JWPR  
Poultry Research  
J. World Poult. Res. 10(2S): 299-325, June 14, 2020  
Journal of World’s  
Research Paper, PII: S2322455X2000036-10  
License: CC BY 4.0  
Development of a Duplex Real-time PCR for Differentiation of  
Salmonella Typhimurium and Monophasic Serovars  
Amany Abd El -Lattief1, Sherif Marouf2, Amany El - Bialy1 and Jakeen El - Jakee2*  
1Animal Health Research Institute, Doki, Giza, Egypt  
2Microbiology Department, Faculty of Veterinary Medicine, Cairo University, Egypt  
*Corresponding author’s E-mail jeljakee@yahoo.com; ORCID: 0000-0002-5299-3783  
Received: 26 Feb. 2020  
Accepted: 05 Apr. 2020  
ABSTRACT  
Salmonella Typhimurium is the most Salmonella serovar causing acute gastroenteritis and diarrhea. Serovar 1, 4, [5],  
12: i:- is considered a monophasic variant of S. Typhimurium that threaten public health. Fifty-eight serologically  
confirmed Salmonella strains were investigated by PCR using 16S rRNA and fliC genes. All 58 strains harbored 16S  
rRNA while 21 strains harbored fliC gene that included S. Typhimurium (12), S. Kentucky (6), Salmonella variant  
strain serotype 1, 4, [5],12:i:- (1), S. Lagos (1), and S. Kedougou (1). A duplex TaqMan real-time PCR was  
performed for differentiating between biphasic S. Typhimurium and monophasic serovar 1, 4, [5], 12:i:- using fljB1,  
2 and fliB/IS200 in the fliA-fliB intergenic region. Ten out of twelve S. Typhimurium harbored fljB 1, 2, while  
Salmonella variant strain serotype 1, 4, [5], 12:i:- lacked this gene. Thirteen strains (12 S. Typhimurium and the  
variant strain serotype 1, 4, [5], 12:i:-) were positive for fliB/IS200 that is a specific gene for S. Typhimurium  
(biphasic and monophasic ). The result of duplex TaqMan real-time PCR indicated that 10 S. Typhimurium strains  
were biphasic while two S. Typhimurium strains and the variant strain serotype 1, 4, [5], 12:i:- lack fljB1,2 and had  
fliB/IS200 were monophasic S. Typhimurium. It is noticed that prolonged subculture and repeat phase inversion  
method leads to the formation of flakes that in turn cause wrongly serotype identification, therefore, real-time PCR is  
rapid and can be used for identifying and differentiating between biphasic and monophasic S. Typhimurium.  
Key words: Biphasic and monophasic S. Typhimurium, flj gene, Real-time PCR, Salmonella.  
INTRODUCTION  
differentiate Salmonella isolates, such as the search for  
genes that can be used as potential molecular substitutes  
for serotyping. However, the genes tested so far have often  
yielded inconsistent results (Osman et al., 2014b; Hua Zou  
et al., 2016). Real-time PCR for detection of Salmonella  
has been brought to inter-laboratory trial, the results of  
which support their use as international standard methods  
Two genomic sites, 16S rRNA and fliC gene have  
been reported as candidates suitable for common and  
specific detection of Genus Salmonella, and S.  
Typhimurium, respectively by real-time PCR (Imre et al.,  
2005). The 16SrRNA can be used for the rapid and  
multiple detections of the 16 pathogenic bacteria  
frequently isolated from contaminated foods that are  
important for food safety (Shin et al., 2016). The 16S  
ribosomal RNA (rRNA), approximately 1500 nucleotides  
in length of the prokaryotic ribosome, provides sufficient  
highly-conserved sequences to design the probes for  
developing microbial detection (Woo et al., 2003). The  
Salmonella enterica is zoonotic bacteria transmitted  
through the food chain and is an important cause of  
2018). It is the second leading cause of bacterial  
2018). The genus Salmonella has a large number of  
serotypes that differ in pathogenicity and host specificity.  
Despite the widespread use of serotyping, it has  
deficiencies that limit its utility, including that it often  
takes three or more days to give a result and  
approximately 5-8% of isolates are partially typed.  
In addition, prolonged subculture can affect the  
antigenic properties of strains. Highly trained laboratories  
are required to type strains accurately, also high costs of  
producing and validity specific antisera to rare antigens  
are problematic (Kim et al., 2006). Delay caused by  
identification can hinder the response to a disease outbreak  
and/ or epidemiological surveillance. Therefore, various  
studies have been explored alternative assays to  
To cite this paper: Abd El-Lattief A, Marouf Sh, El-Bialy A and El-Jakee J (2020). Development of a Duplex Real-time PCR for Differentiation of Salmonella Typhimurium and  
312  
J. World Poult. Res., 10(2S): 299-325, 2020  
fliC gene codes for the Hi antigen of Salmonella targeting  
obtained from Serology Unit, Animal Health Research  
Institute.  
the fliC-i allele greatly increases the specificity for S.  
Typhimurium identification (Pathmanathan et al., 2003).  
S. Typhimurium, according to the White–  
KaufmannLe Minor serotyping scheme (Grimont and  
Weill, 2007), exhibits the antigenic formula 1, 4, [5], 12:  
i:1, 2, where “i” and “1,2” are the first and second flagellar  
antigens expressed by the bacterium at different times,  
hence the serotype description as biphasic (Soyer et al.,  
2009). Antigenic variants that lack either the first or  
second H antigens or both have been described. In recent  
years isolates with antigenic formula 1, 4, [5], 12:i:have  
become increasingly important as a public health risk and  
more frequently recovered from humans and food-  
recommended the confirmation of the serological  
identification of monophasic S. 1, 4, [5], 12:i:- strains  
using a polymerase chain reaction (PCR) protocol based  
on the detection of fljB gene and the fliA-B intergenic  
region. The fljB1,2 gene codes for second phase flagellar  
antigen present in S. Typhimurium. Indeed, all serovar  
Typhimurium strains and its monophasic/ nonmotile  
variants have an IS200 fragment of 1 kb in the fliA-B  
intergenic region, which is not detected in the other  
serovars. Within the flagellin gene cluster of Salmonella  
Phase inversion method  
According to ISO/TR6579 (2014), specific phase  
inversion antiserum was added to a swarm agar medium  
(SIFIN) and the Salmonella strain was spot inoculated on  
the plate. The agar medium shall be sufficiently soft for  
motile Salmonella to swarm over the medium. Slide  
agglutination test was performed from periphery of the  
plate after incubation at 37C˚ for 24 hrs.  
Duplex Syber green real-time PCR  
For the detection of genus Salmonella and S.  
Typhimurium, DNA was extracted from the strains  
according to QIAamp DNA mini kit instructions (Soumet  
et al., 1999 and Yang et al., 2014). SYBR Green real-time  
PCR was performed using oligonucleotide primers (Table  
1) and Quantitect SYBR green PCR kit containing 1ml  
2xQuantiTect SYBR Green PCR Master Mix, 2ml RNase-  
Free Water.  
Table 1.Oligonucleotide primers used in this study for  
detection of genus Salmonella using 16SrRNA and fliC  
genes  
Typhimurium carries  
a
conserved IS200 insertion  
Target  
gene  
sequence located downstream of the flagellin N-methylase  
gene (fliB) and upstream of the flagellar biosynthesis  
sigma factor gene (fliA), this element found in Salmonella  
Typhimurium and its variant (Burnens et al., 1997).  
Several studies have reported DNA sequences for  
Salmonella flagellin genes. As of June 2003, 74 complete  
or partial Salmonella fliC alleles and 25 complete or  
partial Salmonella fljB allele sequences had been  
documented in GenBank release no. 132, excluding  
complete genome sequences.  
Thus, this study aimed, first, to confirm Salmonella  
strains using 16SrRNA gene and S. Typhimurium using  
fliC by Syber green-based real-time PCR, and second, to  
differentiate between S. Typhimurium and monophasic  
serovar 1, 4, [5], 12:i:- using fljB1,2 and IS200 in the fliA-  
fliB region using TaqMan real-time PCR.  
Primer sequence (5'-3')  
Reference  
F: CAGAAGAAGCACCGGCTAACTC  
R: GCGCTTTACGCCCAGTAATT  
16S  
rRNA  
Yang et al.,  
2014  
F: CGGTGTTGCCCAGGTTGGTAAT  
R: ACTCTTGCTGGCGGTGCGACTT  
Soumet et al.,  
1999  
fliC  
F: forward, R: reverse  
Table 2. Oligonucleotide primers and probes used for  
differentiating between biphasic Salmonella Typhimurium  
and monophasic serovar 1, 4, [5], 12:i:- using fljB1,2 and  
fliB/IS200 in the fliA-fliB intergenic region.  
Target  
Primer sequence (5'-3') and probe  
Reference  
F: TGT TAC TAT TGG TGG CTT TAC  
TGG  
fljB1, 2  
R: CAG CAG GCA TTG TGG TCT TAG  
FAM- CGC CAG CCG CAA GGG TTA  
CTG TAC TAMRA  
Prendergast  
et al., 2013  
MATERIALS AND METHODS  
F: GAT CTG TCG ATG ATT CAT CTT  
CTG AC  
fliB/1S200 R: AAC GCT TGT CTT CGG TAT TTG G  
Strains  
CY5-TCG GGT GTG CGC TAA GCT CTT  
TT -BHQ1  
A total of 58 Salmonellae isolates recovered from  
chicken in previous work (Abd El-Lattief, 2014), was  
identified serologically by slide agglutination test  
F: forward, R: reverse  
313  
Abd El-Lattief et al., 2020  
Differentiation of S. Typhimurium and  
monophasic 1, 4, [5], 12:i:-by TaqMan real-time PCR  
TaqMan real-time PCR was performed according to  
Prendergast et al. (2013) using oligonucleotide primers  
and probes presented in table 2, and the Quantitect probe  
real-time PCR kit (Qiagen).  
Phylogenetic analysis  
A comparative analysis of sequences was performed  
using the CLUSTAL W multiple sequence alignment  
program, version 1.83 of MegAlign module of Lasergene  
DNA Star software Pairwise, which was designed by  
Thompson et al. (1994) and phylogenetic analyses were  
done using maximum likelihood, neighbor-joining and  
maximum parsimony in MEGA6 (Tamura et al., 2013).  
fliC sequencing  
fliC was sequenced using fliC primer presented in  
table 1. A purified PCR product was sequenced in the way  
of the forward and/ or reverse directions on an Applied  
Biosystems 3130 automated DNA Sequencer (ABI, 3130,  
USA), using a ready reaction Bigdye Terminator V3.1  
cycle sequencing kit (Perkin-Elmer/Applied Biosystems,  
Foster City, CA).  
RESULTS  
Serotyping of Salmonella  
The Serotyping of the 58 Salmonella strains was  
confirmed and the result is presented in table 3.  
Table 3. Antigenic structure of all Salmonella strains recovered using slide agglutination test.  
No  
Serotyping  
No  
30-  
31-  
32-  
33-  
34-  
35-  
36-  
37-  
38-  
39-  
40-  
41-  
42-  
43-  
44-  
45-  
46-  
47-  
48-  
49-  
50-  
51  
Serotyping  
Name  
Name  
1-  
8,20 :i:z6  
13,22 :m,t:–  
S. Kentucky  
S. Lagos  
S. Washington  
S. Newport  
2-  
1,4,5,12:i:1,5  
1,4,[5],12:i:1,2  
1,4,[5],12:i:1,2  
1,3,19: i: z6  
6,8,20 :e,h :1,2  
1,9,12 : g,m:–  
6,7,14 :f,g:-  
3-  
S. Typhimurium  
S. Typhimurium  
S. Taksony  
S. Derby  
S. Enteritidis  
S. Rissen  
4-  
5-  
S. Labadi  
8,20 :d: z6  
6-  
1,4,[5],12:f,g:-  
6,7,14:f,g:-  
1,9,12 : g,m: –  
1,3,19: g,[s],t :–  
6,14,18 :z4,z23 :[1,5]  
8: d :1,2  
S. Enteritidis  
S. Senftenberg  
S. Cerro  
7-  
S. Rissen  
8-  
1,4,[5],12:i:1,2  
3,{10} {15} {15,34} :e,h: 1,6  
1,4,[5],12:i:1,2  
1,2,12: a: [1,5]  
1,4,[5],12 :b: 1,2  
1,13,23: i :l,w  
8,20 :d: z6  
S. Typhimurium  
S. Anatum  
9-  
S. Virginia  
10-  
11-  
12-  
13-  
14-  
15-  
16-  
17-  
18-  
19-  
20-  
21-  
22-  
23-  
24-  
25-  
26-  
27-  
28-  
29-  
6,7 :r :e,n,z15  
1,4,[5],12:i:1,2  
1,4,[5],12:i:1,2  
8,20: i: z 6  
S. Typhimurium  
S. Paratyphi A  
S. Paratyphi B  
S. Kedougou  
S. Labadi  
S. Papuana  
S. Typhimurium  
S. Typhimurium  
S. Kentucky  
S. Typhimurium  
S. Enteritidis  
S. Virginia  
1,4,[5],12:i:1,2  
1,9,12 :g,m: –  
8:d:1,2  
S. Poona  
1,13,22: z: 1,6  
1,4,[5],12:i:1,2  
8,20: i :z6  
S. Typhimurium  
S. Kentucky  
S. Anatum  
S. Kentucky  
S. Washington  
S. Enteritidis  
S. Newlands  
S. Gallinarum  
S. Agama  
8,20: i :z 6  
3,{10}{15}{15,34} :e,h: 1,6  
6,8 :r :l,w  
13,22 :m,t:–  
1,9,12:g,m: –  
3,{10} {15 ,34}:e,he,n,x:-  
1,9,12 :: –  
S. Goldcoast  
S. Enteritidis  
S. Infantis  
1,9,12:g,m:-  
6,7,14: r :1,5  
1,9,12: :–  
4,12:i:1,6  
S. Gallinarum  
S. Gallinarum  
S. Hadar  
1,9,12: :–  
52-  
53-  
54-  
55-  
56-  
57-  
58-  
S. Kentucky  
S. Kentucky  
S. Typhimurium  
S. Typhimurium  
S. Typhimurium  
Partial identification  
S. Typhimurium  
8,20: i: z 6  
6,8 :z10:e,n,x  
6,7,14: r :1,2  
6,7,14: r :1,2  
6,8 :z10 :e,n,x  
8 :e,h:1,2  
8,20: i :z 6  
1,4,[5],12:i:1,2  
1,4,[5],12 :i :1111,2  
1,4,[5],12:i:1,2  
1,4,[5],12:i:-  
1,4,[5],12:i:1,2  
S. Virchow  
S. Virchow  
S. Hadar  
S. Bardo  
6,7,14 :g,m,s :-  
S. Montevideo  
314  
J. World Poult. Res., 10(2S): 299-325, 2020  
Syber Green real-time duplex PCR  
lacked this gene. Concerning fli B/IS200, the 13 strains  
possess fliB/IS200 (12 S. Typhimurium and the variant  
strain S 1, 4 ,[5], 12:i:-) (Table 5 and figure 3).  
All 58 strains belonged to genus Salmonella were  
positive by SYBER green real-time PCR using 16S rRNA.  
The specificity of the reaction was confirmed by melting  
temperature (Tm) which was consistently specific for  
amplicon obtained; the mean peaks Tm obtained. The  
negative control did not show peaks in the Tm when  
subjected to 40 cycles of amplification. Twenty-one  
Salmonella strains harbored fliC gene, including S.  
Typhimurium (12), S. Kentucky (6), S. Lagos (1), S.  
Kedougou (1) and partial identified strain S 1,4, [5],12:i:-  
which possess first flagellar i antigen (Table 4; figures 1  
and 2). A total of 15 strains were positive for fljB 1,2. Ten  
strains of Salmonella Typhimurium and serovars Paratyphi  
A (1) & Paratyphi B (1) & Newport (1) and Virginia (2)  
harbored fljB1,2, while strain no.57 with antigenic formula  
1, 4 ,[5], 12:i:- and two strains Salmonella Typhimurium  
fli C Sequencing  
Individual Salmonella serotypes usually alternate  
between the production of 2 antigenic forms of flagella,  
termed phase 1 and phase 2, each specified by separate  
structural genes, fliC and fljB 1, 2. Sequencing of fliC gene  
based on the nucleotide sequence of S.Typhimurium13311  
referenced in GenBank illustrated that the biphasic S.  
Typhimurium strain was recorded in GenBank as S.  
Typhimurium Egy 1 with accession number Mk103394  
and the monophasic strain as S. Typhimurium Egy 2 with  
accession number MK 103395. The amino acid sequence  
of the fliC gene in the two isolates showing greater than  
98% identity.  
Table 4. Detection of 16SrRNA and fliC genes in Salmonella serovars using duplex Syber green real-time PCR  
No.  
1
Name  
S. Kentucky  
S. Lagos  
16S RNA  
fliC  
+
+
+
+
-
No.  
30  
31  
32  
33  
34  
35  
36  
37  
38  
39  
40  
41  
42  
43  
44  
45  
46  
47  
48  
49  
50  
51  
52  
53  
54  
55  
56  
57  
58  
Name  
16S rRNA  
fliC  
-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
S. Washington  
S. Newport  
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
2
-
3
S. Typhimurium  
S. Typhimurium  
S. Taksony  
S. Derby  
S. Enteritidis  
S. Rissen  
-
4
-
5
S. Labadi  
-
6
-
S. Enteritidis  
S. Senftenberg  
S. Cerro  
-
7
S. Rissen  
-
-
8
S. Typhimurium  
S. Anatum  
+
-
-
9
S. Virginia  
-
10  
11  
12  
13  
14  
15  
16  
17  
18  
19  
20  
21  
22  
23  
24  
25  
26  
27  
28  
29  
S. Typhimurium  
S. Paratyphi A  
S. Paratyphi B  
S. Kedougou  
S. Labadi  
+
-
S. Papuana  
-
S. Typhimurium  
S. Typhimurium  
S. Kentucky  
S. Typhimurium  
S. Enteritidis  
S. Virginia  
+
+
+
+
-
-
+
-
S. Poona  
-
S. Typhimurium  
S. Kentucky  
S. Anatum  
+
+
-
-
S. Kentucky  
S. Washington  
S. Enteritidis  
S. Newlands  
S. Gallinarum  
S. Agama  
+
-
S. Goldcoast  
S. Enteritidis  
S. Infantis  
-
-
-
-
-
-
S. Gallinarum  
S. Gallinarum  
S. Hadar  
-
-
-
S. Kentucky  
S. Kentucky  
S. Typhimurium  
S. Typhimurium  
S. Typhimurium  
1,4,[5],12:i:-  
S. Typhimurium  
+
+
+
+
+
+
+
-
S. Virchow  
S. Virchow  
S. Hadar  
-
-
-
S. Bardo  
-
S. Montevideo  
-
315  
Abd El-Lattief et al., 2020  
Table 5. Detection of fljB1,2 and fliB/IS200 in Salmonella serovars using duplex TaqMan real-time PCR  
No.  
Name  
S. Kentucky  
S. Lagos  
fljB1,2  
fliB/IS200  
ND  
ND  
+
No.  
30  
31  
32  
33  
34  
35  
36  
37  
38  
39  
40  
41  
42  
43  
44  
45  
46  
47  
48  
49  
50  
51  
52  
53  
54  
55  
56  
57  
58  
Name  
fljB1,2  
fliB /IS200  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
+
1
-
-
S. Washington  
S. Newport  
-
+
-
2
3
S. Typhimurium  
S .Typhimurium  
S. Taksony  
S. Derby  
+
+
-
S. Enteritidis  
S. Rissen  
4
+
-
5
ND  
ND  
ND  
+
S. Labadi  
-
6
-
S. Enteritidis  
S. Senftenberg  
S. Cerro  
-
7
S. Rissen  
-
-
8
S. Typhimurium  
S. Anatum  
+
-
-
9
ND  
+
S. Virginia  
+
-
10  
S. Typhimurium  
S. Paratyphi A  
S. Paratyphi B  
S. Kedougou  
S. Labadi  
+
+
+
-
S. Papuana  
11  
ND  
ND  
ND  
ND  
ND  
+
S. Typhimurium  
S. Typhimurium  
S. Kentucky  
S. Typhimurium  
S. Enteritidis  
S. Virginia  
+
+
-
12  
+
13  
ND  
+
14  
-
+
-
15  
S. Poona  
-
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
+
16  
S. Typhimurium  
S. Kentucky  
S. Anatum  
+
-
+
-
17  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
ND  
S. Kentucky  
S. Washington  
S. Enteritidis  
S. Newlands  
S. Gallinarum  
S. Agama  
18  
-
-
19  
S. Goldcoast  
S. Enteritidis  
S. Infantis  
-
-
20  
-
-
21  
-
-
22  
S. Gallinarum  
S. Gallinarum  
S. Hadar  
-
-
23  
-
S. Kentucky  
S. Kentucky  
S. Typhimurium  
S. Typhimurium  
S. Typhimurium  
S. Typhimurium  
S. Typhimurium  
-
24  
-
-
25  
S. Virchow  
S. Virchow  
S. Hadar  
-
+
-
26  
-
+
27  
-
-
+
28  
29  
S. Bardo  
-
-
+
S. Montevideo  
-
+
+
ND: Not detected  
316  
J. World Poult. Res., 10(2S): 299-325, 2020  
Figure 1. Syber green real-time PCR targeting 16S rRNA gene for 58 Salmonella strains isolated from chickens (fluorescence  
chart and melting curve). A) Fluorescence chart for strains number 1 to 29. B) Fluorescence chart for strains number 30 to 58.  
(Amplification plots represent the accumulation of product over the duration of real-time PCR). C) Melting curve for strain  
number 1 to 29. D) Melting curve for strain number 30 to 58. Melting curve provides representation of the PCR product after  
the amplification process, A single peak indicates a positive sample. All 58 strains isolated from chickens were positive for  
16SrRNA gene. The specificity of the reaction was confirmed by the melting temperature. The mean peak temperature  
obtained was 80.55 °C.  
317  
Abd El-Lattief et al., 2020  
Figure 2. Syber green real-time PCR targeting fliC gene for 58 Salmonella strains isolated from chicken (fluorescence chart  
and melting curve). A) Fluorescence chart for strains number 1 to 29. B) Fluorescence chart for strains number 30 to 58  
(Amplification plots represent the accumulation of product over the duration of real-time PCR). C) Melting curve for strain  
number 1 to 29, where strains number 1, 2, 3, 4, 8, 10, 13, 16 and 17 gave positive results. D) Melting curve for strain number  
30 to 58, where strains number 40, 41, 42, 43, 46, 52, 53, 54, 55, 56, 57 and 58 gave positive result . (Melting curve provide  
representation of the PCR product after the amplification process. A single peak indicates a positive sample. Twenty-one  
Salmonella strains harbored fliC gene. The specificity of the reaction was confirmed by melting temperature, the mean peak  
temperature obtained was 85.65 °C.  
318  
J. World Poult. Res., 10(2S): 299-325, 2020  
method. The strain was considered monophasic when  
phase inversion method was repeated at least three times  
without getting expression of phase 2 flagellar antigen as  
shown in strain number 57 with antigenic formula S.1, 4,  
[5], 12:i:-. Grimont and Weil (2007) mentioned that S.1, 4,  
[5], 12:i:- does not appear in the White-Kaufmann-Le  
Minor scheme and appears to be a monophasic variant of  
other biphasic serovars, which have lost phase 2 flagellin  
or the necessary switching mechanism of phase variation.  
Seven serovars of S. enterica subsp. enterica with the same  
O and phase 1 H antigens are possible ancestors of this  
serovar, including S. Typhimurium, S. Lagos, S. Agama, S.  
Farsta, S. Tsevie, S. Gloucester, and S. Tumodi. Among  
these, S. Typhimurium monophasic S.1, 4, [5], 12:i:- is  
commonly isolated from humans, animals, and the  
environment.  
In recent years, many studies try to establish  
methods that can reduce the time for the detection and  
identification of salmonellae. Detection of bacteria by  
conventional methods is time-consuming and allows the  
detection of viable one only (Kim et al., 2006).  
Figure 3. TaqMan real-time PCR amplification chart for  
fljB1,2 gene among 58 Salmonella strains isolated from  
chickens. Typical amplification curves given for positive  
samples. Fifteen strains (number 3, 4, 8, 10, 11, 12, 16, 31,  
38, 40, 41, 43, 45, 54 and 58) gave positive results.  
The use of PCR has emerged as an approach to  
overcome these problems. The exploration of gene targets  
for evaluation of absence and presence of bacteria is still a  
matter of importance. Several genes invA, fimA, and aceK  
were used for identification of genus Salmonella (O’Regan  
et al., 2008). The duplex Syber green real-time PCR was  
applied for detection of genus Salmonella and the most  
common serovar S. Typhimurium based on melting Temp  
(TM) and Curve analysis using 16S rRNA and fli C genes  
respectively. 16 S rRNA not only allow the presence of  
bacteria to be proved but also would give information on  
gene expression .However, the expression of rRNA is  
S rRNA (Table 4 and figure 1).  
Figure 4. TaqMan real-time PCR amplification chart for  
fliB/IS200 gene among 13 Salmonella isolates (12 S.  
Typhimurium and the variant strain serotype 1, 4, [5],  
12:i:-) (fliB/IS200 is a specific gene for S. Typhimurium  
biphasic and monophasic ). Thirteen strains ( number 3, 4,  
8, 10, 16, 40, 41, 43, 54, 55, 56, 57 and 58) gave positive  
results.  
16SrRNA gene sequences contain hypervariable  
regions that can allow species-specific signature sequences  
important for identification of bacteria. The 16 SrRNA  
gene is used as the standard for classification and  
identification of bacteria because it is present in most  
microbes and shows proper changes. 16 SrRNA gene  
sequences for most bacteria are available on public  
databases such as NCBI (Pereira, 2010). Attractive  
potential uses of 16 S rRNA gene sequence informatics for  
providing genus and species identification.  
DISCUSSION  
Serological identification of 58 Salmonella strains was  
confirmed by slide agglutination test and the antigenic  
structure is demonstrated in table 3. Failure to identify the  
complete antigenic formula prevents the unequivocal  
identification of serovars even after phase inversion  
The fliC target is specific for the phase-1 flagellar  
antigen i that encoded by serovars Typhimurium. In the  
present study twenty one strains possess fliC gene serovars  
Typhimurium (12), Kentucky (6), Kedougou (1), Lagos  
319  
Abd El-Lattief et al., 2020  
(1) and S .1,4, [5], 12:i:-.(1) (Table 4 and figure 2). O'  
yield1000-bp amplicon with conventional PCR. These  
data suggest that S. 1, 4, [5], 12:i:- is a monophasic variant  
of S. Typhimurium (Burnens et al., 1997). Also, they  
reported that within the flagellin gene cluster of  
Salmonella, S. Typhimurium carries a conserved IS200  
insertion sequence located downstream of the flagellin N-  
methylase gene (fliB) and upstream of the flagellar  
biosynthesis sigma factor gene (fliA). In the present study  
ten strains yield positive result with fliC , fljB1,2 and fliB/  
IS200 were biphasic Salmonella Typhimurium meanwhile  
3 strains harbored the fliC and fliB/ IS200 were  
monophasic strains S 1, 4,[5],12:i:- (Table 6) .  
During recent years the cost of sequencing has been  
reduced dramatically making sequencing based typing  
more attractive. Some studies have reported DNA  
sequence for flagellin gene (Silverman, 1979; Joys, 1985  
and De Vries, 1998). As in 2016, fliC sequence (partial  
coding sequence) has reported in GenBank with accession  
no DQ095491. This study reported sequencing of fliC  
gene for two strains S. Typhimurium and monophasic  
variant S 1, 4,[5],12:i:- with accession no (Mk103394) and  
(Mk103395), respectively.  
Regan et al. (2008) reported that the i antigen is also  
expressed in uncommon serotypes such as Aberdeen,  
Bergen, and Kedougou. The structural flagellin gene fliC  
was present in all isolates of serovars Typhimurium and  
Kentucky (full length) and in all isolates of serovars  
Heidelberg, Hadar, and Enteritidis (partial length)  
Most S. enterica serovar Typhimurium possess two  
different flagellin proteins, including FliC (phase 1) and  
FljB (phase 2), which are encoded by the genes fliC and  
(EFSA) (2010) applied a conventional PCR protocol to  
confirm the absence of 2nd phase antigen. A real- time  
PCR assay was used to differentiate S. Typhimurium  
monophasic variants from biphasic S. Typhimurium and  
Fifteen isolates are positive for fljB1,2 S.  
Typhimurium (10), S. Paratyphi A(1) , S. Paratyphi B(1) ,  
S. Newport (1) and S. Virginia (2) (Table 5 and figure 3).  
This result agree with that published by Bugarel et al.  
(2012) who reported that the second gene codes for the  
phase 2 flagellar antigen fljB1,2 is present in S.  
Typhimurium and other serovars such as S. Coeln, S.  
Haifa, S. Heidelberg, S. Paratyphi B, S. Saintpaul and S.  
Stanley. This marker is absent in monophasic S.  
Protein sequence is the practical process of  
determining the amino acid sequence of all or part of  
protein or peptide. About 500 naturally occurring amino  
acids are known, 20 only appear in the genetic code there  
Typhimurium.  
Two  
serologically  
identified  
S.  
are termed as codons are always 3 Base pairs  
Typhimurium strains no. 55 ,56 don’t possess fljB1,2 that  
could be explained by repeat phase inverted method leads  
to formation of flakes which may lead to misidentification  
or wrongly identified strains.  
(nucleotides). In this study, amino acid sequence were  
applied for the fliC gene. In the location 14-19 sequence  
TNGKVT was found, which is similar to sequences coded  
in GenBank with accession no. CP024619, LT795114,  
CP014979, but in other sequences reported in GenBank  
with accession no. CP026700, CP021462, CP028199  
glutamic acid was found between GK with amino acid  
sequence TNGEKVT (Figure 5).  
In this study, the amino acid threonine was absent at  
position 24 in S. Typhimurium Egy1 and S. Typhimurium  
Egy2, which is similar to sequences recorded in GenBank  
with accession no. CP014979, CP014967. While the result  
disagreed with sequences coded in GenBank with  
accession number CP007581 and DQ09549 which have  
threonine at position 24 between glycine and alanine.  
At position 60-65 found amino acid sequence  
AGVTGT in S. Typhimurium Egy1 and S. Typhimurium  
Egy2, but in sequence coded in GenBank with accession  
no. LN999997 amino acid alanine at positin 65 between  
glysine and threonine was found. Alignments show highly  
degree of identity. There are greater than 98% amino acid  
sequence identity (Figures 6 and 7). This is according to  
Flagellar phase variation is formed by inversion of  
the genetic region called the H segment, which have the  
hin gene encoding for DNA invertase and the promoter for  
the fljB gene. The fljB constitutes an operon with the fljA  
gene, which encodes a negative regulator of fliC  
expression. FljA binds to the operator region of FliC  
mRNA and inhibits its translation, leading to the rapid  
degradation of FliC mRNA. When the H segment is in the  
“on” state, both fljB and fljA are transcribed, lead to  
synthesis of phase 2 flagellin and inhibition of phase 1  
flagellin. However, when the H segment is switched to the  
“off” state, neither fljB nor fljA are transcribed, resulting in  
the synthesis of phase 1 flagellin only (Ido et al., 2014).  
The location of IS200 between the genes fliA and  
fliB can be used as a specific marker for S. Typhimurium.  
The amplicon sizes from the fliAfliB intergenic regions  
from S. Typhimurium and other serovars were expected to  
be 1000 and 250 bp, respectively. TaqMan real-time PCR  
could successfully detected S. 1, 4, [5], 12:i:- isolates that  
320  
J. World Poult. Res., 10(2S): 299-325, 2020  
Table 6. Comparison between results of conventional serotyping and real-time PCR for Salmonella Typhimurium (biphasic  
and monophasic strains)  
Conventional serotyping  
Phase 1 H Phase 2 H  
Real -time PCR  
No. of isolate  
Name of isolate  
O antigen  
fliC  
+
fljB1,2  
fliB/IS200  
antigen  
antigen  
Salmonella Typhimurium  
10 strains  
3 strains  
1 strain  
4,[5],12  
4,[5],12  
4,[5],12  
4,[5],12  
I
1,2  
+
-
+
+
-
(diphasic)  
Salmonella Typhimurium  
Not  
detected  
I
I
-
+
monophasic)  
Non-Salmonella  
Typhimurium  
+
-
Non Salmonella  
Typhimurium  
5strains  
1,2  
-
+
-
321  
Abd El-Lattief et al., 2020  
Figure 5. Amino acid sequence alignment report for fliC gene of two Egyptian Salmonella strains recorded in GenBank with  
accession number Mk103394 and Mk103395 for S. Typhimurium Egy 1(biphasic) and S. Typhimurium Egy 2 (monophasic),  
respectively. The sequence alignment of two Egyptian strains is 100% similar to nine strains recorded in GenBank (S.  
Typhimurium BL10, S. Typhimurium VNB151 , S. Typhimurium CDC H2662 , S. Typhimurium 81741 , S. Typhimurium  
USDA-ARS-USMA, S. Typhimurium CDC2011K-1702, S. Typhimurium RM9437, S. Typhimurium 33676 and S.  
Typhimurium SGSC2193). In the location 14-19, sequence TNGKVT was found for two Egyptian strains that matched  
sequences of some strains coded in GenBank with accession no. CP024619, LT795114, and CP014979, but in other strains  
reported in GenBank with accession no. CP026700, CP021462, and CP028199 glutamic acid was found between GK and  
amino acid sequence was TNGEKVT. The amino acid threonine was absent at position 24 in S. Typhimurium Egy1 and S.  
Typhimurium Egy2, but strains recorded in GenBank with accession no. CP007581 and DQ09549 have threonine at position  
24 between glycine and alanine. At position 60-65 aminoacid sequence AGVTGT was found in S. Typhimurium Egy1 and S.  
Typhimurium Egy2, but in a sequence coded in GenBank with accession no. LN999997 amino acid alanine was found at  
position 65 between glycine and threonine.  
322  
J. World Poult. Res., 10(2S): 299-325, 2020  
Figure 6. Amino acid sequence distance performed using the CLUSTAL W multiple sequence alignment program and version  
1.83 of MegAlign module of Lasergene DNAStar software Pairwise for fliC gene among two Egyptian Salmonella strains (S.  
Typhimurium Egy 1(biphasic) and S. Typhimurium Egy 2 (monophasic)).  
Figure 7. Phylogenetic analysis of Salmonella Typhimurium using fliC gene sequence performed by maximum likelihood,  
neighbor-joining and maximum parsimony implemented in MEGA6. The amino acid sequence of two Egyptian strain  
(Mk103394 and Mk103395) were closely related to sequences recorded in GenBank (CP024619 for S. Typhimurium BL10,  
LT795114 for S. Typhimurium VNB151, CP014979 for S. Typhimurium CDC H2662, CP019442 for S. Typhimurium  
81741, CP014969 for S. Typhimurium USDA-ARS-USMA, CP014967 for S. Typhimurium CDC2011K-1702, CP012985  
for S. Typhimurium, CP012681 for S. Typhimurium 33676RM9437 and AY649718 for S. Typhimurium SGSC2193).  
323  
Abd El-Lattief et al., 2020  
Grimont PAD and Weill FX (2007). Antigenic Formulas of the  
CONCLUSION  
Salmonella Serovars, 9thedition. WHO Collaborating Centre for  
Reference and Research on Salmonella. Institute Pasteur, Paris.  
The duplex real-time PCR is a rapid and robust method for  
detection of genus Salmonella and can be used for  
identification and differentiation of S. Typhimurium and  
the most common variant S.1, 4, [5], 12:i:-.  
Hopkins KL, Kirchner M, Guerra B, Granier SA, Lucarelli C and Porrero  
MC (2010). Multi resistant Salmonella enterica serovar 4, [5],  
12:i:- in Europe: a new pandemic strain. Eurosurveillance Journal,  
Hua Zou Q, Qing Li R , Rong Liu G and Lin Liu S (2016). Genotyping  
of Salmonella with lineage-specific genes: correlation with  
DECLARATIONS  
Ido N, Lee KI, Iwabuchi K, Izumiya H and Uchida I (2014) .  
Characteristics of Salmonella enterica Serovar 4, [5], 12:i:- as a  
Monophasic Variant of Serovar Typhimurium. PLoS ONE, 9(8):  
e104380. DOI: https:/ /doi.org /10.1371 /journal .pone.0104380.  
Acknowledgments  
This study was supported by the research group of  
Animal Health Research Institute, Egypt  
Imre A, Olasz F and Nagy B (2005). Development of a PCR system for  
the characterisation of Salmonella flagellin genes. Acta Veterinaria  
Competing interests  
The authors have declared that no competing interest  
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ISO/TR6579 -3 (2014). Microbiology of food chain horizontal method  
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