Differential expression of outer membrane proteins and quinolone resistance determining region mutations can lead to ciprofloxacin resistance in Salmonella Typhi

Akshay, Sadanand Dangari; Nayak, Srajana; Deekshit, Vijaya Kumar; Rohit, Anusha; Maiti, Biswajit

doi:10.1007/s00203-023-03485-0

Cited by 13 publications

(6 citation statements)

References 58 publications

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“…The upregulation of PSP has been linked to quinolone resistance in E. coli in [ 59 ]. In addition, significant upregulation of outer membrane protein genes is associated with resistance to quinolones in Salmonella Typhi [ 60 ]. This study identifies outer membrane porin, a type of outer membrane protein, as important for nalixidic (quinolone) resistance ( Figure 6 ).…”

Section: Resultsmentioning

confidence: 99%

Predicting Salmonella MIC and Deciphering Genomic Determinants of Antibiotic Resistance and Susceptibility

Ayoola,

Das,

Krishnan

et al. 2024

Microorganisms

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Salmonella spp., a leading cause of foodborne illness, is a formidable global menace due to escalating antimicrobial resistance (AMR). The evaluation of minimum inhibitory concentration (MIC) for antimicrobials is critical for characterizing AMR. The current whole genome sequencing (WGS)-based approaches for predicting MIC are hindered by both computational and feature identification constraints. We propose an innovative methodology called the “Genome Feature Extractor Pipeline” that integrates traditional machine learning (random forest, RF) with deep learning models (multilayer perceptron (MLP) and DeepLift) for WGS-based MIC prediction. We used a dataset from the National Antimicrobial Resistance Monitoring System (NARMS), comprising 4500 assembled genomes of nontyphoidal Salmonella, each annotated with MIC metadata for 15 antibiotics. Our pipeline involves the batch downloading of annotated genomes, the determination of feature importance using RF, Gini-index-based selection of crucial 10-mers, and their expansion to 20-mers. This is followed by an MLP network, with four hidden layers of 1024 neurons each, to predict MIC values. Using DeepLift, key 20-mers and associated genes influencing MIC are identified. The 10 most significant 20-mers for each antibiotic are listed, showcasing our ability to discern genomic features affecting Salmonella MIC prediction with enhanced precision. The methodology replaces binary indicators with k-mer counts, offering a more nuanced analysis. The combination of RF and MLP addresses the limitations of the existing WGS approach, providing a robust and efficient method for predicting MIC values in Salmonella that could potentially be applied to other pathogens.

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Section: Resultsmentioning

confidence: 99%

Predicting Salmonella MIC and Deciphering Genomic Determinants of Antibiotic Resistance and Susceptibility

Ayoola,

Das,

Krishnan

et al. 2024

Microorganisms

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“…Nowadays, multidrug resistance is increasingly becoming a relevant problem in the case of Salmonella species, and several clinical isolates were found to be resistant to fluoroquinolones [ 210 , 211 , 212 , 213 , 214 , 215 ]. Ceftriaxone and azithromycin currently represent the secondary drugs of choice for treating patients suffering from typhus when fluoroquinolone-resistant strains are detected.…”

Section: Gram-negative Bacteriamentioning

confidence: 99%

Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps

et al. 2023

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The number of multidrug-resistant bacteria is rapidly spreading worldwide. Among the various mechanisms determining resistance to antimicrobial agents, multidrug efflux pumps play a noteworthy role because they export extraneous and noxious substrates from the inside to the outside environment of the bacterial cell contributing to multidrug resistance (MDR) and, consequently, to the failure of anti-infective therapies. The expression of multidrug efflux pumps can be under the control of transcriptional regulators and two-component systems (TCS). TCS are a major mechanism by which microorganisms sense and reply to external and/or intramembrane stimuli by coordinating the expression of genes involved not only in pathogenic pathways but also in antibiotic resistance. In this review, we describe the influence of TCS on multidrug efflux pump expression and activity in some Gram-negative and Gram-positive bacteria. Taking into account the strict correlation between TCS and multidrug efflux pumps, the development of drugs targeting TCS, alone or together with already discovered efflux pump inhibitors, may represent a beneficial strategy to contribute to the fight against growing antibiotic resistance.

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“…Selective porins are the efficient components of Salmonella that activate the host’s innate immune responses . Pathogenic bacteria such as S. Typhi, Pseudomonas , Klebsiella , etc., with the assistance of genetic modification in the porin expression in response to antibiotics, have developed key survival strategies. , S. Typhi expresses various porins, of which OmpC and OmpF are major porins expressed constitutively, while OmpS1 and OmpS2 are the main OMPs expressed at low levels. These expressing porins of S. Typhi are highly immunogenic antigens when the exogenous adjuvants are absent in the response .…”

Section: Outer Membrane Proteins and Antibiotic Resistance In Salmonellamentioning

confidence: 99%

“…There are a variety of drug resistance mechanisms, including inactivation of the drug, modification of the target, efflux of the antibiotics, and decrease in membrane permeability . Reduction in membrane permeability is the leading cause of MDR to XDR in S. Typhi. , The antibiotics with a molecular weight (MW) around 600 Da can breach the outer membrane (OM) of Gram-negative organisms. In contrast, other drugs such as vancomycin (1449 Da) and daptomycin (1620 Da) have a MW above 1000 Da and have to pass through the bacterial cell wall through outer membrane proteins (OMPs) .…”

Section: Introductionmentioning

confidence: 99%

Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy

Akshay,

Deekshit,

Mohan Raj

et al. 2023

ACS Infect. Dis.

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Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One such WHO-critical group pathogen is Salmonella. The extensive and inappropriate treatments for Salmonella infections have led from multi-drug resistance (MDR) to extensive drug resistance (XDR). The synergy between efflux-mediated systems and outer membrane proteins (OMPs) may favor MDR in Salmonella. Differential expression of the efflux system and OMPs (influx) and positional mutations are the factors that can be correlated to the development of drug resistance. Insights into the mechanism of influx and efflux of antibiotics can aid in developing a structurally stable molecule that can be proficient at escaping from the resistance loops in Salmonella. Understanding the strategic responsibilities and developing policies to address the surge of drug resistance at the national, regional, and global levels are the needs of the hour. In this Review, we attempt to aggregate all the available research findings and delineate the resistance mechanisms by dissecting the involvement of OMPs and efflux systems. Integrating major OMPs and the efflux system’s differential expression and positional mutation in Salmonella may provide insight into developing strategic therapies for one health application.

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Differential expression of outer membrane proteins and quinolone resistance determining region mutations can lead to ciprofloxacin resistance in Salmonella Typhi

Cited by 13 publications

References 58 publications

Predicting Salmonella MIC and Deciphering Genomic Determinants of Antibiotic Resistance and Susceptibility

Predicting Salmonella MIC and Deciphering Genomic Determinants of Antibiotic Resistance and Susceptibility

Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps

Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy

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