.
Nature. 2001 Oct 25;413(6858):852-6
PMID: 11677609
-
Detection and characterization of Shiga toxigenic Escherichia coli by using multiplex PCR assays for stx1, stx2, eaeA, enterohemorrhagic E. coli hlyA, rfbO111, and rfbO157.
J Clin Microbiol. 1998 Feb;36(2):598-602
PMID: 9466788
-
Detection of mRNA by reverse transcription-PCR as an indicator of viability in Escherichia coli cells.
Appl Environ Microbiol. 1998 Apr;64(4):1313-8
PMID: 9546166
-
Differential priming of RNA templates during cDNA synthesis markedly affects both accuracy and reproducibility of quantitative competitive reverse-transcriptase PCR.
Biochem J. 1999 Jan 15;337 ( Pt 2):231-41
PMID: 9882620
-
Quantitative RT-PCR: pitfalls and potential.
Biotechniques. 1999 Jan;26(1):112-22, 124-5
PMID: 9894600
-
Use of gDNA as internal standard for gene expression in staphylococci in vitro and in vivo.
Biochem Biophys Res Commun. 2002 Mar 1;291(3):528-34
PMID: 11855820