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Published on: October 31, 2014
PmrAB and PhoPQ Variants in Colistin-Resistant Enterobacter spp. Isolates in Korea
Yoon-Kyoung Hong1, Kwan Soo Ko2
1Department of Molecular Cell Biology and Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.
Abstract:
In this study, we investigated the amino acid variations and mRNA expression of PhoPQ and PmrAB two-component regulatory systems in colistin-resistant Enterobacter cloacae isolates from Korea. We determined the nucleotide sequences of phoP, phoQ, pmrA, and pmrB in 51 colistin-resistant, 5 colistin-susceptible, and 8 skip-well isolates and consequently, the corresponding amino acid sequences as well. PhoPQ and PmrAB sequences showed large variations among the isolates (14, 67, 20, and 68 sites, respectively). Although there was some discrepancy between the genes, the colistin-resistant E. cloacae isolates were grouped into four clades and the susceptible isolates were grouped into two clades. We did not find any distinct amino acid substitutions associated with colistin resistance. Furthermore, mRNA expression of phoQ and pmrB was not significantly higher in the colistin-resistant isolates. Our data suggests that the colistin resistance mechanisms might be different in E. cloacae when compared to other gram-negative bacteria.
Insights
Colistin resistance in Enterobacter cloacae may not involve common PhoPQ and PmrAB gene variations. Further research is needed to understand resistance mechanisms in this bacterium.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- Colistin is a critical antibiotic for treating multidrug-resistant Gram-negative infections.
- Enterobacter cloacae is an opportunistic pathogen frequently associated with healthcare-associated infections.
- Mechanisms of colistin resistance in Enterobacter cloacae are not fully elucidated.
Purpose of the Study:
- To investigate amino acid variations in PhoPQ and PmrAB two-component regulatory systems.
- To analyze mRNA expression of PhoPQ and PmrAB systems in colistin-resistant Enterobacter cloacae.
- To compare genetic profiles of colistin-resistant, susceptible, and skip-well Enterobacter cloacae isolates.
Main Methods:
- Sequencing of phoP, phoQ, pmrA, and pmrB genes in 51 colistin-resistant, 5 colistin-susceptible, and 8 skip-well isolates.
- Analysis of corresponding amino acid sequences.
- Assessment of mRNA expression levels for phoQ and pmrB.
Main Results:
- Significant amino acid variations were observed in PhoPQ and PmrAB systems across isolates.
- No distinct amino acid substitutions were uniquely associated with colistin resistance.
- mRNA expression of phoQ and pmrB was not significantly elevated in colistin-resistant isolates.
- Phylogenetic analysis revealed distinct clades for resistant and susceptible isolates.
Conclusions:
- The study suggests that common mutations in PhoPQ and PmrAB systems may not be the primary drivers of colistin resistance in Enterobacter cloacae.
- Colistin resistance mechanisms in Enterobacter cloacae might differ from those observed in other Gram-negative bacteria.
- Further investigation into alternative resistance pathways is warranted.
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