Journal Article
- Detection of colistin-resistant populations prior to antibiotic exposure in KPC-2-producing Klebsiella pneumoniae clinical isolates
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Jungyu Seo , Yu Mi Wi , Jong Min Kim , Yae-Jean Kim , Kwan Soo Ko
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J. Microbiol. 2021;59(6):590-597. Published online March 29, 2021
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DOI: https://doi.org/10.1007/s12275-021-0610-1
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Abstract
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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.
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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.2024;[Epub] 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'ts
- Trichoderma reesei Sch9 and Yak1 regulate vegetative growth, conidiation, and stress response and induced cellulase production
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Xinxing Lv† , Weixin Zhang† , Guanjun Chen , Weifeng Liu
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J. Microbiol. 2015;53(4):236-242. Published online January 31, 2015
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DOI: https://doi.org/10.1007/s12275-015-4639-x
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50
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Abstract
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Protein kinases are key players in controlling many basic
cellular processes in almost all the organisms via mediating
signal transduction processes. In the present study, we characterized
the cellulolytic Trichoderma reesei orthologs of
Saccharomyces cerevisiae Sch9 and Yak1 by sequence alignment
and functional analysis. The T. reesei Trsch9Δ and
Tryak1Δ mutant strains displayed a decreased growth rate
on different carbon sources and produced less conidia. The
absence of these two kinases also resulted in different but
abnormal polarized apical growth as well as sensitivity to
various stresses. In addition, disruption of the genes Trsch9 or
Tryak1 resulted in perturbation of cell wall integrity. Interestingly,
while the induced production of cellulases was slightly
compromised in the Trsch9Δ strain, the extracellular production
of cellulases was significantly improved in the absence
of Yak1. The results indicate that TrSch9 and TrYak1
play an important role in filamentous growth, stress response
and induced production of cellulases in T. reesei.
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Citations
Citations to this article as recorded by

- Enhancing cellulase production in Neurospora crassa through combined deletion of the phospholipase D-encoding gene pla-7 and modulation of transcription factor CLR-2 expression
Yifan Chen, Haowen Sun, Huizhen Chen, Jiaming Wu, Jianzhong Huang, Xianzhang Jiang, Lina Qin
International Journal of Biological Macromolecules.2025; 307: 141944. CrossRef - Transcriptomics and co-expression network analysis revealing candidate genes for the laccase activity of Trametes gibbosa
Jie Chen, Yi Ye, Yujie Chi, Xin Hao, Qingquan Zhao
BMC Microbiology.2023;[Epub] CrossRef - Kinase POGSK-3β modulates fungal plant polysaccharide-degrading enzyme production and development
Ting Zhang, Han-Zhi Li, Wen-Tong Li, Di Tian, Yuan-Ni Ning, Xue Liang, Jing Tan, Yan-Hao Zhao, Xue-Mei Luo, Jia-Xun Feng, Shuai Zhao
Applied Microbiology and Biotechnology.2023; 107(11): 3605. CrossRef - Assessing the intracellular primary metabolic profile of Trichoderma reesei and Aspergillus niger grown on different carbon sources
Gustavo Pagotto Borin, Juliana Velasco de Castro Oliveira
Frontiers in Fungal Biology.2022;[Epub] CrossRef - AGC/AKT Protein Kinase SCH9 Is Critical to Pathogenic Development and Overwintering Survival in Magnaporthe oryzae
Wajjiha Batool, Chang Liu, Xiaoning Fan, Penghui Zhang, Yan Hu, Yi Wei, Shi-Hong Zhang
Journal of Fungi.2022; 8(8): 810. CrossRef - High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12
Ai-Ping Pang, Haiyan Wang, Funing Zhang, Xin Hu, Fu-Gen Wu, Zhihua Zhou, Wei Wang, Zuhong Lu, Fengming Lin
Biotechnology for Biofuels.2021;[Epub] CrossRef - Candida glabrata Yap6 Recruits Med2 To Alter Glycerophospholipid Composition and Develop Acid pH Stress Resistance
Pei Zhou, Xiaoke Yuan, Hui Liu, Yanli Qi, Xiulai Chen, Liming Liu, Isaac Cann
Applied and Environmental Microbiology.2020;[Epub] CrossRef - Biocontrol potential of Trichoderma asperellum mutants T39 and T45 and their growth promotion of poplar seedlings
Ruiting Guo, Zhiying Wang, Chang Zhou, Ying Huang, Haijuan Fan, Yucheng Wang, Zhihua Liu
Journal of Forestry Research.2020; 31(3): 1035. CrossRef - Broad Substrate-Specific Phosphorylation Events Are Associated With the Initial Stage of Plant Cell Wall Recognition in Neurospora crassa
Maria Augusta C. Horta, Nils Thieme, Yuqian Gao, Kristin E. Burnum-Johnson, Carrie D. Nicora, Marina A. Gritsenko, Mary S. Lipton, Karthikeyan Mohanraj, Leandro José de Assis, Liangcai Lin, Chaoguang Tian, Gerhard H. Braus, Katherine A. Borkovich, Monika
Frontiers in Microbiology.2019;[Epub] CrossRef - The influence of feedstock characteristics on enzyme production in Trichoderma reesei: a review on productivity, gene regulation and secretion profiles
Vera Novy, Fredrik Nielsen, Bernhard Seiboth, Bernd Nidetzky
Biotechnology for Biofuels.2019;[Epub] CrossRef - STK-12 acts as a transcriptional brake to control the expression of cellulase-encoding genes in Neurospora crassa
Liangcai Lin, Shanshan Wang, Xiaolin Li, Qun He, J. Philipp Benz, Chaoguang Tian, Katherine A. Borkovich
PLOS Genetics.2019; 15(11): e1008510. CrossRef - Involvement of BcYak1 in the Regulation of Vegetative Differentiation and Adaptation to Oxidative Stress of Botrytis cinerea
Qianqian Yang, Jianan Zhang, Jicheng Hu, Xue Wang, Binna Lv, Wenxing Liang
Frontiers in Microbiology.2018;[Epub] CrossRef - Role of Trichoderma reesei mitogen-activated protein kinases (MAPKs) in cellulase formation
Mingyu Wang, Meiling Zhang, Ling Li, Yanmei Dong, Yi Jiang, Kuimei Liu, Ruiqin Zhang, Baojie Jiang, Kangle Niu, Xu Fang
Biotechnology for Biofuels.2017;[Epub] CrossRef - A copper-responsive promoter replacement system to investigate gene functions in Trichoderma reesei: a case study in characterizing SAGA genes
Fanglin Zheng, Yanli Cao, Xinxing Lv, Lei Wang, Chunyan Li, Weixin Zhang, Guanjun Chen, Weifeng Liu
Applied Microbiology and Biotechnology.2017; 101(5): 2067. CrossRef - The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence
Patrícia Alves de Castro, Thaila Fernanda dos Reis, Stephen K. Dolan, Adriana Oliveira Manfiolli, Neil Andrew Brown, Gary W. Jones, Sean Doyle, Diego M. Riaño‐Pachón, Fábio Márcio Squina, Camila Caldana, Ashutosh Singh, Maurizio Del Poeta, Daisuke Hagiwar
Molecular Microbiology.2016; 102(4): 642. CrossRef
- Effects of Exopolysaccharide Production on Liquid Vegetative Growth, Stress Survival, and Stationary Phase Recovery in Myxococcus xanthus
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Wei Hu , Jing Wang , Ian McHardy , Renate Lux , Zhe Yang , Yuezhong Li , Wenyuan Shi
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J. Microbiol. 2012;50(2):241-248. Published online April 27, 2012
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DOI: https://doi.org/10.1007/s12275-012-1349-5
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Abstract
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Exopolysaccharide (EPS) of Myxococcus xanthus is a wellregulated
cell surface component. In addition to its known
functions for social motility and fruiting body formation
on solid surfaces, EPS has also been proposed to play a role
in multi-cellular clumping in liquid medium, though this
phenomenon has not been well studied. In this report, we
confirmed that M. xanthus clumps formed in liquid were
correlated with EPS levels and demonstrated that the EPS
encased cell clumps exhibited biofilm-like structures. The
clumps protected the cells at physiologically relevant EPS
concentrations, while cells lacking EPS exhibited significant
reduction in long-term viability and resistance to stressful
conditions. However, excess EPS production was counterproductive
to vegetative growth and viable cell recovery declined
in extended late stationary phase as cells became
trapped in the matrix of clumps. Therefore, optimal EPS
production by M. xanthus is important for normal physiological
functions in liquid.