Logo of eidLink to Publisher's site
Emerg Infect Dis. 2010 Nov; 16(11): 1754–1757.
PMCID: PMC3294505

Multidrug-Resistant Salmonella enterica Serovar Infantis, Israel


To determine whether rapid emergence of Salmonella enterica serovar Infantis in Israel resulted from an increase in different biotypes or spread of 1 clone, we characterized 87 serovar Infantis isolates on the genotypic and phenotypic levels. The emerging strain comprised 1 genetic clone with a distinct pulsed-field gel electrophoresis profile and a common antimicrobial drug resistance pattern.

Keywords: Bacteria, Salmonella, enteric infections, foodborne infections, Salmonella enterica, Infantis, serovars, antibicrobial resistance, Israel, dispatch

Nontyphoid Salmonella enterica (NTS) is a common cause of foodborne illnesses worldwide. In industrialized countries, S. enterica serovars Enteritidis and Typhimurium are responsible for most NTS infections (1). In Israel, the distribution of NTS infections differs from the global epidemiology for NTS by having a larger representation of serogroups C1 and C2 (serovars Virchow, Hadar, and Infantis) in addition to serovars Enteritidis and Typhimurium (2,3).

Analysis of annual trends of NTS infections in Israel during 1995–2009 shows a steady decrease in the incidence of these infections, from 86.9 cases/100,000 persons in 1995 to 31.4/100,000 in 2005. During this period, the predominant serovars were Enteritidis, Typhimurium, Virchow, and Hadar, followed by Infantis. Since 2006, annual incidence of NTS has started to increase, rising to 44.0 cases/100,000 persons in 2009. This trend coincided with a sharp increase in incidence of serovar. Infantis from 1.2 cases/100,000 persons in 2001 to 14.7/100,000 in 2009, a 12-fold rise (Figure 1, panel A). The proportion of serovar Infantis increased from <10% of NTS in 1995–2005 to 34% in 2009 (Figure 1, panel B). Furthermore, this steep increase in serovar Infantis from clinical (human) sources correlated with an elevated frequency of serovar Infantis from poultry that became apparent after 2006. Serovar Infantis became the predominant serotype in poultry during 2007–2009, while the prevalences of serovars Enteritidis, Typhimurium, Virchow, Bredeney, Newport, and Paratyphi B var. Java decreased (Figure 1, panel C).

Figure 1
Salmonellosis epidemiology in Israel, 1995–2009. A) Annual incidence of salmonellosis in Israel. Laboratory-confirmed cases of Salmonella infections per 100,000 population caused by all Salmonella serotypes (black) and by the 5 leading serotypes ...

The Study

Molecular analysis was used to study whether the rapid emergence of S. enterica ser. Infantis resulted from a general increase in different biotypes or a successful spread of 1 clone. Seventy-one randomly selected isolates of S. enterica ser. Infantis identified in Israel during 2007–2009 (21 human sources, 28 poultry sources, and 22 food sources) and 16 historical strains isolated during 1970–2005 (12 human sources, 2 poultry sources, and 2 food sources) were subjected to pulsed-field gel electrophoresis (PFGE). Macrorestriction with the XbaI enzyme discriminated the isolates into 23 distinct profiles (pulsotypes), designated I1–I23. Although the historical isolates showed high diversity in their PFGE patterns, most (58/71, 82%) recent (2007–2009) isolates were homogeneous and showed an indistinguishable PFGE profile (pulsotype I1), which was not found among the historical isolates (Figure 2; Table A1). These results indicate that most of the emerging isolates belong to 1 genetic clone that probably started to spread in Israel sometime during 2005–2007. Furthermore, comparison of the I1 pulsotype with other PFGE profiles through PulseNet (www.cdc.gov/pulsenet/) and PulseNet Europe (www.pulsenetinternational.org/networks/europe.asp) indicated a pattern not reported elsewhere, suggesting the emerging clone is endemic to Israel.

Figure 2
Pulsed-field gel electrophoresis (PFGE) patterns of Salmonella enterica serovar Infantis isolates from clinical, food, and poultry sources isolated in Israel, 1970–2009, showing a high degree of clonality. Isolate number, year of isolation, and ...

To further characterize the isolates, we performed susceptibility tests to 16 antimicrobial compounds. Overall, resistance to 11 antimicrobial agents was detected (Table; Table A1). Two clear differences were found between the strains isolated before and after 2007. First, although 6/16 (38%) of the historical strains were sensitive to all tested antimicrobial agents and 5/16 (31%) were resistant to only 1 (nitrofurantoin), none of the 2007–2009 isolates were sensitive to all of the tested antimicrobial agents. Most (68/71, 96%) of the recent isolates were resistant to >3 antimicrobial agents, which suggests a process of resistance acquisition over time. Second, whereas isolates from 1970–2005 did not share any obvious resistance pattern, most (66/71, 93%) of the 2007–2009 strains showed a combined resistance pattern to nalidixic acid, nitrofurantoin, and tetracycline with or without additional resistance to trimethoprim/sulfamethoxazole (Table). The convergence of the recent serovar Infantis clones to a dominant resistance pattern is consistent with their common PFGE profile and shows that they share high similarity on phenotypic and genotypic levels.

Antimicrobial drug resistance patterns of Salmonella enterica serovar Infantis isolates, sorted by isolation year, Israel*

Next, we characterized the molecular mechanisms responsible for the common antimicrobial drug–resistance phenotype. In bacteria, an efficient means of acquisition and dissemination of resistance genes is through mobile genetic elements such as plasmids, transposons, or integrons (5). Plasmid analysis for 15 emerging (2007–2009) and 7 historical (1970–2005) randomly selected isolates demonstrated that all possessed 1 large plasmid of ≈100 kb. To identify antimicrobial drug resistance genes that are possibly encoded on this plasmid, mating experiments were conducted with a plasmid-free, rifampin-resistant Escherichia coli J5–3 strain and recent S. enterica ser. Infantis isolates harboring tetracycline, nalidixic acid, and nitrofurantoin resistance genes. Conjugation experiments showed the obtained E. coli transconjugants received the large (≈100-kb) plasmid and acquired the tetracycline resistance phenotype but remained susceptible to nalidixic acid and nitrofurantoin. We concluded the tetracycline resistance gene(s) is encoded on the conjugative plasmid. Molecular analysis by PCR showed the tetA gene encoded within the Tn1721 transposon in 6 of 6 randomly selected emerging isolates but in only 1 of 5 older historical strains.

We examined class 1 integrons using PCR primers designed to amplify the variable region of class 1 integrons. All 6 recent isolates bore 1 integron with a variable region of ≈1 kb. Sequencing of the resulting amplicon showed the dfrA1 gene cassette conferring resistance to trimethoprim–sulfamethoxazole followed by the orfC gene of unknown function. In contrast, 3/5 historical isolates did not possess any integron, and 2/5 contained a disparate integron with a variable region of ≈1.3 kb. Sequencing analysis indicated a different cassette encoded by the aminoglycoside adenyltransferase aadA1 gene conferring resistance to spectinomycin and streptomycin.

Resistance to quinolones is often associated with point mutations in the quinolone-resistance determining region of the gyrA gene (6). To examine this possibility, we determined the gyrA sequence from 6 recent naladixic acid–resistant and 4 naladixic acid–sensitive isolates. All resistant clones showed the same nucleotide substitution from guanine to thymine at position 259 (G259T) in the gyrA gene, resulting in the exchange of asparagine in position 87 to tyrosine (Asp87Tyr) in the quinolone resistance–determining region domain. No mutations were found in the gyrA sequence of the naladixic acid–sensitive isolates, suggesting that the Asp87Tyr point mutation is responsible for the observed naladixic acid–resistance phenotype.


It is likely that environmental selective pressure caused by use of antimicrobial drugs has led to the distribution of appropriate resistant genes. Nitrofurans and sulfonamides, for example, have been widely used to treat infections and promote growth of livestock (7). Because the emerging clone was dominant in all levels of the food chain, including broiler chickens, it is possible that the emerging clone was originally introduced from a poultry source. Recent studies from other countries identified healthy poultry as a potential reservoir of S. enterica ser. Infantis (810).

Molecular and phenotypic characterization of recent S. enterica ser. Infantis isolates from different sources and regions in Israel showed high homogeneity of emerging isolates that differ genetically and phenotypically from previously isolated strains. We showed that the emerging clone is multidrug resistant and is characterized by a large conjugative plasmid harboring the Tn1721 transposone and tetA gene, which provides reduced susceptibility to tetracyclines. Additional characteristics include a class 1 integron containing the dfrA1 cassette, a gyrA mutation that mediates nalidixic acid resistance and furthers resistance to nitrofurantoin. Our results suggest the recent emergence of serovar Infantis is an outcome of a clonal expansion and establishment of a specific biotype that took place during a relatively short period. Virulence mechanisms contributing to this phenomenon are the subject of an ongoing study.


We thank Noemi Nógrády for providing the Escherichia coli J5-3 RifR strain.

This study was supported by funding from the European Community's Seventh Framework Program (PF7/2007-2013) under grant agreement no. 249241 and from the Chief Scientist of the Israeli Ministry of Health under grant agreement no. 3-00000-6356.



Dr Gal-Mor is a molecular microbiologist and head of the Infectious Diseases Research Laboratory at the Sheba Medical Center, Tel-Hashomer, Israel. His primary research interests include microbial pathogenicity and Salmonella virulence and epidemiology.

Table A1

List of the examined Salmonella enterica serovar Infantis isolates, showing source, isolation date, PFGE pattern, and antimicrobial drug susceptibility test results, Israel*
Strain no.SourceIsolation datePFGE patternSusceptibility
852–490Poultry1997 Sep 19I23nal,sxt
62376Clinical (stool)2000 Oct 24I22nal, fd, tet, sxt
90731Clinical (stool)2004 Apr 25I4S
91050Clinical (stool)2004 Apr 25I4S
90205Clinical (stool)2004 May 5I4S
90206Clinical (stool)2004 May 12I4S
90497Clinical (stool)2004 Jun 3I2amp, rox, ctr, cf, fd, sxt
90498Clinical (stool)2004 Jun 3I2amp, fep, ctr, cf, fd, rox, nn
3228Food2004 Jun 13I3fd
90849Clinical (stool)2004 Jun 21I7nal, fd, tet, sxt
91044Clinical (stool)2004 Jul 19I2fd
91377Clinical (stool)2004 Aug 4I2fd
95286Poultry2005 Mar 28I21fd
97258Food2005 Aug 22I3fd
107008Clinical (stool)2007 Jan 8I5fd, tet
107195Clinical (stool)2007 Jan 15I1nal, fd, tet, sxt
107682Clinical (stool)2007 Feb 15I1nal, fd, tet
112303Poultry2007 Nov 8I9nal, fd, tet
113264Poultry2007 Dec 12I12nal, fd, tet, sxt
113571Poultry2008 Jan 7I1nal, fd, tet
114035Poultry2008 Jan 29I1nal, fd, tet
114256Poultry2008 Feb 17I1nal, fd, tet
114509Poultry2008 Mar 9I1nal, fd, tet
115016Poultry2008 Apr 13I8nal,tet
115593Poultry2008 May 18I1nal, fd, tet
115991Poultry2008 Jun 1I1nal, fd, tet
121162Food2008 Sep 8I1nal, fd, tet
118525Poultry2008 Sep 10I14nal, fd, tet
118872Poultry2008 Oct 5I13nal, fd, tet, cf
121056Food2008 Oct 7I1nal, fd, tet, sxt
121061Food2008 Oct 12I1nal, fd, tet
119297Poultry2008 Oct 19I1nal, fd, tet
119305Poultry2008 Oct 26I1nal, fd, tet
121078Food2008 Oct 30I1nal, fd, tet, sxt
121080Food2008 Oct 30I10nal, fd, tet
119491Poultry2008 Nov 2I1nal, fd, tet
119645Clinical (stool)2008 Nov 4I1nal, fd, tet
121093Food2008 Nov 4I1nal, fd, tet
119747Poultry2008 Nov 6I1nal, fd, tet
119944Clinical (stool)2008 Nov 10I1nal, fd, tet
121102Food2008 Nov 10I1nal, fd, tet
120029Clinical (stool)2008 Nov 12I1nal, fd, tet
119815Poultry2008 Nov 16I1nal, fd, tet
121116Food2008 Nov 17I1nal, fd, tet
120309Clinical (stool)2008 Nov 20I1nal, fd, tet
120187Poultry2008 Nov 21I1nal, fd, tet, sxt
120189Poultry2008 Nov 21I1nal, fd, tet
120173Clinical (stool)2008 Nov 24I1nal, fd, tet
120191Poultry2008 Nov 24I1nal, fd, tet, sxt
120186Clinical (stool)2008 Nov 25I1nal, fd, tet
120195Poultry2008 Nov 27I1nal, fd, tet
120089Food2008 Nov 30I1nal, fd, tet
120091Food2008 Nov 30I1nal, fd, tet, sxt
120094Food2008 Nov 30I1nal, fd, tet, sxt
120096Food2008 Nov 30I1nal, fd, tet
120099Food2008 Nov 30I1nal, fd, tet
120100Food2008 Nov 30I11lvx, nal
120101Food2008 Nov 30I1nal, fd, tet
120102Food2008 Nov 30I1nal, fd, tet, sxt
120103Food2008 Nov 30I1nal, fd, tet
120268Clinical (stool)2008 Nov 30I1nal, fd, tet
120314Poultry2008 Nov 30I1nal, fd, tet
120321Poultry2008 Nov 30I1nal, fd, tet
121135Food2008 Dec 1I1nal, fd, tet, sxt
120229Poultry2008 Dec 3I1nal, fd, tet, sxt
120233Poultry2008 Dec 3I1nal, fd, tet
120540Clinical (stool)2008 Dec 3I1nal, fd, tet
121140Food2008 Dec 3I16nal, tet, sxt
120705Clinical (stool)2008 Dec 10I1nal, fd, tet
120895Clinical (stool)2008 Dec 17I6nal, fd, tet
120894Clinical (stool)2008 Dec 18I1nal, fd, tet
120898Clinical (stool)2008 Dec 18I1nal, fd, tet, sxt
113219Poultry2008 Dec 27I1nal, fd, tet
123446Food2009 Jan 13I13nal, fd, tet
121937Poultry2009 Jan 28I1nal, fd, tet
122727Food2009 Mar 9I1nal, fd, tet
123169Clinical (abscess)2009 Apr 3I1nal, fd, tet
122798Poultry2009 Apr 5I1nal, fd, tet
122823Clinical (stool)2009 Apr 7I1nal, fd, tet
123398Clinical (stool)2009 May 3I18nal, fd, tet
123516Poultry2009 May 17I1nal, fd, tet
124182Clinical (blood)2009 May 26I1nal, fd, tet
123787Clinical (wound)2009 Jun 5I1nal, fd, tet, sxt
123844Food2009 Jun 12I1nal, fd, tet
124126Clinical (stool)2009 Jun 17I17nal, fd, tet

*Eighty-seven randomly selected S. enterica ser. Infantis isolates from human, food, and poultry sources were selected for PFGE analysis and antimicrobial drug susceptibility test. Because Salmonella spp. are reportable pathogens in Israel, the strains were submitted to the Government Central Laboratories by various microbiology laboratories throughout Israel. The National Salmonella Reference Center did final serologic identification. Isolate number, their source, isolation date, and PFGE pattern are indicated. Antibacterial drug susceptibility was tested by using the VITEK 1 system (bioMérieux S.A., Marcy l'Etoile, France) and the GNS-210 VITEK card for gram-negative susceptibility testing. Escherichia coli ATTC 25922 was used as a reference strain. The tested antibacterial agents were amoxicillin/clavulanic acid; ampicillin (MIC >32 μg/mL); rox, cefuroxime; cefepime (MIC >32 μg/mL); ceftriaxone (MIC >64 μg/mL); cefuroxime (MIC ≥32 μg/mL); cephalothin (MIC >32 μg/mL); ciprofloxacin; gentamicin; imipenem; levofloxacin (MIC >8 μg/mL); nalidixic acid (MIC >32 μg/mL); nitrofurantoin (MIC >128 μg/mL); piperacillin/tazobactam; tetracycline (MIC >16 μg/mL); tobramycin (MIC >16 μg/mL); and trimethoprim/sulfamethoxazole (MIC range 80–320 μg/mL). PFGE, pulsed-field gel electrophoresis; S, sensitive to all examined antibacterial drugs; nal, nalidixic acid; sxt, trimethoprim/sulfamthoxazole; fd, nitrofurantoin; tet, tetracycline; amp, ampicillin; fep, cefepime; ctr, ceftriaxone; cf, cephalothin; nn, tobramycin; lvx, levofloxacin.
†National Salmonella spp. archive, source unknown.


Suggested citation for this article: Gal-Mor O, Valinsky L, Weinberger M, Guy S, Jaffe J, Ilan Y, et al. Multidrug-resistant Salmonella enterica serovar Infantis, Israel. Emerg Infect Dis [serial on the Internet]. 2010 Nov [date cited]. http://dx.doi.org/10.3201/eid1611.100100


1. Tauxe RV Salmonella Enteritidis and Salmonella Typhimurium: successful subtypes in the modern world. In: Scheld WM, Craig WA, Hughes JM, editors. Emerging infections 4. Washington: American Society for Microbiology; 1999. p. 37–52.
2. Solnik-Isaac H, Weinberger M, Tabak M, Ben-David A, Shachar D, Yaron S Quinolone resistance of Salmonella enterica serovar Virchow isolates from humans and poultry in Israel: evidence for clonal expansion. J Clin Microbiol. 2007;45:2575–9 10.1128/JCM.00062-07 [PMC free article] [PubMed] [Cross Ref]
3. Weinberger M, Keller N Recent trends in the epidemiology of non-typhoid Salmonella and antimicrobial resistance: the Israeli experience and worldwide review. Curr Opin Infect Dis. 2005;18:513–21 10.1097/01.qco.0000186851.33844.b2 [PubMed] [Cross Ref]
4. Weinberger M, Solnik-Isaac H, Shachar D, Reisfeld A, Valinsky L, Andorn N, et al. Salmonella enterica serotype Virchow: epidemiology, resistance patterns and molecular characterisation of an invasive Salmonella serotype in Israel. Clin Microbiol Infect. 2006;12:999–1005 10.1111/j.1469-0691.2006.01466.x [PubMed] [Cross Ref]
5. Fluit AC, Schmitz FJ Class 1 integrons, gene cassettes, mobility, and epidemiology. Eur J Clin Microbiol Infect Dis. 1999;18:761–70 10.1007/s100960050398 [PubMed] [Cross Ref]
6. Hopkins KL, Davies RH, Threlfall EJ Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments. Int J Antimicrob Agents. 2005;25:358–73 10.1016/j.ijantimicag.2005.02.006 [PubMed] [Cross Ref]
7. Gustafson RH Antibiotics use in agriculture: an overview. In: Moats WA, editor. Agricultural uses of antibiotics. Washington: American Chemical Society; 1986. p. 1–6.
8. Nogrady N, Kardos G, Bistyak A, Turcsanyi I, Meszaros J, Galantai Z, et al. Prevalence and characterization of Salmonella Infantis isolates originating from different points of the broiler chicken–human food chain in Hungary. Int J Food Microbiol. 2008;127:162–7 10.1016/j.ijfoodmicro.2008.07.005 [PubMed] [Cross Ref]
9. Nogrady N, Toth A, Kostyak A, Paszti J, Nagy B Emergence of multidrug-resistant clones of Salmonella Infantis in broiler chickens and humans in Hungary. J Antimicrob Chemother. 2007;60:645–8 10.1093/jac/dkm249 [PubMed] [Cross Ref]
10. Shahada F, Sugiyama H, Chuma T, Sueyoshi M, Okamoto K Genetic analysis of multi-drug resistance and the clonal dissemination of beta-lactam resistance in Salmonella Infantis isolated from broilers. Vet Microbiol. 2010;140:136–41 Epub 2009 Jul 10 10.1016/j.vetmic.2009.07.007 [PubMed] [Cross Ref]

Articles from Emerging Infectious Diseases are provided here courtesy of Centers for Disease Control and Prevention
PubReader format: click here to try


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • BioProject
    BioProject links
  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...