Characterization of Variant Salmonella Genomic Island 1 Multidrug Resistance Regions from Serovars Typhimurium DT104 and Agona

ABSTRACT Strains of multidrug-resistant Salmonella enterica serovar Typhimurium DT104 (DT104) and S. enterica serovar Agona (Agona) have been found to harbor Salmonella genomic island 1 (SGI1), a 43-kb genomic region that contains many of the drug resistance genes. Such strains are resistant to ampicillin (pse-1), chloramphenicol/florfenicol (floR), streptomycin/spectinomycin (aadA2), sulfonamides (sul1), and tetracycline [tet(G)] (commonly called the ACSSuT phenotype). All five resistance genes are found in a 13-kb multidrug resistance (MDR) region consisting of an unusual class I integron structure related to In4. We examined DT104 and Agona strains that exhibited other resistance phenotypes to determine if the resistance genes were associated with variant SGI1 MDR regions. All strains were found to harbor variant SGI1-like elements by using a combination of Southern hybridization, PCR mapping, and sequencing. Variant SGI1-like elements were found with MDR regions consisting of (i) an integron consisting of the SGI1 MDR region with the addition of a region containing a putative transposase gene (orf513) and dfrA10 located between duplicated qacEΔ1/sulI genes (SGI1-A; ACSSuTTm); (ii) an integron with either an aadA2 (SSu) or a pse-1 (ASu) cassette (SGI1-C and SGI1-B, respectively); (iii) an integron consisting of the SGI1-C MDR region plus an orf513/dfrA10 region as in SGI1-A (SGI1-D; ASSuTm; ampicillin resistance due to a TEM β-lactamase); and (iv) an integron related to that in SGI1 but which contains a 10-kb inversion between two copies of IS6100, one which is inserted in floR (SGI1-E; ASSuT). We hypothesize that the MDR of SGI1 is subject to recombinational events that lead to the various resistance phenotypes in the Salmonella strains in which it is found.

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Antibiotic Resistance Genes and Salmonella Genomic Island 1 in Salmonella enterica Serovar Typhimurium Isolated in Italy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.9.2821-2828.2002 ◽

2002 ◽

Vol 46 (9) ◽

pp. 2821-2828 ◽

Cited By ~ 55

Author(s):

Alessandra Carattoli ◽

Emma Filetici ◽

Laura Villa ◽

Anna Maria Dionisi ◽

Antonia Ricci ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Salmonella Enterica ◽

Genomic Island ◽

Antibiotic Resistance Genes ◽

Tetracycline Resistance ◽

Gene Cassette ◽

Multidrug Resistant ◽

Phage Types ◽

Serovar Typhimurium

ABSTRACT Fifty-four epidemiologically unrelated multidrug-resistant Salmonella enterica serovar Typhimurium isolates, collected between 1992 and 2000 in Italy, were analyzed for the presence of integrons. Strains were also tested for Salmonella genomic island 1 (SGI1), carrying antibiotic resistance genes in DT104 strains. A complete SGI1 was found in the majority of the DT104 strains. Two DT104 strains, showing resistance to streptomycin-spectinomycin and sulfonamides, carried a partially deleted SGI1 lacking the flost , tetR, and tetA genes, conferring chloramphenicol-florfenicol and tetracycline resistance, and the integron harboring the pse-1 gene cassette, conferring ampicillin resistance. The presence of SGI1 was also observed in serovar Typhimurium strains belonging to other phage types, suggesting either the potential mobility of this genomic island or changes in the phage-related phenotype of DT104 strains.

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Whole-Genome Analysis ofSalmonella entericaSerovar Typhimurium T000240 Reveals the Acquisition of a Genomic Island Involved in Multidrug Resistance via IS1Derivatives on the Chromosome

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01215-10 ◽

2010 ◽

Vol 55 (2) ◽

pp. 623-630 ◽

Cited By ~ 32

Author(s):

Hidemasa Izumiya ◽

Tsuyoshi Sekizuka ◽

Hideo Nakaya ◽

Masumi Taguchi ◽

Akio Oguchi ◽

...

Keyword(s):

Multidrug Resistance ◽

Gene Transfer ◽

Horizontal Gene Transfer ◽

Genome Analysis ◽

Genomic Island ◽

Whole Genome ◽

Class 1 Integron ◽

Serovar Typhimurium ◽

Class 1

ABSTRACTSalmonella entericaserovar Typhimurium is frequently associated with life-threatening systemic infections, and the recent global emergence of multidrug resistance inS. entericaisolates from agricultural and clinical settings has raised concerns. In this study, we determined the whole-genome sequence of fluoroquinolone-resistantS. entericaserovar Typhimurium T000240 strain (DT12) isolated from human gastroenteritis in 2000. Comparative genome analysis revealed that T000240 displays high sequence similarity to strain LT2, which was originally isolated in 1940, indicating that progeny of LT2 might be reemerging. T000240 possesses a unique 82-kb genomic island, designated as GI-DT12, which is composed of multidrug resistance determinants, including a Tn2670-like composite transposon (class 1 integron [intI1,blaoxa-30,aadA1,qacEΔ1, andsul1], mercury resistance proteins, and chloramphenicol acetyltransferase), a Tn10-like tetracycline resistance protein (tetA), the aerobactin iron-acquisition siderophore system (lutAandlucABC), and an iron transporter (sitABCD). Since GI-DT12 is flanked by IS1derivatives, IS1-mediated recombination likely played a role in the acquisition of this genomic island through horizontal gene transfer. The aminoglycoside-(3)-N-acetyltransferase (aac(3)) gene and a class 1 integron harboring thedfrA1gene cassette responsible for gentamicin and trimethoprim resistance, respectively, were identified on plasmid pSTMDT12_L and appeared to have been acquired through homologous recombination with IS26. This study represents the first characterization of the unique genomic island GI-DT12 that appears to be associated with possible IS1-mediated recombination inS. entericaserovar Typhimurium. It is expected that future whole-genome studies will aid in the characterization of the horizontal gene transfer events for the emergingS. entericaserovar Typhimurium strains.

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Multidrug Resistance Salmonella Genomic Island 1 in a Morganella morganii subsp. morganii Human Clinical Isolate from France

mSphere ◽

10.1128/msphere.00118-17 ◽

2017 ◽

Vol 2 (2) ◽

Cited By ~ 21

Author(s):

Eliette Schultz ◽

Olivier Barraud ◽

Jean-Yves Madec ◽

Marisa Haenni ◽

Axel Cloeckaert ◽

...

Keyword(s):

Public Health ◽

Multidrug Resistance ◽

Resistance Genes ◽

Salmonella Enterica ◽

Genomic Island ◽

Multidrug Resistant ◽

Health Concern ◽

Human Pathogens ◽

Morganella Morganii ◽

Content Type

ABSTRACT Since its initial identification in epidemic multidrug-resistant Salmonella enterica serovar Typhimurium DT104 strains, several SGI1 variants, SGI1 lineages, and SGI1-related elements (SGI2, PGI1, and AGI1) have been described in many bacterial genera (Salmonella, Proteus, Morganella, Vibrio, Shewanella, etc.). They constitute a family of multidrug resistance site-specific integrative elements acquired by horizontal gene transfer, SGI1 being the best-characterized element. The horizontal transfer of SGI1/PGI1 elements into other genera is of public health concern, notably with regard to the spread of critically important resistance genes such as ESBL and carbapenemase genes. The identification of SGI1 in Morganella morganii raises the issue of (i) the potential for SGI1 to emerge in other human pathogens and (ii) its bacterial host range. Further surveillance and research are needed to understand the epidemiology, the spread, and the importance of the members of this SGI1 family of integrative elements in contributing to antibiotic resistance development. Salmonella genomic island 1 (SGI1) is a multidrug resistance integrative mobilizable element that harbors a great diversity of antimicrobial resistance gene clusters described in numerous Salmonella enterica serovars and also in Proteus mirabilis. A serious threat to public health was revealed in the recent description in P. mirabilis of a SGI1-derivative multidrug resistance island named PGI1 (Proteus genomic island 1) carrying extended-spectrum-β-lactamase (ESBL) and metallo-β-lactamase resistance genes, bla VEB-6 and bla NDM-1, respectively. Here, we report the first description of Salmonella genomic island 1 (SGI1) in a multidrug-resistant clinical Morganella morganii subsp. morganii strain isolated from a patient in France in 2013. Complete-genome sequencing of the strain revealed SGI1 variant SGI1-L carrying resistance genes dfrA15, floR, tetA(G), bla PSE-1 (now referred to as bla CARB-2), and sul1, conferring resistance to trimethoprim, phenicols, tetracyclines, amoxicillin, and sulfonamides, respectively. The SGI1-L variant was integrated into the usual chromosome-specific integration site at the 3′ end of the trmE gene. Beyond Salmonella enterica and Proteus mirabilis, the SGI1 integrative mobilizable element may thus also disseminate its multidrug resistance phenotype in another genus belonging to the Proteae tribe of the family Enterobacteriaceae. IMPORTANCE Since its initial identification in epidemic multidrug-resistant Salmonella enterica serovar Typhimurium DT104 strains, several SGI1 variants, SGI1 lineages, and SGI1-related elements (SGI2, PGI1, and AGI1) have been described in many bacterial genera (Salmonella, Proteus, Morganella, Vibrio, Shewanella, etc.). They constitute a family of multidrug resistance site-specific integrative elements acquired by horizontal gene transfer, SGI1 being the best-characterized element. The horizontal transfer of SGI1/PGI1 elements into other genera is of public health concern, notably with regard to the spread of critically important resistance genes such as ESBL and carbapenemase genes. The identification of SGI1 in Morganella morganii raises the issue of (i) the potential for SGI1 to emerge in other human pathogens and (ii) its bacterial host range. Further surveillance and research are needed to understand the epidemiology, the spread, and the importance of the members of this SGI1 family of integrative elements in contributing to antibiotic resistance development.

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Chromosome-Mediated Multidrug Resistance in Salmonella enterica Serovar Typhi

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04081-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 721-723 ◽

Cited By ~ 15

Author(s):

Chien-Shun Chiou ◽

Munirul Alam ◽

Jung-Che Kuo ◽

Yen-Yi Liu ◽

Pei-Jen Wang

Keyword(s):

Multidrug Resistance ◽

Resistance Genes ◽

Salmonella Enterica ◽

Genomic Island ◽

Multidrug Resistant ◽

First Line ◽

Content Type ◽

Salmonella Enterica Serovar Typhi

ABSTRACTA salmonella genomic island, designated SGI11, was found in 18 of 26 multidrug-resistantSalmonella entericaserovar Typhi isolates from Bangladesh. SGI11 was an IS1composite transposon and carried 7 resistance genes that conferred resistance to 5 first-line antimicrobials. Eleven of the 18 SGI11-carryingS. Typhi isolates had developed resistance to high levels of ciprofloxacin.

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AcrAB-TolC Directs Efflux-Mediated Multidrug Resistance in Salmonella enterica Serovar Typhimurium DT104

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.10.3729-3735.2004 ◽

2004 ◽

Vol 48 (10) ◽

pp. 3729-3735 ◽

Cited By ~ 109

Author(s):

Sylvie Baucheron ◽

Shaun Tyler ◽

David Boyd ◽

Michael R. Mulvey ◽

Elisabeth Chaslus-Dancla ◽

...

Keyword(s):

Antibiotic Resistance ◽

Multidrug Resistance ◽

Salmonella Enterica ◽

Genomic Island ◽

Phage Type ◽

Efflux Pumps ◽

Multidrug Resistant ◽

Quinolone Resistance ◽

Efflux System ◽

Serovar Typhimurium

ABSTRACT Multidrug-resistant Salmonella enterica serovar Typhimurium definitive phage type 104 (DT104) strains harbor a genomic island, called Salmonella genomic island 1 (SGI1), which contains an antibiotic resistance gene cluster conferring resistance to ampicillin, chloramphenicol, florfenicol, streptomycin, sulfonamides, and tetracyclines. They may be additionally resistant to quinolones. Among the antibiotic resistance genes there are two, i.e., floR and tet(G), which code for efflux pumps of the major facilitator superfamily with 12 transmembrane segments that confer resistance to chloramphenicol-florfenicol and the tetracyclines, respectively. In the present study we determined, by constructing acrB and tolC mutants, the role of the AcrAB-TolC multidrug efflux system in the multidrug resistance of several DT104 strains displaying additional quinolone resistance or not displaying quinolone resistance. This study shows that the quinolone resistance and the decreased fluoroquinolone susceptibilities of the strains are highly dependent on the AcrAB-TolC efflux system and that single mutations in the quinolone resistance-determining region of gyrA are of little relevance in mediating this resistance. Overproduction of the AcrAB efflux pump, as determined by Western blotting with an anti-AcrA polyclonal antibody, appeared to be the major mechanism of resistance to quinolones. Moreover, chloramphenicol-florfenicol and tetracycline resistance also appeared to be highly dependent on the presence of AcrAB-TolC, since the introduction of mutations in the respective acrB and tolC genes resulted in a susceptible or intermediate resistance phenotype, according to clinical MIC breakpoints, despite the presence of the FloR and Tet(G) efflux pumps. Resistance to other antibiotics, ampicillin, streptomycin, and sulfonamides, was not affected in the acrB and tolC mutants of DT104 strains harboring SGI1. Therefore, AcrAB-TolC appears to direct efflux-mediated resistance to quinolones, chloramphenicol-florfenicol, and tetracyclines in multidrug-resistant S. enterica serovar Typhimurium DT104 strains.

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Genomic Characterization of A Multidrug-resistant Citrobacter freundii Strain ZT01-0079 Co-Producing blaNDM-1 and blaSHV-12 using MiSeq and MinION

10.21203/rs.3.rs-92305/v1 ◽

2020 ◽

Author(s):

Tingyan Zhang ◽

Yanfeng Lin ◽

Zhonghong Li ◽

Xiong Liu ◽

Jinhui Li ◽

...

Keyword(s):

Resistance Genes ◽

Southern Blotting ◽

Multiple Drug Resistance ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Multiple Drug ◽

Citrobacter Freundii ◽

Rapid Spread ◽

Genomic Characterization

Abstract Background: The emergence of multi-drug resistant Citrobacter freundii poses daunting challenges to the treatment of clinical infections. The purpose of this study was to characterize the genome of a C. freundii strain with an IncX3 plasmid encoding both the blaNDM-1 and blaSHV-12 genes.Methods: Strain ZT01-0079 was isolated from a clinical urine sample. The Vitek2 system was used for identification and antimicrobial susceptibility testing. The presence of blaNDM-1 was detected by PCR and sequencing. Conjugation experiments and Southern blotting were performed to determine the transferability of the blaNDM-1- carrying plasmid. Nanopore and Illumina sequencing were performed to better understand the genomic characteristics of the strain.Results: Strain ZT01-0079 was identified as C. freundii, and the coexistence of blaNDM-1 and multiple drug resistance genes was confirmed. Electrophoresis and Southern blotting showed that blaNDM-1 was located on a ~53kb IncX3 plasmid. The NDM-1-encoding plasmid was successfully transferred at a frequency of 1.68×10−3. Both blaNDM-1 and blaSHV-12 were located on the self-transferable IncX3 plasmid.Conclusion: The rapid spread of the IncX3 plasmid highlights the importance of continuous monitoring of the prevalence of NDM-1-encoding Enterobacteriaceae. Mutations of existing carbapenem resistance genes will bring formidable challenges to clinical treatment.

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Salmonella enterica Serovar Typhi Strains Isolated in Korea Containing a Multidrug Resistance Class 1 Integron

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.6.2006-2008.2003 ◽

2003 ◽

Vol 47 (6) ◽

pp. 2006-2008 ◽

Cited By ~ 21

Author(s):

Hyunjoo Pai ◽

Jeong-hum Byeon ◽

Sunmi Yu ◽

Bok Kwon Lee ◽

Shukho Kim

Keyword(s):

Multidrug Resistance ◽

Resistance Genes ◽

Salmonella Enterica ◽

Multidrug Resistant ◽

Conjugative Plasmid ◽

The Novel ◽

Class 1 Integron ◽

Salmonella Enterica Serovar Typhi ◽

Class 1 ◽

Clonal Spread

ABSTRACT Six strains of Salmonella enterica serovar Typhi which were resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, streptomycin, tetracycline, and gentamicin were isolated in Korea. This multidrug resistance was transferred by a conjugative plasmid of about 50 kb. The plasmid harbored a class 1 integron, which included six resistance genes, aacA4b, catB8, aadA1, dfrA1, aac(6′)-IIa, and the novel blaP2, in that order. All of the isolates showed the same-size plasmids and the same ribotyping patterns, which suggests a clonal spread of these multidrug-resistant isolates.

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Alterations of Salmonella enterica Serovar Typhimurium Antibiotic Resistance under Environmental Pressure

Applied and Environmental Microbiology ◽

10.1128/aem.01173-18 ◽

2018 ◽

Vol 84 (19) ◽

Cited By ~ 14

Author(s):

Mengfei Peng ◽

Serajus Salaheen ◽

Robert L. Buchanan ◽

Debabrata Biswas

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Salmonella Enterica ◽

Tetracycline Resistance ◽

Multidrug Resistant ◽

Genetic Alterations ◽

Antibiotic Resistant ◽

Content Type ◽

Farm Systems ◽

Serovar Typhimurium

ABSTRACT Microbial horizontal gene transfer is a continuous process that shapes bacterial genomic adaptation to the environment and the composition of concurrent microbial ecology. This includes the potential impact of synthetic antibiotic utilization in farm animal production on overall antibiotic resistance issues; however, the mechanisms behind the evolution of microbial communities are not fully understood. We explored potential mechanisms by experimentally examining the relatedness of phylogenetic inference between multidrug-resistant Salmonella enterica serovar Typhimurium isolates and pathogenic Salmonella Typhimurium strains based on genome-wide single-nucleotide polymorphism (SNP) comparisons. Antibiotic-resistant S. Typhimurium isolates in a simulated farm environment barely lost their resistance, whereas sensitive S. Typhimurium isolates in soils gradually acquired higher tetracycline resistance under antibiotic pressure and manipulated differential expression of antibiotic-resistant genes. The expeditious development of antibiotic resistance and the ensuing genetic alterations in antimicrobial resistance genes in S. Typhimurium warrant effective actions to control the dissemination of Salmonella antibiotic resistance. IMPORTANCE Antibiotic resistance is attributed to the misuse or overuse of antibiotics in agriculture, and antibiotic resistance genes can also be transferred to bacteria under environmental stress. In this study, we report a unidirectional alteration in antibiotic resistance from susceptibility to increased resistance. Highly sensitive Salmonella enterica serovar Typhimurium isolates from organic farm systems quickly acquired tetracycline resistance under antibiotic pressure in simulated farm soil environments within 2 weeks, with expression of antibiotic resistance-related genes that was significantly upregulated. Conversely, originally resistant S. Typhimurium isolates from conventional farm systems lost little of their resistance when transferred to environments without antibiotic pressure. Additionally, multidrug-resistant S. Typhimurium isolates genetically shared relevancy with pathogenic S. Typhimurium isolates, whereas susceptible isolates clustered with nonpathogenic strains. These results provide detailed discussion and explanation about the genetic alterations and simultaneous acquisition of antibiotic resistance in S. Typhimurium in agricultural environments.

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