Abstract
Salmonella enterica subsp. enterica (Salmonella), one of the most common causes of bacterial foodborne infections, causes salmonellosis, which is usually self-limiting. However, immunocompromised individuals and children often require antimicrobial therapy. The first line of treatment includes fluoroquinolones, to which Salmonella has emerging resistance worldwide. In fact, the WHO classified fluoroquinolone-resistant Salmonella as a high-priority pathogen. Salmonella carrying genes such as blaCTX and blaCMY can show resistance to cephalosporins which are also regularly used for treatment. This study focused on determining the antimicrobial resistance of 373 Salmonella isolates, collected from various foods, humans, and animals, as well as the environmental sludge between 2005 and 2020 in Türkiye. Phenotypic analysis of the resistance was determined by disk diffusion method. Isolates resistant to any of the following: ciprofloxacin, pefloxacin, azithromycin, and ceftriaxone were tested for the presence of quinolone, beta-lactamase, and/or macrolide resistance genes by PCR and gel electrophoresis. Five multi-drug-resistant isolates were then further whole genome sequenced and analyzed. More than 32% (n = 120) of the isolates showed resistance to fluoroquinolones by disc diffusion. A significant number of quinolone-resistant isolates are presented with mutated parC and gyrA. Furthermore, 42% (n = 106) of the isolates were resistant to azithromycin and 10% of them harbored mphA gene. On the bright side, only eight isolates showed resistance to ceftriaxone. Overall, we observed an increase in the number of isolates showing resistance to fluoroquinolones and azithromycin over the years and low resistance to ceftriaxone.
Similar content being viewed by others
Data Availability
Not applicable.
Code Availability
Not applicable.
References
EFSA (2018) The European Union summary report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2017. EFSA J. https://doi.org/10.2903/j.efsa.2018.5500
Percival SL, Yates M V., Williams DW, et al (2013) Microbiology of Waterborne Diseases: Microbiological Aspects and Risks: Second Edition. Microbiol Waterborne Dis Microbiol Asp Risks Second Ed 1–695. https://doi.org/10.1016/C2010-0-67101-X
Levantesi C, Bonadonna L, Briancesco R et al (2012) Salmonella in surface and drinking water: occurrence and water-mediated transmission. Food Res Int 45:587–602. https://doi.org/10.1016/J.FOODRES.2011.06.037
Monack DM (2012) Salmonella persistence and transmission strategies. Curr Opin Microbiol 15:100–107. https://doi.org/10.1016/J.MIB.2011.10.013
CDC (2018) Outbreaks Involving Salmonella | CDC. In: CDC. https://www.cdc.gov/salmonella/outbreaks.html. Accessed 30 Nov 2021
Eng SK, Pusparajah P, Ab Mutalib NS et al (2015) Salmonella: A review on pathogenesis, epidemiology and antibiotic resistance. Front Life Sci 8:284–293. https://doi.org/10.1080/21553769.2015.1051243
World Health Organization (2005) The treatment of diarrhoea: a manual for physicians and other senior health workers, 4th rev
Teunis PFM (2022) Dose response for Salmonella Typhimurium and Enteritidis and other nontyphoid enteric salmonellae. Epidemics 41:100653. https://doi.org/10.1016/j.epidem.2022.100653
EFSA (2022) The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2019–2020. EFSA J. https://doi.org/10.2903/j.efsa.2022.7209
Palma E, Tilocca B, Roncada P (2020) Antimicrobial Resistance in veterinary medicine: an overview. Int J Mol Sci 21:1914
Medalla F, Gu W, Friedman CR et al (2021) Increased incidence of antimicrobial-resistant nontyphoidal salmonella infections, United States, 2004–2016. Emerg Infect Dis 27:1662–1672. https://doi.org/10.3201/eid2706.204486
Mølbak K (2004) Spread of resistant bacteria and resistance genes from animals to humans—the public health consequences. J Vet Med Ser B 51:364–369. https://doi.org/10.1111/J.1439-0450.2004.00788.X
CDC (2013) Antibiotic Resistance Threats in the United States. Centers DiseasCDC (2013) Antibiot Resist Threat United States Centers Dis Control Prev https//www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdfe Control Prev
Al-Mashhadani M, Hewson R, Vivancos R et al (2011) Foreign travel and decreased ciprofloxacin susceptibility in salmonella enterica infections. Emerg Infect Dis 17:123. https://doi.org/10.3201/EID1701.100999
CDC (2015) National Antimicrobial Resistance Monitoring System NARMS 2015 Human Isolates Surveillance Report
Clark TW, Daneshvar C, Pareek M et al (2010) Enteric fever in a UK regional infectious diseases unit: a 10 year retrospective review. J Infect 60:91–98. https://doi.org/10.1016/J.JINF.2009.11.009
Wen SCH, Best E, Nourse C (2017) Non-typhoidal Salmonella infections in children: review of literature and recommendations for management. J Paediatr Child Health 53:936–941. https://doi.org/10.1111/JPC.13585
Batchelor M, Hopkins K, Threlfall EJ et al (2005) blaCTX-M genes in clinical salmonella isolates recovered from humans in england and wales from 1992 to 2003. Antimicrob Agents Chemother 49:1319. https://doi.org/10.1128/AAC.49.4.1319-1322.2005
Tate H, Folster JP, Hsu CH et al (2017) Comparative analysis of extended-spectrum-β-lactamase CTX-M-65-producing Salmonella enterica serovar infantis isolates from humans, food animals, and retail chickens in the United States. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.00488-17
Pribul BR, Festivo ML, de Souza MMS, dos Prazeres RD (2016) Characterization of quinolone resistance in Salmonella spp. isolates from food products and human samples in Brazil. Braz J Microbiol 47:196–201. https://doi.org/10.1016/J.BJM.2015.04.001
Lin D, Chen K, Wai-Chi Chan E, Chen S (2015) Increasing prevalence of ciprofloxacin-resistant food-borne Salmonella strains harboring multiple PMQR elements but not target gene mutations. Sci Rep 51(5):1–8. https://doi.org/10.1038/srep14754
Wong MHY, Chen S (2013) First detection of oqxAB in Salmonella spp. isolated from food. Antimicrob Agents Chemother 57:658. https://doi.org/10.1128/AAC.01144-12
Faccone D, Lucero C, Albornoz E et al (2018) Emergence of azithromycin resistance mediated by the mph (A) gene in Salmonella Typhimurium clinical isolates in Latin America. J Glob Antimicrob Resist 13:237–239. https://doi.org/10.1016/j.jgar.2018.04.011
Wang J, Li Y, Xu X et al (2017) Antimicrobial resistance of Salmonella enterica serovar Typhimurium in Shanghai China. Front Microbiol 1:1. https://doi.org/10.3389/fmicb.2017.00510
Durul B, Acar S, Bulut E et al (2015) Subtyping of Salmonella food isolates suggests the geographic clustering of serotype telaviv. Foodborne Pathog Dis 12:958–965. https://doi.org/10.1089/fpd.2015.1995
Acar S, Bulut E, Durul B et al (2017) Phenotyping and genetic characterization of Salmonella enterica isolates from Turkey revealing arise of different features specific to geography. Int J Food Microbiol 241:98–107. https://doi.org/10.1016/j.ijfoodmicro.2016.09.031
Cesur A, Sö U, Soyer Y (2019) Isolation and molecular characterization of Salmonellaenterica and Escherichiacolifrom poultry samples. Turkish J Vet Anim Sci 43:408–422. https://doi.org/10.3906/vet-1812-36
Hauser E, Hebner F, Tietze E et al (2011) Diversity of Salmonella enterica serovar derby isolated from pig, pork and humans in Germany. Int J Food Microbiol 151:141–149. https://doi.org/10.1016/j.ijfoodmicro.2011.08.020
Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120. https://doi.org/10.1093/BIOINFORMATICS/BTU170
Bankevich A, Nurk S, Antipov D et al (2012) SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19:455. https://doi.org/10.1089/CMB.2012.0021
Gurevich A, Saveliev V, Vyahhi N, Tesler G (2013) QUAST: quality assessment tool for genome assemblies. Bioinformatics 29:1072–1075. https://doi.org/10.1093/BIOINFORMATICS/BTT086
Yoshida CE, Kruczkiewicz P, Laing CR et al (2016) The Salmonella in silico typing resource (SISTR): an open web-accessible tool for rapidly typing and subtyping draft Salmonella genome assemblies. PloS one. https://doi.org/10.1371/JOURNAL.PONE.0147101
Zhang S, Yin Y, Jones MB et al (2015) Salmonella serotype determination utilizing high-throughput genome sequencing data. J Clin Microbiol 53:1685–1692. https://doi.org/10.1128/JCM.00323-15
Carattoli A, Zankari E, Garciá-Fernández A et al (2014) In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 58:3895–3903. https://doi.org/10.1128/AAC.02412-14
Jia B, Raphenya AR, Alcock B et al (2017) CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res 45:D566–D573. https://doi.org/10.1093/NAR/GKW1004
Cuypers WL, Jacobs J, Wong V et al (2018) Fluoroquinolone resistance in Salmonella: insights by whole genome sequencing. Microb Genomics. https://doi.org/10.1099/mgen.0.000195
EFSA (2017) The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2015. EFSA J. https://doi.org/10.2903/j.efsa.2017.4694
Ryan MP, Dillon C, Adley CC (2011) Nalidixic acid-resistant strains of Salmonella showing decreased susceptibility to fluoroquinolones in the midwestern region of the republic of ireland due to mutations in the gyrA gene. J Clin Microbiol 49:2077. https://doi.org/10.1128/JCM.02574-10
EFSA (2021) The European Union One Health 2019 Zoonoses Report. EFSA J. https://doi.org/10.2903/j.efsa.2021.6406
Kovats RS, Edwards SJ, Hajat S et al (2004) The effect of temperature on food poisoning: a time-series analysis of salmonellosis in ten European countries. Epidemiol Infect 132:443–453. https://doi.org/10.1017/S0950268804001992
Renuka K, Kapil A, Kabra SK et al (2004) Reduced susceptibility to ciprofloxacin and gyrA gene mutation in north indian strains of Salmonella enterica serotype Typhi and serotype Paratyphi A. Microb Drug Resist 10:146–153. https://doi.org/10.1089/1076629041310028
Campioni F, Souza RA, Martins VV et al (2017) Prevalence of gyrA mutations in nalidixic acid-resistant strains of Salmonella enteritidis isolated from humans, food, chickens, and the farm environment in Brazil. Microb Drug Resist 23:421–428. https://doi.org/10.1089/MDR.2016.0024/ASSET/IMAGES/LARGE/FIGURE2.JPEG
Lee HY, Su LH, Tsai MH et al (2009) High rate of reduced susceptibility to ciprofloxacin and ceftriaxone among nontyphoid Salmonella clinical isolates in Asia. Antimicrob Agents Chemother 53:2696–2699. https://doi.org/10.1128/AAC.01297-08
Yildirmak T, Yazgan A, Ozcengiz G (1998) Multiple drug resistance patterns and plasmid profiles of non-typhi Salmonellae in Turkey. Epidemiol Infect 121:303–307. https://doi.org/10.1017/S0950268898001253
Ramachandran A, Shanthi M, Sekar U (2017) Detection of blaCTX-M extended spectrum beta-lactamase producing Salmonella enterica serotype typhi in a tertiary care centre. J Clin Diagn Res 11:21. https://doi.org/10.7860/JCDR/2017/30150.10637
Collignon PJ, McEwen SA (2019) One health—its importance in helping to better control antimicrobial resistance. Trop Med Infect Dis. https://doi.org/10.3390/TROPICALMED4010022
Watkins LF, Karp B, Folster J et al (2017) Emerging azithromycin resistance among nontyphoidal Salmonella isolates in the United States. Open Forum Infect Dis 4:S245–S246. https://doi.org/10.1093/ofid/ofx163.527
Khan S, Kurup P, Vinod V et al (2013) Reconsidering azithromycin disc diffusion interpretive criteria for Salmonellae in view of azithromycin MIC creep among typhoidal and nontyphoidal Salmonella. J Lab Phys. https://doi.org/10.4103/JLP.JLP_99_18
Erdem B, Ercis S, Hascelik G et al (2005) Antimicrobial resistance patterns and serotype distribution among Salmonella enterica strains in Turkey, 2000–2002. Eur J Clin Microbiol Infect Dis 24:220–225. https://doi.org/10.1007/s10096-005-1293-y
Ghoddusi A, Nayeri Fasaei B, Karimi V et al (2015) Molecular identification of Salmonella infantis isolated from backyard chickens and detection of their resistance genes by PCR. Iran J Vet Res 16:293–297
Pavelquesi SLS, de Oliveira Ferreira ACA, Rodrigues ARM et al (2021) Presence of tetracycline and sulfonamide resistance genes in Salmonella spp.: literature review. Antibiotics 10:1314. https://doi.org/10.3390/antibiotics10111314
Acknowledgements
The authors gratefully acknowledge the Middle East Technical University, Scientific Research Projects BAP for funding the project GAP-314-2020-10285.
Funding
This study was funded by the Middle East Technical University, Scientific Research Projects BAP, project number: GAP-314-2020-10285.
Author information
Authors and Affiliations
Contributions
DK contributed to investigation, data analysis and visualization, and writing of the original draft; MG contributed to conceptualization, investigation, methodology, and writing, reviewing, and editing of the manuscript; YS contributed to conceptualization, funding acquisition, project administration, supervision, and writing, reviewing, and editing of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
This paper is part of a thesis and has not been published before and it is not under consideration by any other journal at the same time. All the authors approve the manuscript submission to this journal and none of the authors have any conflicting interests.
Ethical Approval
Not applicable.
Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Konyali, D., Guzel, M. & Soyer, Y. Genomic Characterization of Salmonella enterica Resistant to Cephalosporin, Quinolones, And Macrolides. Curr Microbiol 80, 344 (2023). https://doi.org/10.1007/s00284-023-03458-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00284-023-03458-y