Dataset Information

A Race against Time: Reduced Azithromycin Susceptibility in Salmonella enterica Serovar Typhi in Pakistan.

ABSTRACT: Antimicrobial resistance is an ongoing issue in the treatment of typhoid fever. Resistance to first-line antimicrobials and extensively drug resistant (XDR) Salmonella Typhi isolates in Pakistan have left azithromycin as the only remaining effective oral treatment. Here, we report the emergence of organisms with a single point mutation in acrB gene, implicated in azithromycin resistance, in a S. Typhi isolate from Pakistan. The isolation of this organism is worrisome and highlights the significance of the introduction of typhoid conjugate vaccine in South Asia.IMPORTANCE The emergence of XDR Salmonella Typhi in Pakistan has left azithromycin as the only viable oral treatment option. Here, we report the detection of an azithromycin resistance-associated mutation in one S. Typhi isolate. This finding is important because any possible spread of azithromycin resistance in S. Typhi isolates would make it nearly impossible to treat in outpatient settings due to the need of injectable antibiotics. Our findings also signify the importance of introduction of typhoid conjugate vaccine in regions of endemicity such as Pakistan.

SUBMITTER: Iqbal J

PROVIDER: S-EPMC7376502 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

A Race against Time: Reduced Azithromycin Susceptibility in Salmonella enterica Serovar Typhi in Pakistan.

Iqbal Junaid J Dehraj Irum F IF Carey Megan E ME Dyson Zoe A ZA Garrett Denise D Seidman Jessica C JC Kabir Furqan F Saha Senjuti S Baker Stephen S Qamar Farah N FN

mSphere 20200722 4

Antimicrobial resistance is an ongoing issue in the treatment of typhoid fever. Resistance to first-line antimicrobials and extensively drug resistant (XDR) Salmonella Typhi isolates in Pakistan have left azithromycin as the only remaining effective oral treatment. Here, we report the emergence of organisms with a single point mutation in acrB gene, implicated in azithromycin resistance, in a S. Typhi isolate from Pakistan. The isolation of this organism is worrisome and hig ...[more]

PMID: 32699118

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Project description:BackgroundTyphoid fever is an acute systemic infection of humans caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi). In chronic carriers, the bacteria survive the harsh environment of the gallbladder by producing biofilm. The phenotype of S. Typhi biofilm cells is significantly different from the free-swimming planktonic cells, and studies have shown that they are associated with antibiotic resistance, immune system evasion, and bacterial persistence. However, the mechanism of this transition and the events leading to biofilm formation are unknown. High throughput sequencing was performed to identify the genes involved in biofilm formation and to postulate the mechanism of action.ResultsPlanktonic S. Typhi cells were cultured using standard nutrient broth whereas biofilm cells were cultured in a stressful environment using high shearing-force and bile to mimic the gallbladder. Sequencing libraries were prepared from S. Typhi planktonic cells and mature biofilm cells using the Illumina HiSeq 2500 platform, and the transcriptome data obtained were processed using Cufflinks bioinformatics suite of programs to investigate differential gene expression between the two phenotypes. A total of 35 up-regulated and 29 down-regulated genes were identified. The identities of the differentially expressed genes were confirmed using NCBI BLAST and their functions were analyzed. The results showed that the genes associated with metabolic processes and biofilm regulations were down-regulated while those associated with the membrane matrix and antibiotic resistance were highly up-regulated.ConclusionsIt is proposed that the biofilm phenotype of S. Typhi allows the bacteria to increase production of the membrane matrix in order to serve as a physical shield and to adhere to surfaces, and enter an energy conservation state in response to the stressful environment. Conversely, the planktonic phenotype allows the bacteria to produce flagella and increase metabolic activity to enable the bacteria to migrate and form new colonies of infection. This data provide a basis for further studies to uncover the mechanism of biofilm formation in S. Typhi and to discover novel genes or pathways associated with the development of the typhoid carrier state.

Dataset Information

A Race against Time: Reduced Azithromycin Susceptibility in Salmonella enterica Serovar Typhi in Pakistan.

Publications

A Race against Time: Reduced Azithromycin Susceptibility in <i>Salmonella enterica</i> Serovar Typhi in Pakistan.

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