Functional Genome Screening to Elucidate the Colistin Resistance Mechanism

  title={Functional Genome Screening to Elucidate the Colistin Resistance Mechanism},
  author={Mohit Kumar and Ashutosh Gupta and Rajesh Kumar Sahoo and Jayanti Jena and Nagen Kumar Debata and Enketeswara Subudhi},
  journal={Scientific Reports},
Antibiogram profile of 1590 clinical bacterial isolates based on thirteen different antimicrobial compounds showed that 1.6% of the bacterial isolates are multidrug resistant. Distribution pattern based on 16S rRNA sequence analysis showed that Pseudomonas aeruginosa constituted the largest group (83.6%) followed by Burkholderia pseudomallei sp. A191 (5.17%), Staphylococcus sp. A261 (3.45%). Among the various antibiotics used, colistin appeared to be the most effective against the Gram negative… 
Colistin resistance in Gram-negative bacteria analysed by five phenotypic assays and inference of the underlying genomic mechanisms
Colistin resistance in diverse species occurred predominantly through spontaneous chromosomal mutation rather than plasmid-mediated resistance, and the Rapid Polymyxin™ NP test showed highest categorical concords and the UMIC test provided MIC values with high concordance to BMD.
Molecular prevalence of resistance determinants, virulence factors and capsular serotypes among colistin resistance carbapenemase producing Klebsiella pneumoniae: a multi-centric retrospective study
Similar virulence and resistance typing among the isolates suggest hospital-acquired infection in a health care setup, and a strong correlation between ERIC and (GTG)5 genotyping method was established with antimicrobial resistance patterns and virulence determinants at P < 0.05, while no correlation was found with capsular serotypes.
Genotypic validation of extended-spectrum β-lactamase and virulence factors in multidrug resistance Klebsiella pneumoniae in an Indian hospital
The resistance profile data obtained from the present study can serve as the information base to understand the infection pattern prevailing in the hospital and for physicians to recommend suitable antibiotics for the patients.
Molecular mechanisms of polymyxin resistance: knowns and unknowns.
How to discover new antibiotic resistance genes?
This review describes the different methods that could be used to characterize new ARGs using classic or innovative methods, and focuses on biochemical methods, molecular methods, next-generation sequencing and bioinformatics approaches.
Regulation of Virulence by Two-Component Systems in Pathogenic Burkholderia
This review will highlight TCS that have been described to play a role in virulence in either the BCC or B. pseudomallei, which is the causative agent of melioidosis, a serious disease that occurs in the tropics, and a potential bioterrorism weapon.
A severe leakage of intermediates to shunt products in acarbose biosynthesis
It is shown that shunt pathways and inefficient amino-deoxyhexose biosynthesis lead to 1- epi -valienol and valienol accumulation, and minimizing the flux to these shunt products can increase acarbose titer in Actinoplanes  species.


Colistin Resistance in Acinetobacter baumannii Is Mediated by Complete Loss of Lipopolysaccharide Production
It is shown that A. baumannii can rapidly develop resistance to polymyxin antibiotics by complete loss of the initial binding target, the lipid A component of lipopolysaccharide (LPS), which has long been considered to be essential for the viability of Gram-negative bacteria.
Genomic and Transcriptomic Analyses of Colistin-Resistant Clinical Isolates of Klebsiella pneumoniae Reveal Multiple Pathways of Resistance
Genetic mechanisms that lead to resistance to colistin (Colr) in K. pneumoniae are not fully characterized, but separate mutations were found in a previously uncharacterized histidine kinase gene that is part of a two-component regulatory system (TCRS) now designated crrAB.
A single amino acid substitution in PmrB is associated with polymyxin B resistance in clinical isolate of Pseudomonas aeruginosa.
Results suggest that amino acid substitution in PmrB is one mechanism of polymyxin B resistance in clinical isolates of P. aeruginosa.
Mutations and expression of PmrAB and PhoPQ related with colistin resistance in Pseudomonas aeruginosa clinical isolates.
  • Ji-Young Lee, K. Ko
  • Biology, Medicine
    Diagnostic microbiology and infectious disease
  • 2014
Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in Klebsiella pneumoniae CG43
A role of the capsular polysaccharide level and the pmr genes for K. pneumoniae resistance to polymyxin B is reported and the PmrD connector-mediated pathway in governing the regulation of pmr expression was demonstrated.
In Vivo Emergence of Colistin Resistance in Klebsiella pneumoniae Producing KPC-Type Carbapenemases Mediated by Insertional Inactivation of the PhoQ/PhoP mgrB Regulator
Findings confirmed the MgrB regulatory role in K. pneumoniae and were in agreement with the known association between upregulation of the PhoQ/PhoP system and activation of the pmrHFIJKLM operon, which eventually leads to resistance to polymyxins by modification of the lipopolysaccharide target.
PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients
Results indicate that phoQ loss-of-function mutations can contribute to high-level polymyxin resistance in clinical strains of P. aeruginosa.
Colistin Resistance Mechanisms in Klebsiella pneumoniae Strains from Taiwan
This study showed that capsular type K64 and ST11 are the prevalent capsular and sequence types in the colistin-resistant strains in Taiwan and novel single amino acid changes in MgrB and PhoQ were observed to contribute tocolistin resistance.
Emergence of tigecycline & colistin resistant Acinetobacter baumanii in patients with complicated urinary tract infections in north India
A prospective study was conducted to report emergence of PDR Acb complex which were also resistant to tigecycline and colistin, and the isolates were labelled as susceptible, intermediate sensitive and resistant based on inhibition zones as per standard guidelines.
Colistin resistance in Klebsiella pneumoniae.