Multiple Mechanisms Confer Resistance to Azithromycin in
            <i>Shigella</i>
            in Bangladesh: a Comprehensive Whole Genome-Based Approach

Nusrin, Suraia; Asad, Asaduzzaman; Hayat, Shoma; Islam, Bitali; Begum, Ruma; Nabila, Fahmida Habib; Islam, Zhahirul

doi:10.1128/spectrum.00741-22

Cited by 7 publications

(4 citation statements)

References 56 publications

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“…In the current study, we found sharp increase of AZM-resistance after 2014 and mphA gene was the key mechanism of resistance. Interestingly, in one of our recently published studies, we reported for the rst time of macrolide resistance pKSR100 when the plasmid carrying IS26-mphA-mrx-mphR(A)-IS6100 in Shigella isolated in Bangladesh the years after 2014 47 .…”

Section: Discussionmentioning

confidence: 97%

Increasing trend of antibiotic resistance in Shigella in Bangladesh: a plasmid-mediated transfer of mphA macrolide resistance gene

Asad,

Jahan,

Munni

et al. 2023

Preprint

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Shigellosis remains a common gastrointestinal disease mostly in children <5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.

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Section: Discussionmentioning

confidence: 97%

Increasing trend of antibiotic resistance in Shigella in Bangladesh: a plasmid-mediated transfer of mphA macrolide resistance gene

Asad,

Jahan,

Munni

et al. 2023

Preprint

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“…A IncFII type plasmid pKSR100 is the most crucial genomic entity fostering AZM resistance 35 , 52 . We reported for the first time of macrolide resistance pKSR100 when the plasmid carrying IS26– mph A –mrx–mph R(A)–IS6100 in Shigella isolated in Bangladesh the years after 2014 53 .…”

Section: Discussionmentioning

confidence: 99%

Multidrug-resistant conjugative plasmid carrying mphA confers increased antimicrobial resistance in Shigella

Asad,

Jahan,

Munni

et al. 2024

Sci Rep

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Shigellosis remains a common gastrointestinal disease mostly in children < 5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.

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“…60 In the gene cluster mphA-mrx(A)-mphR(A) for high-level macrolide inactivation, mphA encodes a phosphotransferase that inactivates erythromycin and mrx(A) encodes a protein required for expression of MphA, whereas MphR(A) encoded by mphR(A) negatively regulates the expression of mphA at the transcriptional level. 61 The IS26-mph(A)-mrx(A)-mph(R)(A)-IS6100 unit, which is linked to the global dissemination of macrolideresistance genes, 62 is the most common form in plasmids carrying mphA. 63 Class 1 integrons are prevalent genetic elements that play a key role in the spread of antibiotic resistance, 64 allowing bacteria to capture and exchange ARGs embedded in the gene cassettes.…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing of an Escherichia coli ST69 Strain Harboring blaCTX-M-27 on a Hybrid Plasmid

Wang,

Guan,

Lin

et al. 2024

IDR

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Objective Escherichia coli is a common Gram-negative human pathogen. The emergence of E. coli with multiple-antibiotic-resistant phenotypes has become a serious health concern. This study reports the whole-genome sequences of third-generation cephalosporin-resistant (3GC-R) and multidrug-resistant (MDR) E. coli EC6868 and explores the acquired antibiotic-resistance genes (ARGs) as well as their genetic contexts. Methods E. coli EC6868 was isolated from a vaginal secretion sample of a pregnant patient in China. The antimicrobial susceptibility was assessed, and whole-genome sequencing was conducted. The acquired ARGs, insertion sequence (IS) elements, and integrons within the genome of E. coli EC6868 were identified, and the genetic contexts associated with the ARGs were analyzed systematically. Results E. coli EC6868 was determined to belong to ST69 and harbored a 144.9-kb IncF plasmid (pEC6868-1) with three replicons (Col156, IncFIB AP001918 , and IncFII). The ESBL gene bla CTX-M-27 was located on the structure “∆IS Ecp1 - bla CTX-M-27 -IS 903B ”, which was widely present in the species of Enterobacteriales. Other ARGs carried by plasmid pEC6868-1 were mainly located on the 18.9-kb IS 26 -composite transposon (five copies of intact IS 26 and one copy of truncated IS 26 ) composing of IS 26-mphA-mrx(A)-mphR(A) -IS 6100 , ∆Tn As3-eamA-tet(A)-tetR(A)-aph(6)-Id -a ph(3”)-Ib-sul2- IS 26 , and a class 1 integron, which was widely present on IncF plasmids of E. coli , mainly distributed in ST131, ST38, and ST405. Notably, pEC6868 in our study was the first report on a plasmid harboring the 18.9-kb structure in E. coli ST69 in China. Conclusion The 3GC-R E. coli ST69 strain with an MDR IncF plasmid carrying bla CTX-M-27 and other ARGs, conferring resistance to aminoglycosides, macrolides, sulfonamides, tetracycline, and trimethoprim, was identified in a hospital in China. Mobile genetic elements including IS Ecp1 , IS 903B , IS 26 , Tn 3 , IS 6100 and class 1 integron were found within the MDR region, which could play important roles in the global dissemination of these resistance genes.

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Multiple Mechanisms Confer Resistance to Azithromycin in Shigella in Bangladesh: a Comprehensive Whole Genome-Based Approach

Abstract: Shigella can frequently transform into a superbug due to uncontrolled and rogue administration of antibiotics and the emergence of HGT of antimicrobial resistance factors. The advent of AZM resistance in Shigella has become a serious concern in the treatment of shigellosis.

Cited by 7 publications

References 56 publications

Increasing trend of antibiotic resistance in Shigella in Bangladesh: a plasmid-mediated transfer of mphA macrolide resistance gene

Increasing trend of antibiotic resistance in Shigella in Bangladesh: a plasmid-mediated transfer of mphA macrolide resistance gene

Multidrug-resistant conjugative plasmid carrying mphA confers increased antimicrobial resistance in Shigella

Whole-Genome Sequencing of an Escherichia coli ST69 Strain Harboring blaCTX-M-27 on a Hybrid Plasmid

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