The ancient small mobilizable plasmid pALWED1.8 harboring a new variant of the non-cassette streptomycin/spectinomycin resistance gene aadA27

Plasmid ◽  
2016 ◽  
Vol 84-85 ◽  
pp. 36-43 ◽  
Author(s):  
Anton Kurakov ◽  
Sofia Mindlin ◽  
Alexey Beletsky ◽  
Natalya Shcherbatova ◽  
Andrey Rakitin ◽  
...  
Keyword(s):  
Resistance Gene ◽  
Spectinomycin Resistance ◽  
Mobilizable Plasmid ◽  
New Variant

scholarly journals Mechanistic Insights into Crosstalk of Tet(X) and MCR-1, Two Resistance Enzymes Co-produced by A Single Plasmid

2020 ◽  
Author(s):  
Yongchang Xu ◽  
Lizhang Liu ◽  
Huimin Zhang ◽  
Youjun Feng
Keyword(s):  
Resistance Gene ◽  
Infection Model ◽  
Global Public Health ◽  
Genetic Determinants ◽  
Colistin Resistance ◽  
E Coli ◽  
New Variant ◽  
Single Plasmid

AbstractTigecycline and colistin are few of last-resort defenses used in anti-infection therapies against carbapenem-resistant bacterial pathogens. The successive emergence of plasmid-borne tet(X) tigecycline resistance mechanism and mobile colistin resistance (mcr) determinant, renders them clinically ineffective, posing a risky challenge to global public health. Here, we report that co-carriage of tet(X6) and mcr-1 gives co-resistance to both classes of antibiotics by a single plasmid in E. coli. Genomic analysis suggested that transposal transfer of mcr-1 proceeds into the plasmid pMS8345A, in which a new variant tet(X6) is neighbored with Class I integron. The structure-guided mutagenesis finely revealed the genetic determinants of Tet(X6) in the context of phenotypic tigecycline resistance. The combined evidence in vitro and in vivo demonstrated its enzymatic action of Tet(X6) in the destruction of tigecycline. The presence of Tet(X6) (and/or MCR-1) robustly prevents the accumulation of reactive oxygen species (ROS) induced by tigecycline (and/or colistin). Unlike that mcr-1 exerts fitness cost in E. coli, tet(X6) does not. In the tet(X6)-positive strain that co-harbors mcr-1, tigecycline resistance is independently of colistin resistance caused by MCR-1-mediated lipid A remodeling, and vice versa. Co-production of Tet(X6) and MCR-1 gives no synergistic delayed growth of the recipient E. coli. Similar to that MCR-1 behaves in the infection model of G. mellonella, Tet(X6) renders the treatment of tigecycline ineffective. Therefore, co-transfer of such two AMR genes is of great concern in the context of “one health” comprising environmental/animal/human sectors, and heightened efforts are required to monitor its dissemination.Author summaryWe report that tet(X6), a new tigecycline resistance gene, is co-carried with the other resistance gene mcr-1 by a single plasmid. Not only have we finely mapped genetic determinants of tet(X6), but also revealed its biochemical action of tigecycline destruction. Crosstalk of Tet(X6) with MCR-1 is addressed. Tet(X6) tigecycline resistance is independently of MCR-1 colistin resistance, and vice versa. Similar to MCR-1 that renders colistin clinically ineffective, Tet(X6) leads to the failure of tigecycline treatment in the infection model of G. mellonella. This study extends mechanistic understanding mechanism and interplay of Tet(X6) and MCR-1, coproduced by a single plasmid. It also heightens the need to prevent rapid and large-scaled spread of AMR.

scholarly journals New Gene Cassettes for Trimethoprim Resistance,dfr13, and Streptomycin-Spectinomycin Resistance,aadA4, Inserted on a Class 1 Integron

2000 ◽  
Vol 44 (2) ◽  
pp. 355-361 ◽  
Author(s):  
Peter V. Adrian ◽  
Christopher J. Thomson ◽  
Keith P. Klugman ◽  
Sebastian G. B. Amyes
Keyword(s):  
Resistance Gene ◽  
Dihydrofolate Reductase ◽  
Antibiotic Resistance Genes ◽  
Amino Acid Identity ◽  
Aminoglycoside Resistance ◽  
Class 1 Integron ◽  
Spectinomycin Resistance ◽  
Class 1 ◽  
Dihydrofolate Reductases ◽  
A Site

ABSTRACT In a previous survey of 357 trimethoprim-resistant isolates of aerobic gram-negative bacteria from commensal fecal flora, hybridization experiments showed that 25% (90 of 357) of the isolates failed to hybridize to specific oligonucleotide probes for dihydrofolate reductase types 1, 2b, 3, 5, 6, 7, 8, 9, 10, and 12. Subsequent cloning and sequencing of a plasmid-borne trimethoprim resistance gene from one of these isolates revealed a new dihydrofolate reductase gene, dfr13, which occurred as a cassette integrated in a site-specific manner in a class 1 integron. The gene product shared 84% amino acid identity with dfr12 and exhibited a trimethoprim inhibition profile similar to that ofdfr12. Gene probing experiments with an oligonucleotide probe specific for this gene showed that 12.3% (44 of 357) of the isolates which did not hybridize to probes for other dihydrofolate reductases hybridized to this probe. Immediately downstream ofdfr13, a new cassette, an aminoglycoside resistance gene of the class AADA [ANT(3")(9)-I], which encodes streptomycin-spectinomycin resistance, was identified. This gene shares 57% identity with the consensus aadA1(ant(3")-Ia) and has been called aadA4(ant(3")-Id). The 3′ end of the aadA4 cassette was truncated by IS26, which was contiguous with a truncated form of Tn3. On the same plasmid, pUK2381, a second copy of IS26 was associated with sul2, which suggests that both integrase and transposase activities have played major roles in the arrangement and dissemination of antibiotic resistance genesdfr13, aadA4, bla TEM-1, and sul2.

scholarly journals Versatile nourseothricin and streptomycin/spectinomycin resistance gene cassettes and their use in chromosome integration vectors

2016 ◽  
Vol 129 ◽  
pp. 8-13
Author(s):  
Stephanie S. Lehman ◽  
Katherine M. Mladinich ◽  
Angkana Boonyakanog ◽  
Takehiko Mima ◽  
RoxAnn R. Karkhoff-Schweizer ◽  
...  
Keyword(s):  
Resistance Gene ◽  
Spectinomycin Resistance ◽  
Gene Cassettes

scholarly journals A Novel aadA Aminoglycoside Resistance Gene in Bovine and Porcine Pathogens

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Andrew Cameron ◽  
Cassidy L. Klima ◽  
Reuben Ha ◽  
Robert J. Gruninger ◽  
Rahat Zaheer ◽  
...  
Keyword(s):  
Resistance Gene ◽  
Resistance Genes ◽  
Pathogen Detection ◽  
Animal Species ◽  
Mobile Element ◽  
Streptomycin Resistance ◽  
Human Pathogens ◽  
Aminoglycoside Resistance ◽  
Multiple Production ◽  
New Variant

Aminoglycosides are important antimicrobials used worldwide for prophylaxis and/or therapy in multiple production animal species. The emergence of new resistance genes jeopardizes current pathogen detection and treatment methods. The risk of resistance gene transfer to other animal and human pathogens is elevated when resistance genes are carried by mobile genetic elements. This study identified a new variant of a spectinomycin/streptomycin resistance gene harbored in a self-transmissible mobile element. The gene was also present in four different bovine pathogen species.

scholarly journals Salmonella Genomic Island 1 Multidrug Resistance Gene Clusters in Salmonella enterica Serovar Agona Isolated in Belgium in 1992 to 2002

2004 ◽  
Vol 48 (7) ◽  
pp. 2510-2517 ◽  
Author(s):  
Benoît Doublet ◽  
Patrick Butaye ◽  
Hein Imberechts ◽  
David Boyd ◽  
Michael R. Mulvey ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Resistance Gene ◽  
Salmonella Enterica ◽  
Genomic Island ◽  
Gene Clusters ◽  
Complex Class ◽  
Class 1 Integron ◽  
Transposase Gene ◽  
New Variant ◽  
Class 1

ABSTRACT Salmonella genomic island 1 (SGI1) harbors a multidrug resistance (MDR) gene cluster which is a complex class 1 integron. Variant SGI1 MDR gene clusters conferring different MDR profiles have also been identified in several Salmonella enterica serovars and classified as SGI1-A to -F. A retrospective study was undertaken to characterize MDR regions from serovar Agona strains harboring SGI1 isolated from poultry in Belgium between 1992 and 2002. A total of 171 serovar Agona strains, displaying resistance to at least one antibiotic, were studied for the presence of SGI1. SGI1 was detected in 94 serovar Agona strains. The most prevalent variant was SGI1-A (85%), which harbors within the SGI1 complex class 1 integron a common region (CR1) containing orf513, a putative transposase gene, adjacent to the dfrA10 trimethoprim resistance gene. A new variant SGI1 named SGI1-G was identified in two strains. It consisted of the pse-1 gene cassette, as in SGI1-B, but with additional insertion of the orf513/dfrA10 region structure. Seven strains displaying the typical SGI1 MDR profile (Ap Cm Ff Sm Sp Su Tc) showed genetic variation at the 3′ end of SGI1. These strains harbored the insertion of the CR1 containing orf513 as in SGI1-A, -D, and -G. However, downstream the right end of CR1, they presented different 7.4- to 8.5-kb deletions of the SGI1 3′ end that extended to the chromosomal genes yieE and yieF. These results suggest a possible role of CR1 in deletion formation, as has been reported for some insertion sequences. Pulsed-field gel electrophoresis analysis showed that all the serovar Agona SGI1-carrying strains belonged to a single clone. Thus, SGI1 is largely encountered in serovar Agona strains isolated from poultry in Belgium, the most prevalent variant being SGI1-A. SGI1 MDR region undergoes recombinational events resulting in a diversity of MDR gene clusters.

scholarly journals A New Evolutionary Variant of the Streptogramin A Resistance Protein, Vga(A)LC, from Staphylococcus haemolyticus with Shifted Substrate Specificity towards Lincosamides

2006 ◽  
Vol 50 (12) ◽  
pp. 4070-4076 ◽  
Author(s):  
G. Novotna ◽  
J. Janata
Keyword(s):  
Amino Acid ◽  
Substrate Specificity ◽  
Resistance Gene ◽  
Atp Binding ◽  
Amino Acid Substitutions ◽  
Abc Proteins ◽  
Susceptible Host ◽  
Staphylococcus Haemolyticus ◽  
New Variant ◽  
Transport Experiment

ABSTRACT We found a new variant of the streptogramin A resistance gene, vga(A)LC, in clinical isolates of Staphylococcus haemolyticus resistant to lincomycin and clindamycin but susceptible to erythromycin and in which no relevant lincosamide resistance gene was detected. The gene vga(A)LC, differing from the gene vga(A) at the protein level by seven amino acid substitutions, was present exclusively in S. haemolyticus strains resistant to both lincosamides and streptogramin A (LSA phenotype). Antibiotic resistance profiles of the ATP-binding cassette (ABC) proteins Vga(A)LC and Vga(A) in the antibiotic-susceptible host S. aureus RN4220 were compared. It was shown that Vga(A)LC conferred resistance to both lincosamides and streptogramin A, while Vga(A) conferred significant resistance to streptogramin A only. Detailed analysis of the seven amino acid substitutions, distinguishing the two related ABC proteins with different substrate specificities, identified the substrate-recognizing site: four clustered substitutions (L212S, G219V, A220T, and G226S) in the spacer between the two ATP-binding cassettes altered the substrate specificity and constituted the lincosamide-streptogramin A resistance phenotype. A transport experiment with radiolabeled lincomycin demonstrated that the mechanism of lincosamide resistance in S. haemolyticus was identical to that of the reported macrolide-streptogramin B resistance conferred by Msr(A).

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