scholarly journals A soxRS-Constitutive Mutation Contributing to Antibiotic Resistance in a Clinical Isolate of Salmonella enterica (Serovar Typhimurium)

2001 ◽  
Vol 45 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Anastasia Koutsolioutsou ◽  
Elizabeth A. Martins ◽  
D. G. White ◽  
S. B. Levy ◽  
Bruce Demple
Keyword(s):  
Antibiotic Resistance ◽  
Salmonella Enterica ◽  
Constitutive Expression ◽  
Laboratory Strain ◽  
Quinolone Resistance ◽  
Clinical Strain ◽  
Enteropathogenic Bacteria ◽  
Development Of Resistance ◽  
Serovar Typhimurium ◽  
Constitutive Mutation

ABSTRACT The soxRS regulon is activated by redox-cycling drugs such as paraquat and by nitric oxide. The >15 genes of this system provide resistance to both oxidants and multiple antibiotics. An association between clinical quinolone resistance and elevated expression of the soxRS regulon has been observed inEscherichia coli, but this association has not been explored for other enteropathogenic bacteria. Here we describe asoxRS-constitutive mutation in a clinical strain ofSalmonella enterica (serovar Typhimurium) that arose with the development of resistance to quinolones during treatment. The elevated quinolone resistance in this strain derived from a point mutation in the soxR gene and could be suppressed intrans by multicopy wild-type soxRS. Multiple-antibiotic resistance was also transferred to a laboratory strain of S. enterica by introducing the cloned mutantsoxR gene from the clinical strain. The results show that constitutive expression of soxRS can contribute to antibiotic resistance in clinically relevant S. enterica.

scholarly journals Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

2014 ◽  
Vol 58 (11) ◽  
pp. 6528-6535 ◽  
Author(s):  
Nicolás F. Cordeiro ◽  
José A. Chabalgoity ◽  
Lucía Yim ◽  
Rafael Vignoli
Keyword(s):  
Growth Rate ◽  
Antibiotic Resistance ◽  
Epithelial Cells ◽  
Salmonella Enterica ◽  
Virulent Strain ◽  
Constitutive Expression ◽  
Fitness Cost ◽  
Resistant Bacteria ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTAntibiotic resistance, especially due to β-lactamases, has become one of the main obstacles in the correct treatment ofSalmonellainfections; furthermore, antibiotic resistance determines a gain of function that may encompass a biological cost, or fitness reduction, to the resistant bacteria. The aim of this work was to determinein vitroif the production of the class B β-lactamase VIM-2 determined a fitness cost forSalmonella entericaserovar Typhimurium. To that end the geneblaVIM-2was cloned into the virulent strainS. Typhimurium SL1344, using both the tightly regulated pBAD22 vector and the natural plasmid pST12, for inducible and constitutive expression, respectively. Fitness studies were performed by means of motility, growth rate, invasiveness in epithelial cells, and plasmid stability. The expression ofblaVIM-2was accompanied by alterations in micro- and macroscopic morphology and reduced growth rate and motility, as well as diminished invasiveness in epithelial cells. These results suggest that VIM-2 production entails a substantial fitness cost forS. Typhimurium, which in turn may account for the extremely low number of reports of metallo-β-lactamase-producingSalmonellaspp.

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

2004 ◽  
Vol 48 (10) ◽  
pp. 3729-3735 ◽  
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.

scholarly journals Understanding the basis of antibiotic resistance: a platform for drug discovery

Microbiology ◽  
2014 ◽  
Vol 160 (11) ◽  
pp. 2366-2373 ◽  
Author(s):  
Laura J. V. Piddock
Keyword(s):  
Antibiotic Resistance ◽  
Salmonella Enterica ◽  
Efflux Pump ◽  
Antibiotic Resistance Genes ◽  
Multi Drug Resistance ◽  
Annual Conference ◽  
Altered Expression ◽  
Genetic Inactivation ◽  
Fluoroquinolone Antibiotics ◽  
Serovar Typhimurium

There are numerous genes in Salmonella enterica serovar Typhimurium that can confer resistance to fluoroquinolone antibiotics, including those that encode topoisomerase proteins, the primary targets of this class of drugs. However, resistance is often multifactorial in clinical isolates and it is not uncommon to also detect mutations in genes that affect the expression of proteins involved in permeability and multi-drug efflux. The latter mechanism, mediated by tripartite efflux systems, such as that formed by the AcrAB–TolC system, confers inherent resistance to many antibiotics, detergents and biocides. Genetic inactivation of efflux genes gives multi-drug hyper-susceptibility, and in the absence of an intact AcrAB–TolC system some chromosomal and transmissible antibiotic resistance genes no longer confer clinically relevant levels of resistance. Furthermore, a functional multi-drug resistance efflux pump, such as AcrAB–TolC, is required for virulence and the ability to form a biofilm. In part, this is due to altered expression of virulence and biofilm genes being sensitive to efflux status. Efflux pump expression can be increased, usually due to mutations in regulatory genes, and this confers resistance to clinically useful drugs such as fluoroquinolones and β-lactams. Here, I discuss some of the work my team has carried out characterizing the mechanisms of antibiotic resistance in Salmonella enterica serovar Typhimurium from the late 1980s to 2014. A video of this Prize Lecture, presented at the Society for General Microbiology Annual Conference 2014, can be viewed via this link: https://www.youtube.com/watch?v=MCRumMV99Yw.

scholarly journals Assessment of Antibiotic Resistance Phenotype and Integrons in Salmonella enterica serovar Typhimurium Isolated from Swine

2008 ◽  
Vol 70 (10) ◽  
pp. 1133-1137 ◽  
Author(s):  
Nabin RAYAMAJHI ◽  
Sang Gyun KANG ◽  
Mi Lan KANG ◽  
Hee Soo LEE ◽  
Kyung Yoon PARK ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Resistance Phenotype ◽  
Serovar Typhimurium

scholarly journals Alterations of Salmonella enterica Serovar Typhimurium Antibiotic Resistance under Environmental Pressure

2018 ◽  
Vol 84 (19) ◽  
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.

scholarly journals A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to Salmonella enterica Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells

2020 ◽  
Vol 8 (5) ◽  
pp. 630
Author(s):  
Vanesa García ◽  
Ana Herrero-Fresno ◽  
Rosaura Rodicio ◽  
Alfonso Felipe-López ◽  
Ignacio Montero ◽  
...  
Keyword(s):  
Iron Content ◽  
Salmonella Enterica ◽  
Iron Uptake ◽  
Type Strain ◽  
Wild Type Strain ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Iron Acquisition ◽  
Clinical Strain ◽  
Wild Type ◽  
Serovar Typhimurium

The resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of Salmonella enterica serovar Typhimurium recovered in Spain and other European countries. pUO-StVR2 carries several genes encoding a FetMP-Fls system, which could be involved in iron uptake. We therefore analyzed S. Typhimurium LSP 146/02, a clinical strain selected as representative of the isolates carrying the plasmid, and an otherwise isogenic mutant lacking four genes (fetMP-flsDA) of the fetMP-fls region. Growth curves and determination of the intracellular iron content under iron-restricted conditions demonstrated that deletion of these genes impairs iron acquisition. Thus, under these conditions, the mutant grew significantly worse than the wild-type strain, its iron content was significantly lower, and it was outcompeted by the wild-type strain in competition assays. Importantly, the strain lacking the fetMP-flsDA genes was less invasive in cultured epithelial HeLa cells and replicated poorly upon infection of RAW264.7 macrophages. The genes were introduced into S. Typhimurium ATCC 14028, which lacks the FetMP-Fls system, and this resulted in increased growth under iron limitation as well as an increased ability to multiply inside macrophages. These findings indicate that the FetMP-Fls iron acquisition system exceeds the benefits conferred by the other high-affinity iron uptake systems carried by ATCC 14028 and LSP 146/02. We proposed that effective iron acquisition by this system in conjunction with antimicrobial resistance encoded from the same plasmid have greatly contributed to the epidemic success of S. Typhimurium isolates harboring pUO-StVR2.

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