Elucidation of molecular mechanism for colistin resistance among Gram-negative isolates from tertiary care hospitals

Urooj, Maleeha; Ullah, Rooh; Ali, Sakhawat; Mohyuddin, Aisha; Mirza, Hira Mehboob; Faryal, Rani

doi:10.1016/j.jiac.2022.01.002

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…lpxM adds a secondary acyl chain to lipid A, and mutation in lpxM can reduce colistin susceptibility in K. pneumoniae [ 18 ]. The identified mutations in eptA , arnA , arnB , arnT, and kpnF in K. pneumoniae have been reported to increase colistin resistance [ 100 ]. The mutations in arnA , arnB , arnC , arnD , arnF , and arnT modify the LPS.…”

Section: Discussionmentioning

confidence: 99%

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings

Talat,

Khan,

Khan

2024

BMC Microbiol

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Background Colistin is a last-resort antibiotic used in extreme cases of multi-drug resistant (MDR) Gram-negative bacterial infections. Colistin resistance has increased in recent years and often goes undetected due to the inefficiency of predominantly used standard antibiotic susceptibility tests (AST). To address this challenge, we aimed to detect the prevalence of colistin resistance strains through both Vitek®2 and broth micro-dilution. We investigated 1748 blood, tracheal aspirate, and pleural fluid samples from the Intensive Care Unit (ICU), Neonatal Intensive Care Unit (NICU), and Tuberculosis and Respiratory Disease centre (TBRD) in an India hospital. Whole-genome sequencing (WGS) of extremely drug-resitant (XDR) and pan-drug resistant (PDR) strains revealed the resistance mechanisms through the Resistance Gene Identifier (RGI.v6.0.0) and Snippy.v4.6.0. Abricate.v1.0.1, PlasmidFinder.v2.1, MobileElementFinder.v1.0.3 etc. detected virulence factors, and mobile genetic elements associated to uncover the pathogenecity and the role of horizontal gene transfer (HGT). Results This study reveals compelling insights into colistin resistance among global high-risk clinical isolates: Klebsiella pneumoniae ST147 (16/20), Pseudomonas aeruginosa ST235 (3/20), and ST357 (1/20). Vitek®2 found 6 colistin-resistant strains (minimum inhibitory concentrations, MIC = 4 μg/mL), while broth microdilution identified 48 (MIC = 32–128 μg/mL), adhering to CLSI guidelines. Despite the absence of mobile colistin resistance (mcr) genes, mechanisms underlying colistin resistance included mgrB deletion, phosphoethanolamine transferases arnT, eptB, ompA, and mutations in pmrB (T246A, R256G) and eptA (V50L, A135P, I138V, C27F) in K. pneumoniae. P. aeruginosa harbored phosphoethanolamine transferases basS/pmrb, basR, arnA, cprR, cprS, alongside pmrB (G362S), and parS (H398R) mutations. Both strains carried diverse clinically relevant antimicrobial resistance genes (ARGs), including plasmid-mediated blaNDM-5 (K. pneumoniae ST147) and chromosomally mediated blaNDM-1 (P. aeruginosa ST357). Conclusion The global surge in MDR, XDR and PDR bacteria necessitates last-resort antibiotics such as colistin. However, escalating resistance, particularly to colistin, presents a critical challenge. Inefficient colistin resistance detection methods, including Vitek2, alongside limited surveillance resources, accentuate the need for improved strategies. Whole-genome sequencing revealed alarming colistin resistance among K. pneumoniae and P. aeruginosa in an Indian hospital. The identification of XDR and PDR strains underscores urgency for enhanced surveillance and infection control. SNP analysis elucidated resistance mechanisms, highlighting the complexity of combatting resistance.

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Section: Discussionmentioning

confidence: 99%

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings

Talat,

Khan,

Khan

2024

BMC Microbiol

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“…The presence of colistin resistance-conferring eptB gene in the core genome is of grave concern as colistin is the last resort cephalosporin antibiotic and recently, its presence has been reported through PCR-assay in Klebsiella sp. from Pakistan [43]. Urooj et al [43] chose strains that already carried mcr genes.…”

Section: 4pan-genomicsmentioning

confidence: 99%

“…from Pakistan [43]. Urooj et al [43] chose strains that already carried mcr genes. Nucleotide mutation G507A was present in both whole genome sequenced isolates but additionally, one carried C747T and the other A642T, C651T and C933T mutation.…”

Section: 4pan-genomicsmentioning

confidence: 99%

Nanopore sequencing of antibiotic-resistantKlebsiella pneumoniaeJRCGR1 isolate from Pakistan and country scale pan-genomics

Basharat

Nisa

Irfan

et al. 2023

Preprint

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Klebsiella pneumoniaeis a gram-negative, encapsulated, non-motile bacterium that can cause damage to human lungs. Antibiotic resistance of this strain requires constant monitoring and for this purpose, Oxford nanopore mediated whole genome sequencing was done for a strain acquired from the pleural fluid of a diabetic patient suffering from chronic kidney disease. A genome of 5.98 MB was obtained, with 8,869 CDSs and 110 RNAs. Around 96 proteins were seen as involved in virulence, disease or defense, while 25 antibiotic resistance genes were identified. Pan-genome was inferred as open, with 12,857 and 1,303 CDSs forming respective accessory and core genome of antibiotic resistant Pakistani strains (n=168) of this species. Apart from notable antimicrobial resistance genes like beta-lactamases, a gene conferring resistance to colistin was also mined. To the best of our knowledge, this is first report of nanopore mediated long read sequencing of a hypermucoviscous virulentK. pneumoniaefrom Pakistan.

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A sophisticated virulence repertoire and colistin resistance of Citrobacter freundii ST150 from a patient with sepsis admitted to ICU in a tertiary care hospital in Uganda, East Africa: Insight from genomic and molecular docking analyses

Maghembe,

Magulye,

Eilu

et al. 2024

Infection, Genetics and Evolution

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Elucidation of molecular mechanism for colistin resistance among Gram-negative isolates from tertiary care hospitals

Cited by 5 publications

References 33 publications

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings

Nanopore sequencing of antibiotic-resistantKlebsiella pneumoniaeJRCGR1 isolate from Pakistan and country scale pan-genomics

A sophisticated virulence repertoire and colistin resistance of Citrobacter freundii ST150 from a patient with sepsis admitted to ICU in a tertiary care hospital in Uganda, East Africa: Insight from genomic and molecular docking analyses

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