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Detection of colistin-resistant populations prior to antibiotic exposure in KPC-2-producing Klebsiella pneumoniae clinical isolates
Jungyu Seo , Yu Mi Wi , Jong Min Kim , Yae-Jean Kim , Kwan Soo Ko
J. Microbiol. 2021;59(6):590-597.   Published online March 29, 2021
DOI: https://doi.org/10.1007/s12275-021-0610-1
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  • 11 Web of Science
  • 9 Crossref
AbstractAbstract PDF
Although colistin is frequently regarded as the antibiotic of last resort in treating carbapenem-resistant Klebsiella pneumoniae, colistin heteroresistance may in part be associated with antibiotic treatment failure. However, we do not know how widespread the colistin heteroresistance is in carbapenem- resistant K. pneumoniae isolates. In this study, we performed colistin disc diffusion assays, E-tests, and population analysis profiling for KPC-2-producing K. pneumoniae isolates to identify colistin heteroresistance. Although no colistin- resistant colonies were detected by the disc diffusion test and E-test, a colistin-resistant subpopulation was identified in population analysis profiling in all colistin-susceptible, KPC-2-producing K. pneumoniae isolates. Colistin-resistant subpopulations were also identified even when isolates had no colistin exposure. The ratio of colistin-resistant subpopulations to the total population increased as the exposure concentration of colistin increased. In in vitro time-kill assays, regrowth was observed in all isolates after 2 h upon exposure to colistin. We identified common amino acid alterations in PhoQ, PhoP, and PmrB in colistin-resistant subpopulations from some isolates, but no substitutions were found in most resistant subpopulations from other isolates. In all colistin-resistant subpopulations, overexpression of PhoQ and PbgP was observed. In this study, we demonstrated that colistin heteroresistance may be common in KPC-2-producing K. pneumoniae isolates, which could not be detected in the disc diffusion method and E-test. Colistin heteroresistance may cause colistin treatment failure in part and may evolve into resistance. Thus, development of more reliable diagnostic methods is required to detect colistin heteroresistance.

Citations

Citations to this article as recorded by  
  • High prevalence of polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae and its within-host evolution to resistance among critically ill scenarios
    Xiaoli Wang, Tianjiao Meng, Yunqi Dai, Hong-Yu Ou, Meng Wang, Bin Tang, Jingyong Sun, Decui Cheng, Tingting Pan, Ruoming Tan, Hongping Qu
    Infection.2025; 53(1): 271.     CrossRef
  • Development of colistin resistance via heteroresistance modeling in Klebsiella pneumoniae: A diagnostic study
    Jungyu Seo, Kwan Soo Ko
    Precision and Future Medicine.2024; 8(1): 10.     CrossRef
  • Conversion to colistin susceptibility by tigecycline exposure in colistin-resistant Klebsiella pneumoniae and its implications to combination therapy
    Suyeon Park, Jihyun Choi, Dongwoo Shin, Ki Tae Kwon, Si-Ho Kim, Yu Mi Wi, Kwan Soo Ko
    International Journal of Antimicrobial Agents.2024; 63(1): 107017.     CrossRef
  • Insight into Antibiotic Synergy Combinations for Eliminating Colistin Heteroresistant Klebsiella pneumoniae
    Sahaya Glingston Rajakani, Basil Britto Xavier, Adwoa Sey, El Bounja Mariem, Christine Lammens, Herman Goossens, Youri Glupczynski, Surbhi Malhotra-Kumar
    Genes.2023; 14(7): 1426.     CrossRef
  • Mechanisms and Clinical Relevance ofPseudomonas aeruginosaHeteroresistance
    Zhao Chen
    Surgical Infections.2023; 24(1): 27.     CrossRef
  • Heteroresistance Is Associated With in vitro Regrowth During Colistin Treatment in Carbapenem-Resistant Klebsiella pneumoniae
    Yifan Wang, Xinqian Ma, Lili Zhao, Yukun He, Wenyi Yu, Shining Fu, Wentao Ni, Zhancheng Gao
    Frontiers in Microbiology.2022;[Epub]     CrossRef
  • Prevalence of Mutated Colistin-Resistant Klebsiella pneumoniae: A Systematic Review and Meta-Analysis
    Nik Yusnoraini Yusof, Nur Iffah Izzati Norazzman, Siti Nur’ain Warddah Ab Hakim, Mawaddah Mohd Azlan, Amy Amilda Anthony, Fatin Hamimi Mustafa, Naveed Ahmed, Ali A. Rabaan, Souad A. Almuthree, Abdulsalam Alawfi, Amer Alshengeti, Sara Alwarthan, Mohammed G
    Tropical Medicine and Infectious Disease.2022; 7(12): 414.     CrossRef
  • Antibiotic Heteroresistance in Klebsiella pneumoniae
    Karolina Stojowska-Swędrzyńska, Adrianna Łupkowska, Dorota Kuczyńska-Wiśnik, Ewa Laskowska
    International Journal of Molecular Sciences.2021; 23(1): 449.     CrossRef
  • Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions
    Kathleen Tompkins, David van Duin
    European Journal of Clinical Microbiology & Infectious Diseases.2021; 40(10): 2053.     CrossRef
Research Support, Non-U.S. Gov't
The Use of Pseudomonas fluorescens P13 to Control Sclerotinia Stem Rot (Sclerotinia sclerotiorum) of Oilseed Rape
Hui Li , Huaibo Li , Yan Bai , Jing Wang , Ming Nie , Bo Li , Ming Xiao
J. Microbiol. 2011;49(6):884-889.   Published online December 28, 2011
DOI: https://doi.org/10.1007/s12275-011-1261-4
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  • 28 Scopus
AbstractAbstract PDF
Sclerotinia stem rot (SSR) caused by the fungus Sclerotinia sclerotiorum has been an increasing threat to oilseed rape (Brassica napus L.) cultivation. Efficient and environment‐friendly treatments are much needed. Here we focus on microbial control. The Pseudomonas fluorescens P13 that was isolated from oilseed rape cultivation soil, proved to be a useful biocontrol strain for application. Morphology, physiological and biochemical tests and 16S rDNA analysis demonstrated that it was P. fluorescens P13 and that it had a broad antagonistic spectrum, significantly lessening the mycelial growth of S. sclerotiorum by 84.4% and suppressing sclerotial formation by 95‐100%. Scanning electron microscopy studies attested that P13 deformed S. sclerotiorum mycelia when they were cultured together. P13 did not produce chitinase but did produce hydrogen cyanide (HCN) which was likely one of the antagonistic mechanisms. The density of P13 remained at a high level (≥106 CFU/ml) during 5 weeks in the rhizosphere soil and roots. P13 reduced SSR severity at least by 59% in field studies and also promoted seedling growth (p<0.05) at the seedling stage. From these data, our work provided evidence that P13 could be a good alternative biological resource for biocontrol of S. sclerotiorum.

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