scholarly journals Long-Term Dissemination of CTX-M-5-Producing Hypermutable Salmonella enterica Serovar Typhimurium Sequence Type 328 Strains in Russia, Belarus, and Kazakhstan

2014 ◽  
Vol 58 (9) ◽  
pp. 5202-5210 ◽  
Author(s):  
Varvara K. Kozyreva ◽  
Elena N. Ilina ◽  
Maja V. Malakhova ◽  
Alessandra Carattoli ◽  
Ilya S. Azizov ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Genetic Relatedness ◽  
Single Point ◽  
Point Mutations ◽  
Sequence Type ◽  
Quinolone Resistance ◽  
Resistance Mutations ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTIn this paper, we present evidence of long-term circulation of cefotaxime-resistant clonally relatedSalmonella entericaserovar Typhimurium strains over a broad geographic area. The genetic relatedness of 88 isolates collected from multiple outbreaks and sporadic cases of nosocomial salmonellosis in various parts of Russia, Belarus, and Kazakhstan from 1996 to 2009 was established by multilocus tandem-repeat analysis (MLVA) and multilocus sequence typing (MLST). The isolates belong to sequence type 328 (ST328) and produce CTX-M-5 β-lactamase, whose gene is carried by highly related non-self-conjugative but mobilizable plasmids. Resistance to nalidixic acid and low-level resistance to ciprofloxacin is present in 37 (42%) of the isolates and in all cases is determined by various single point mutations in thegyrAgene quinolone resistance-determining region (QRDR). Isolates of the described clonal group exhibit a hypermutable phenotype that probably facilitates independent acquisition of quinolone resistance mutations.

scholarly journals Characterization of mcr-5-Harboring Salmonella enterica subsp. enterica Serovar Typhimurium Isolates from Animal and Food Origin in Germany

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Maria Borowiak ◽  
Jens A. Hammerl ◽  
Carlus Deneke ◽  
Jennie Fischer ◽  
Istvan Szabo ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Mobile Genetic Elements ◽  
Sequence Type ◽  
Content Type ◽  
Genetic Elements ◽  
Bacterial Chromosomes ◽  
Serovar Typhimurium

ABSTRACT We characterized eight mcr-5-positive Salmonella enterica subsp. enterica serovar Typhimurium sequence type 34 (ST34) isolates obtained from pigs and meat in Germany. Five plasmid types were identified harboring mcr-5 on Tn6452 or putative mobile insertion cassettes. The mobility of mcr-5 was confirmed by integration of Tn6452 into the bacterial chromosomes of two strains and the detection of conjugative mcr-5 plasmids. The association with mobile genetic elements might further enhance mcr-5 distribution.

scholarly journals Emergence of Multidrug-Resistant Salmonella enterica Serovar Goldcoast Strains in Taiwan and International Spread of the ST358 Clone

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Ying-Shu Liao ◽  
Bo-Han Chen ◽  
Yu-Ping Hong ◽  
Ru-Hsiou Teng ◽  
You-Wun Wang ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Genetic Relatedness ◽  
The United States ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Content Type ◽  
The United Kingdom ◽  
Routine Surveillance ◽  
Antimicrobial Resistance Genes ◽  
High Degree

ABSTRACT Salmonella enterica serovar Goldcoast infection was rare in Taiwan; it was not detected in routine surveillance from 2004 to 2013. This serovar was first identified in 2014, but the frequency of infection remained low until 2017. From 2014 to 2016, all but one isolate was pan-susceptible. S. Goldcoast infections abruptly increased in 2018, and all isolates were multidrug-resistant (MDR). All MDR isolates harbored an IncHI2 plasmid, and the majority carried 14 antimicrobial resistance genes, aac(3)-IId, aadA22, aph(3′)-Ia, aph(6)-Id, blaTEM-1B, blaCTX-M-55, lnu(F), floR, qnrS13, arr-2, sul2, sul3, tet(A), and dfrA14. S. Goldcoast strains recovered in Taiwan and 96 of 99 strains from Germany, the Netherlands, the United Kingdom, and the United States belonged to sequence type 358 (ST358). Whole-genome single-nucleotide polymorphism and core genome multilocus sequence type analyses revealed that all strains of the ST358 clone shared a high degree of genetic relatedness. The present study highlighted that a dramatic increase in S. Goldcoast infections followed the emergence of MDR strains and indicated that a genetically closely related S. Goldcoast ST358 clone may have widespread significance internationally.

scholarly journals Molecular Basis of Resistance to Selected Antimicrobial Agents in the Emerging Zoonotic Pathogen Streptococcus suis

2015 ◽  
Vol 53 (7) ◽  
pp. 2332-2336 ◽  
Author(s):  
Mamata Gurung ◽  
Migma Dorji Tamang ◽  
Dong Chan Moon ◽  
Su-Ran Kim ◽  
Jin-Ha Jeong ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Antimicrobial Agents ◽  
Single Point ◽  
Point Mutations ◽  
Streptococcus Suis ◽  
Quinolone Resistance ◽  
Content Type ◽  
Zoonotic Pathogen ◽  
Single Point Mutations

Characterization of 227Streptococcus suisstrains isolated from pigs during 2010 to 2013 showed high levels of resistance to clindamycin (95.6%), tilmicosin (94.7%), tylosin (93.8%), oxytetracycline (89.4%), chlortetracycline (86.8%), tiamulin (72.7%), neomycin (70.0%), enrofloxacin (56.4%), penicillin (56.4%), ceftiofur (55.9%), and gentamicin (55.1%). Resistance to tetracyclines, macrolides, aminoglycosides, and fluoroquinolone was attributed to thetetgene,erm(B),erm(C),mph(C), andmef(A) and/ormef(E) genes,aph(3′)-IIIaandaac(6′)-Ie-aph(2″)-Iagenes, and single point mutations in the quinolone resistance-determining region of ParC and GyrA, respectively.

scholarly journals Increasing Prevalence of Quinolone Resistance in Human Nontyphoid Salmonella enterica Isolates Obtained in Spain from 1981 to 2003

2004 ◽  
Vol 48 (10) ◽  
pp. 3789-3793 ◽  
Author(s):  
José M. Marimón ◽  
María Gomáriz ◽  
Carmen Zigorraga ◽  
Gustavo Cilla ◽  
Emilio Pérez-Trallero
Keyword(s):  
Nalidixic Acid ◽  
Point Mutation ◽  
Salmonella Enterica ◽  
Single Point ◽  
Point Mutations ◽  
Fluoroquinolone Resistance ◽  
Human Consumption ◽  
Single Point Mutation ◽  
Gene Coding ◽  
Serovar Typhimurium

ABSTRACT From January 1981 to December 2003, susceptibility to nalidixic acid was tested in 10,504 nontyphoid Salmonella enterica isolates from patients with acute enteric disease in Gipuzkoa, Spain. The prevalence of nalidixic acid resistance steadily increased from less than 0.5% before 1991 to 38.5% in 2003, mainly due to the increase in resistance among isolates of the most prevalent serovar, S. enterica serovar Enteritidis. For nalidixic acid-resistant isolates, the ciprofloxacin MIC was eightfold higher than that for susceptible isolates, and the nalidixic acid-resistant isolates contained a single point mutation in the gyrA gene (at codons for Ser83 or Asp87). The same mutations were found in a sample of nalidixic acid-resistant nontyphoid Salmonella strains isolated between 1999 and 2003 from retail food for human consumption. In 2003, we identified five S. enterica serovar Typhimurium clinical isolates with high-level fluoroquinolone resistance (ciprofloxacin MIC, 16 μg/ml) with two point mutations in the gyrA gene (coding for Ser83→Phe and Asp87→Asn) and one point mutation in the parC gene (coding for Ser80→Arg). Strict sanitary controls are needed to avoid the spread of ciprofloxacin-resistant serovar Typhimurium isolates, and a more efficient veterinary policy must be adopted to decrease the large burden of Salmonella serovar Enteritidis infections in humans in our region.

scholarly journals HDQ, a Potent Inhibitor of Plasmodium falciparum Proliferation, Binds to the Quinone Reduction Site of the Cytochromebc1Complex

2012 ◽  
Vol 56 (7) ◽  
pp. 3739-3747 ◽  
Author(s):  
Cindy Vallières ◽  
Nicholas Fisher ◽  
Thomas Antoine ◽  
Mohammed Al-Helal ◽  
Paul Stocks ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Potent Inhibitor ◽  
Single Point ◽  
Point Mutations ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Inner Mitochondrial Membrane ◽  
Content Type ◽  
Quinone Reduction ◽  
Inhibitor Resistance

ABSTRACTThe mitochondrialbc1complex is a multisubunit enzyme that catalyzes the transfer of electrons from ubiquinol to cytochromeccoupled to the vectorial translocation of protons across the inner mitochondrial membrane. The complex contains two distinct quinone-binding sites, the quinol oxidation site of thebc1complex (Qo) and the quinone reduction site (Qi), located on opposite sides of the membrane within cytochromeb. Inhibitors of the Qosite such as atovaquone, active against thebc1complex ofPlasmodium falciparum, have been developed and formulated as antimalarial drugs. Unfortunately, single point mutations in the Qosite can rapidly render atovaquone ineffective. The development of drugs that could circumvent cross-resistance with atovaquone is needed. Here, we report on the mode of action of a potent inhibitor ofP. falciparumproliferation, 1-hydroxy-2-dodecyl-4(1H)quinolone (HDQ). We show that the parasitebc1complex—from both control and atovaquone-resistant strains—is inhibited by submicromolar concentrations of HDQ, indicating that the two drugs have different targets within the complex. The binding site of HDQ was then determined by using a yeast model. Introduction of point mutations into the Qisite, namely, G33A, H204Y, M221Q, and K228M, markedly decreased HDQ inhibition. In contrast, known inhibitor resistance mutations at the Qosite did not cause HDQ resistance. This study, using HDQ as a proof-of-principle inhibitor, indicates that the Qisite of thebc1complex is a viable target for antimalarial drug development.

scholarly journals Efficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Michael Frahm ◽  
Sebastian Felgner ◽  
Dino Kocijancic ◽  
Manfred Rohde ◽  
Michael Hensel ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Tumor Targeting ◽  
Antitumor Effect ◽  
Treatment Options ◽  
Tumor Therapy ◽  
Therapeutic Benefit ◽  
Industrialized Countries ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Therapeutic Molecules

ABSTRACTIncreasing numbers of cancer cases generate a great urge for new treatment options. Applying bacteria likeSalmonella entericaserovar Typhimurium for cancer therapy represents an intensively explored option. These bacteria have been shown not only to colonize solid tumors but also to exhibit an intrinsic antitumor effect. In addition, they could serve as tumor-targeting vectors for therapeutic molecules. However, the pathogenicS. Typhimurium strains used for tumor therapy need to be attenuated for safe application. Here, lipopolysaccharide (LPS) deletion mutants (ΔrfaL, ΔrfaG, ΔrfaH, ΔrfaD, ΔrfaP, and ΔmsbBmutants) ofSalmonellawere investigated for efficiency in tumor therapy. Of such variants, the ΔrfaDand ΔrfaGdeep rough mutants exhibited the best tumor specificity and lowest pathogenicity. However, the intrinsic antitumor effect was found to be weak. To overcome this limitation, conditional attenuation was tested by complementing the mutants with an inducible arabinose promoter. The chromosomal integration of the respective LPS biosynthesis genes into thearaBADlocus exhibited the best balance of attenuation and therapeutic benefit. Thus, the present study establishes a basis for the development of an applicably cancer therapeutic bacterium.IMPORTANCECancer has become the second most frequent cause of death in industrialized countries. This and the drawbacks of routine therapies generate an urgent need for novel treatment options. Applying appropriately modifiedS. Typhimurium for therapy represents the major challenge of bacterium-mediated tumor therapy. In the present study, we demonstrated thatSalmonellabacteria conditionally modified in their LPS phenotype exhibit a safe tumor-targeting phenotype. Moreover, they could represent a suitable vehicle to shuttle therapeutic compounds directly into cancerous tissue without harming the host.

scholarly journals OXA-48 Carbapenemase-Producing Salmonella enterica Serovar Kentucky Isolate of Sequence Type 198 in a Patient Transferred from Libya to Switzerland

2014 ◽  
Vol 58 (4) ◽  
pp. 2446-2449 ◽  
Author(s):  
Salome N. Seiffert ◽  
Vincent Perreten ◽  
Sönke Johannes ◽  
Sara Droz ◽  
Thomas Bodmer ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Salmonella Enterica ◽  
Sequence Type ◽  
Content Type ◽  
Screening Strategies

ABSTRACTHere, we report a case of OXA-48-producingSalmonella entericaserovar Kentucky of sequence type 198 (ST198) from perianal screening cultures of a patient transferred from Libya to Switzerland. TheblaOXA-48gene was carried by Tn1999.2and located on an ∼60-kb IncL/M plasmid. ThisSalmonellastrain also possessed theblaVEB-8,aac(6)-Ib,tet(A),sul1, andmphAresistance genes and substitutions in GyrA (Ser83Phe and Asp87Asn) and ParC (Ser80Ile). This finding emphasizes that prompt screening strategies are essential to prevent the dissemination of carbapenemase producers imported from countries where they are endemic.

scholarly journals An Intramolecular Salt Bridge in Bacillus thuringiensis Cry4Ba Toxin Is Involved in the Stability of Helix α-3, Which Is Needed for Oligomerization and Insecticidal Activity

2017 ◽  
Vol 83 (20) ◽  
Author(s):  
Sabino Pacheco ◽  
Isabel Gómez ◽  
Jorge Sánchez ◽  
Blanca-Ines García-Gómez ◽  
Mario Soberón ◽  
...  
Keyword(s):  
Bacillus Thuringiensis ◽  
Double Point ◽  
Single Point ◽  
Three Dimensional ◽  
Point Mutations ◽  
Salt Bridge ◽  
Dimensional Structure ◽  
Cry Toxins ◽  
Content Type ◽  
Domain I

ABSTRACT Bacillus thuringiensis three-domain Cry toxins kill insects by forming pores in the apical membrane of larval midgut cells. Oligomerization of the toxin is an important step for pore formation. Domain I helix α-3 participates in toxin oligomerization. Here we identify an intramolecular salt bridge within helix α-3 of Cry4Ba (D111-K115) that is conserved in many members of the family of three-domain Cry toxins. Single point mutations such as D111K or K115D resulted in proteins severely affected in toxicity. These mutants were also altered in oligomerization, and the mutant K115D was more sensitive to protease digestion. The double point mutant with reversed charges, D111K-K115D, recovered both oligomerization and toxicity, suggesting that this salt bridge is highly important for conservation of the structure of helix α-3 and necessary to promote the correct oligomerization of the toxin. IMPORTANCE Domain I has been shown to be involved in oligomerization through helix α-3 in different Cry toxins, and mutations affecting oligomerization also elicit changes in toxicity. The three-dimensional structure of the Cry4Ba toxin reveals an intramolecular salt bridge in helix α-3 of domain I. Mutations that disrupt this salt bridge resulted in changes in Cry4Ba oligomerization and toxicity, while a double point reciprocal mutation that restored the salt bridge resulted in recovery of toxin oligomerization and toxicity. These data highlight the role of oligomer formation as a key step in Cry4Ba toxicity.

scholarly journals Whole-Genome Sequence of Salmonella enterica subsp. enterica Serovar Typhimurium Strain UPM 260, Isolated from a Broiler Chicken in Perak, Malaysia

2017 ◽  
Vol 5 (46) ◽  
Author(s):  
Najwa Syahirah Roslan ◽  
Shagufta Jabeen ◽  
Nurulfiza Mat Isa ◽  
Abdul Rahman Omar ◽  
Mohd Hair Bejo ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Salmonella Enterica ◽  
Broiler Chicken ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Typhimurium Strain ◽  
Serovar Typhimurium

ABSTRACT Salmonella enterica subsp. enterica serovar Typhimurium is one of several well-categorized Salmonella serotypes recognized globally. Here, we report the whole-genome sequence of S. Typhimurium strain UPM 260, isolated from a broiler chicken.

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