Abstract
PCR-single-strand conformation polymorphism (PCR-SSCP) analysis is a rapid and convenient technique for the detection of mutations and allelic variants. We have adapted this technique for the identification of bacteria by PCR with fluorescein-labeled primers chosen from the conserved regions of the 16S rRNA gene flanking a variable region. The PCR product was denatured, separated on a nondenaturing gel, and detected by an automated DNA sequencer. The mobility of the single-stranded DNA is sequence dependent and allows the identification of a broad panel of bacteria. A single nucleotide difference in the amplified region was sufficient to obtain different PCR-SSCP patterns. The simultaneous amplification of multiple polymorphic regions by multiplex PCR with subsequent multiplex SSCP increased the discriminatory power of PCR-SSCP. A broad range of gram-negative and gram-positive bacteria were tested by PCR-SSCP, including, e.g., Escherichia coli, Enterobacter spp., Klebsiella spp., Haemophilus spp., Neisseria spp., Staphylococcus spp, Streptococcus spp., Enterococcus spp., and Bacillus spp. In total, a panel of 178 strains of bacteria representing 51 species in 21 genera was examined. Although a limited number of strains from each species were tested, the strains tested gave species-specific patterns, with only one exception: Shigella species were indistinguishable from E. coli. PCR is a sensitive technique; as few as 10 CFU of E. coli was sufficient to produce PCR-SSCP patterns suitable for identification. The whole fluorescence PCR-SSCP procedure takes approximately 8 h for the detection and identification of low numbers of bacteria.2+ fluorescence PCR-SSCP seems to be a promising method for the differentiation of a broad range of pathogens found in usually sterile clinical sites, such as blood and cerebrospinal fluid.
MeSH Terms
Bacteria/classification,genetics,pathogenicity
Base Sequence
Conserved Sequence
DNA Primers
DNA, Ribosomal/genetics
DNA-Directed DNA Polymerase/metabolism
Enzyme Stability
Fluorescence
Genes, Bacterial
Gram-Negative Bacteria/classification,genetics
Gram-Positive Bacteria/classification,genetics
Hot Temperature
Molecular Sequence Data
Polymerase Chain Reaction/methods
Polymorphism, Single-Stranded Conformational
RNA, Ribosomal, 16S/genetics
Chemicals
DNA Primers
DNA, Ribosomal
RNA, Ribosomal, 16S
DNA-Directed DNA Polymerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Widjojoatmodjo M N
p4p4man Winkler Institute for Medical and Clinical Microbiology, University Hospital Utrecht, The Netherlands.
Fluit A C
Verhoef J
References (20)
20 references, click to expand
-
Novel non-templated nucleotide addition reactions catalyzed by procaryotic and eucaryotic DNA polymerases.
Nucleic Acids Res. 1988 Oct 25;16(20):9677-86
PMID: 2460825
-
Rapid identification of bacteria by PCR-single-strand conformation polymorphism.
J Clin Microbiol. 1994 Dec;32(12):3002-7
PMID: 7883890
-
Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction.
Genomics. 1989 Nov;5(4):874-9
PMID: 2687159
-
Rapid determination of bacterial ribosomal RNA sequences by direct sequencing of enzymatically amplified DNA.
FEMS Microbiol Lett. 1989 Nov;53(1-2):171-6
PMID: 2482222
-
A general method to generate DNA probes for microorganisms.
Biotechnology (N Y). 1990 Mar;8(3):233-6
PMID: 1369980
-
Nucleotide sequence of Clostridium difficile toxin B gene.
Nucleic Acids Res. 1990 Jul 11;18(13):4004
PMID: 2374729
-
Amplification of bacterial 16S ribosomal DNA with polymerase chain reaction.
J Clin Microbiol. 1990 Sep;28(9):1942-6
PMID: 2095137
-
Diagnostic single strand conformational polymorphism, (SSCP): a simplified non-radioisotopic method as applied to a Tay-Sachs B1 variant.
Nucleic Acids Res. 1991 Jan 25;19(2):405-6
PMID: 2014179
-
Taq polymerase contains bacterial DNA of unknown origin.
Mol Cell Probes. 1990 Dec;4(6):445-50
PMID: 2087233
-
Phylogenetic analysis of the genus Listeria based on reverse transcriptase sequencing of 16S rRNA.
Int J Syst Bacteriol. 1991 Apr;41(2):240-6
PMID: 1713054
-
Magnesium-dependent thermostability of DNase I.
Biotechniques. 1992 Jul;13(1):64-6
PMID: 1503777
-
PCR-SSCP: a method for detection of mutations.
Genet Anal Tech Appl. 1992 Jun;9(3):73-9
PMID: 1476794
-
F-SSCP: fluorescence-based polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis.
PCR Methods Appl. 1992 Aug;2(1):10-3
PMID: 1490170
-
Elimination of contaminating DNA within polymerase chain reaction reagents: implications for a general approach to detection of uncultured pathogens.
J Clin Microbiol. 1993 Mar;31(3):646-52
PMID: 8458958
-
Rapid identification of bacteria on the basis of polymerase chain reaction-amplified ribosomal DNA spacer polymorphisms.
Appl Environ Microbiol. 1993 Apr;59(4):945-52
PMID: 8476298
-
Efficacy of fluorescence-based PCR-SSCP for detection of point mutations.
Biotechniques. 1993 Oct;15(4):684-91
PMID: 8251171
-
PCR primers and probes for the 16S rRNA gene of most species of pathogenic bacteria, including bacteria found in cerebrospinal fluid.
J Clin Microbiol. 1994 Feb;32(2):335-51
PMID: 7512093
-
Multiple fluorescence-based PCR-SSCP analysis.
Biotechniques. 1994 Feb;16(2):296-7, 300-5
PMID: 8179893
-
Polishing with T4 or Pfu polymerase increases the efficiency of cloning of PCR fragments.
Nucleic Acids Res. 1994 Jun 25;22(12):2423
PMID: 8036174
-
Broad range DNA probes for detecting and amplifying eubacterial nucleic acids.
FEMS Microbiol Lett. 1989 Jan 1;48(1):19-24
PMID: 2469620