Identification of a ChromosomalShigella flexneriMulti-Antibiotic Resistance Locus Which Shares Sequence and Organizational Similarity with the Resistance Region of the Plasmid NR1

Plasmid ◽  
1997 ◽  
Vol 37 (3) ◽  
pp. 159-168 ◽  
Author(s):  
K. Rajakumar ◽  
D. Bulach ◽  
J. Davies ◽  
L. Ambrose ◽  
C. Sasakawa ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Locus ◽  
Organizational Similarity

scholarly journals Ferric Dicitrate Transport System (Fec) of Shigella flexneri 2a YSH6000 Is Encoded on a Novel Pathogenicity Island Carrying Multiple Antibiotic Resistance Genes

2001 ◽  
Vol 69 (10) ◽  
pp. 6012-6021 ◽  
Author(s):  
Shelley N. Luck ◽  
Sally A. Turner ◽  
Kumar Rajakumar ◽  
Harry Sakellaris ◽  
Ben Adler
Keyword(s):  
Antibiotic Resistance ◽  
Iron Uptake ◽  
Culture Media ◽  
Shigella Flexneri ◽  
Antibiotic Resistance Genes ◽  
Resistance Locus ◽  
Uptake System ◽  
Bacterial Survival ◽  
Multiple Antibiotic Resistance ◽  
Insertional Inactivation

ABSTRACT Iron uptake systems which are critical for bacterial survival and which may play important roles in bacterial virulence are often carried on mobile elements, such as plasmids and pathogenicity islands (PAIs). In the present study, we identified and characterized a ferric dicitrate uptake system (Fec) in Shigella flexneriserotype 2a that is encoded by a novel PAI termed theShigella resistance locus (SRL) PAI. Thefec genes are transcribed in S. flexneri, and complementation of a fec deletion inEscherichia coli demonstrated that they are functional. However, insertional inactivation of fecI, leading to a loss in fec gene expression, did not impair the growth of the parent strain of S. flexneri in iron-limited culture media, suggesting that S. flexneri carries additional iron uptake systems capable of compensating for the loss of Fec-mediated iron uptake. DNA sequence analysis showed that thefec genes are linked to a cluster of multiple antibiotic resistance determinants, designated the SRL, on the chromosome ofS. flexneri 2a. Both the SRL and fec loci are carried on the 66,257-bp SRL PAI, which has integrated into theserX tRNA gene and which carries at least 22 prophage-related open reading frames, including one for a P4-like integrase. This is the first example of a PAI that carries genes encoding antibiotic resistance and the first report of a ferric dicitrate uptake system in Shigella.

scholarly journals Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

2017 ◽  
Vol 114 (5) ◽  
pp. 1075-1080 ◽  
Author(s):  
Sonja Lehtinen ◽  
François Blanquart ◽  
Nicholas J. Croucher ◽  
Paul Turner ◽  
Marc Lipsitch ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Balancing Selection ◽  
Bacterial Species ◽  
Allelic Diversity ◽  
Antibiotic Consumption ◽  
Resistance Locus ◽  
Partial Explanation ◽  
Fitness Advantage ◽  
Long Duration ◽  
Resistant Strains

Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, includingStreptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence of antibiotic sensitive and resistant strains are not fully understood. While allelic diversity can be maintained at a locus by direct balancing selection, there is no evidence for such selection acting in the case of resistance. In this work, we propose a mechanism for maintaining coexistence at the resistance locus: linkage to a second locus that is under balancing selection and that modulates the fitness effect of resistance. We show that duration of carriage plays such a role, with long duration of carriage increasing the fitness advantage gained from resistance. We therefore predict that resistance will be more common in strains with a long duration of carriage and that mechanisms maintaining diversity in duration of carriage will also maintain diversity in antibiotic resistance. We test these predictions inS. pneumoniaeand find that the duration of carriage of a serotype is indeed positively correlated with the prevalence of resistance in that serotype. These findings suggest heterogeneity in duration of carriage is a partial explanation for the coexistence of sensitive and resistant strains and that factors determining bacterial duration of carriage will also affect the prevalence of resistance.

scholarly journals A bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locus

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
J. Andrés Valderrama ◽  
Surashree S. Kulkarni ◽  
Victor Nizet ◽  
Ethan Bier
Keyword(s):  
Antibiotic Resistance ◽  
Copy Number ◽  
Genetic System ◽  
Single Copy ◽  
Drive System ◽  
High Copy Number ◽  
Resistance Locus ◽  
Gene Drive ◽  
Bacterial Gene ◽  
Guide Rna

AbstractGene-drive systems in diploid organisms bias the inheritance of one allele over another. CRISPR-based gene-drive expresses a guide RNA (gRNA) into the genome at the site where the gRNA directs Cas9-mediated cleavage. In the presence of Cas9, the gRNA cassette and any linked cargo sequences are copied via homology-directed repair (HDR) onto the homologous chromosome. Here, we develop an analogous CRISPR-based gene-drive system for the bacterium Escherichia coli that efficiently copies a gRNA cassette and adjacent cargo flanked with sequences homologous to the targeted gRNA/Cas9 cleavage site. This “pro-active” genetic system (Pro-AG) functionally inactivates an antibiotic resistance marker on a high copy number plasmid with ~ 100-fold greater efficiency than control CRISPR-based methods, suggesting an amplifying positive feedback loop due to increasing gRNA dosage. Pro-AG can likewise effectively edit large plasmids or single-copy genomic targets or introduce functional genes, foreshadowing potential applications to biotechnology or biomedicine.

scholarly journals Copy Number of an Integron-Encoded Antibiotic Resistance Locus Regulates a Virulence and Opacity Switch in Acinetobacter baumannii AB5075

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Sarah E. Anderson ◽  
Chui Yoke Chin ◽  
David S. Weiss ◽  
Philip N. Rather
Keyword(s):  
T Cells ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Small Rna ◽  
Copy Number ◽  
Transcriptional Profiling ◽  
Single Copy ◽  
Northern Blotting ◽  
Resistance Locus ◽  
Content Type

ABSTRACT We describe a novel genetic mechanism in which tandem amplification of a plasmid-borne integron regulates virulence, opacity variation, and global gene expression by altering levels of a putative small RNA (sRNA) in Acinetobacter baumannii AB5075. Copy number of this amplified locus correlated with the rate of switching between virulent opaque (VIR-O) and avirulent translucent (AV-T) cells. We found that prototypical VIR-O colonies, which exhibit high levels of switching and visible sectoring with AV-T cells by 24 h of growth, harbor two copies of this locus. However, a subset of opaque colonies that did not form AV-T sectors within 24 h were found to harbor only one copy. The colonies with decreased sectoring to AV-T were designated low-switching opaque (LSO) variants and were found to exhibit a 3-log decrease in switching relative to that of the VIR-O. Overexpression studies revealed that the element regulating switching was localized to the 5′ end of the aadB gene within the amplified locus. Northern blotting indicated that an sRNA of approximately 300 nucleotides (nt) is encoded in this region and is likely responsible for regulating switching to AV-T. Copy number of the ∼300-nt sRNA was also found to affect virulence, as the LSO variant exhibited decreased virulence during murine lung infections. Global transcriptional profiling revealed that >100 genes were differentially expressed between VIR-O and LSO variants, suggesting that the ∼300-nt sRNA may act as a global regulator. Several virulence genes exhibited decreased expression in LSO cells, potentially explaining their decreased virulence. IMPORTANCE Acinetobacter baumannii remains a leading cause of hospital-acquired infections. Widespread multidrug resistance in this species has prompted the WHO to name carbapenem-resistant A. baumannii as its top priority for research and development of new antibiotics. Many strains of A. baumannii undergo a high-frequency virulence switch, which is an attractive target for new therapeutics targeting this pathogen. This study reports a novel mechanism controlling the frequency of switching in strain AB5075. The rate of switching from the virulent opaque (VIR-O) to the avirulent translucent (AV-T) variant is positively influenced by the copy number of an antibiotic resistance locus encoded on a plasmid-borne composite integron. Our data suggest that this locus encodes a small RNA that regulates opacity switching. Low-switching opaque variants, which harbor a single copy of this locus, also exhibit decreased virulence. This study increases our understanding of this critical phenotypic switch, while also identifying potential targets for virulence-based A. baumannii treatments.

scholarly journals Molecular Epidemiology of the SRL Pathogenicity Island

2003 ◽  
Vol 47 (2) ◽  
pp. 727-734 ◽  
Author(s):  
Sally A. Turner ◽  
Shelley N. Luck ◽  
Harry Sakellaris ◽  
Kumar Rajakumar ◽  
Ben Adler
Keyword(s):  
Antibiotic Resistance ◽  
Molecular Epidemiology ◽  
Structural Variation ◽  
Shigella Flexneri ◽  
Pathogenicity Island ◽  
Enteric Pathogens ◽  
The Other ◽  
Resistance Locus ◽  
Multiple Antibiotic Resistance ◽  
Linkage Studies

ABSTRACT The Shigella resistance locus (SRL), which is carried on the SRL pathogenicity island (PAI) in Shigella flexneri 2a YSH6000, mediates resistance to the antibiotics streptomycin, ampicillin, chloramphenicol, and tetracycline. In the present study, we investigated the distribution and structural variation of the SRL and the SRL PAI in 71 Shigella isolates and 28 other enteric pathogens by PCR and Southern analysis. The SRL and SRL-related loci, although absent from the other enteric pathogens evaluated in this study, were found to be present in a number of Shigella isolates. SRL PAI markers were also present in the majority of strains carrying the SRL and SRL-related loci. PCR linkage studies with six of these strains demonstrated that the SRL is carried on elements similar in structure and organization to the YSH6000 SRL PAI, consistent with the hypothesis that the SRL PAI may be involved in the spread of multiple-antibiotic resistance in these strains.

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