Article
Immunology
Miaomiao Xie, Kaichao Chen, Ning Dong, Qi Xu, Edward Wai-Chi Chan, Rong Zhang, Sheng Chen
Summary: Study findings showed that colistin-resistant K. pneumoniae strains had increased fitness and biofilm formation potential in vitro, as well as higher survival rates in the presence of normal human serum. Interestingly, these strains exhibited reduced virulence in a mouse infection model but enhanced virulence in a Galleria mellonella infection model. Infection with colistin-resistant strains also resulted in lower expression levels of inflammatory cytokines and significantly decreased bacterial loads.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Xuemei Yang, Qiaoling Sun, Jiaping Li, Yu Jiang, Yi Li, Jianping Lin, Kaichao Chen, Edward Wai-Chi Chan, Rong Zhang, Sheng Chen
Summary: The epidemiological features and potential threat to human health of the newly emerged carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) are currently unknown. This study analyzed 784 CRKP strains collected from three hospitals in China and found that the proportion of CRKP strains among clinical K. pneumoniae strains increased sharply. A significant number of these CRKP strains carried a virulence-encoding plasmid, but only a small percentage exhibited a hypervirulent phenotype. Genetic markers were not strongly correlated with hypervirulent phenotypes, indicating that additional factors may contribute to the hypervirulence of CRKP. The transmission of these CRKP strains in China likely involved multiple clones of ST11 and the major mechanism of carbapenem resistance was the carriage of IncFII pSWU01-like, bla (KPC-2)-bearing plasmids. These findings highlight the rapid increase in prevalence of CRKP strains carrying virulence plasmids in China and the need for better definition and screening of truly hypervirulent CR-HvKP strains in clinical settings.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Infectious Diseases
Xiaoxue Liang, Ping Chen, Baoguo Deng, Feng-Hui Sun, Yongqiang Yang, Yanxian Yang, Ruowen He, Mingyang Qin, Yiping Wu, Fan Yang, Guo-Bao Tian, Min Dai
Summary: This study compared the antimicrobial resistance, virulence, clinical characteristics, and risk factors between carbapenem-resistant K. pneumoniae (CRKP) and carbapenem-susceptible K. pneumoniae (CSKP) isolates from patients with bloodstream infections (BSIs) in China. The results demonstrated that CRKP isolates were more drug-resistant, more virulent, and associated with poorer outcomes compared to CSKP isolates.
INFECTION AND DRUG RESISTANCE
(2022)
Article
Infectious Diseases
Mykhailo Savin, Gabriele Bierbaum, Nico T. Mutters, Ricarda Maria Schmithausen, Judith Kreyenschmidt, Isidro Garcia-Menino, Silvia Schmoger, Annemarie Kaesbohrer, Jens Andre Hammerl
Summary: This study characterizes carbapenem-resistant Klebsiella spp. in wastewater and surface water in Germany. The isolates showed resistance to multiple antibiotics and a high diversity of antibiotic-resistance genes. Virulence factors were also present in most isolates. The findings suggest the possible dissemination of resistant bacteria in the environment and the risk of colonization and infection in humans, livestock, and wildlife.
Article
Pharmacology & Pharmacy
Ying Zhou, Chunyang Wu, Bingjie Wang, YanLei Xu, Huilin Zhao, Yinjuan Guo, Xiaocui Wu, Jingyi Yu, Lulin Rao, Xinyi Wang, Fangyou Yu
Summary: This study found that high-virulence K. pneumoniae strains (KL1/KL2) have lower resistance to antibiotics compared to carbapenem-resistant K. pneumoniae strains (CRKP). It also discovered that the pLVPK-like virulence plasmid and IncF blaKPC-2 plasmid are crucial for the formation of hypervirulent and carbapenem-resistant K. pneumoniae.
DRUG RESISTANCE UPDATES
(2023)
Article
Immunology
Katariina Koskinen, Reetta Penttinen, Anni-Maria Ormala-Odegrip, Christian G. Giske, Tarmo Ketola, Matti Jalasvuori
Summary: The extensively drug resistant Klebsiella pneumoniae poses a significant burden to healthcare systems worldwide, with certain sequence types being more prevalent in hospital settings. There are clear differences between isolates, and drought tolerance was found to notably associate with non-epidemic strains of K. pneumoniae.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Dakang Hu, Wenjie Chen, Qi Zhang, Meng Li, Zehua Yang, Yong Wang, Yunkun Huang, Gang Li, Dongxing Tian, Pan Fu, Weiwen Wang, Ping Ren, Qing Mu, Lianhua Yu, Xiaofei Jiang
Summary: This study investigated the epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) and hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) in mainland China. Molecular determination of CR-HvKP and Hv-CRKP showed biases compared to mouse lethality test, with the exact prevalence of CR-HvKP being less than 1.0% and that of Hv-CRKP even lower.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Infectious Diseases
Theodoros Karampatakis, Katerina Tsergouli, Payam Behzadi
Summary: Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for various infections. Carbapenem-resistant K. pneumoniae (CRKP) pose a major threat to public health, with high mortality rates in immunocompromised and critically ill patients. Understanding the virulence factors, molecular epidemiology, and treatment options for CRKP is crucial.
Review
Pharmacology & Pharmacy
Xinqian Ma, Wen Xi, Deqing Yang, Lili Zhao, Wenyi Yu, Yukun He, Wentao Ni, Zhancheng Gao
Summary: Bacteria can develop increased sensitivity to certain antibiotics after acquiring resistance to another antibiotic, known as collateral sensitivity. Exploiting collateral sensitivity in treatment design could effectively suppress or reverse resistance evolution.
DRUG RESISTANCE UPDATES
(2023)
Review
Microbiology
Yu-Ling Han, Xu-Hui Wen, Wen Zhao, Xi-Shan Cao, Jian-Xun Wen, Jun-Rui Wang, Zhi-De Hu, Wen-Qi Zheng
Summary: CR-hvKP, a type of Klebsiella pneumoniae, exhibits both hypervirulence and carbapenem resistance phenotypes, causing severe infections and posing significant challenges to global public health. The evolutionary mechanisms include horizontal transfer of plasmids carrying resistance and virulence genes.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Infectious Diseases
Fanbo Lu, Luwen Zhang, Juanjuan Ji, Yuanhong Xu, Bo Wang, Jinxing Xia
Summary: This study aimed to investigate the epidemiological and antimicrobial resistant patterns, clinical characteristics and risk factors of critically ill patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) from intensive care units (ICUs). The study found that CRKP strains exhibited significantly strong resistance against major antimicrobial agents, and the risk of CRKP infection was associated with recent exposure to certain antibiotics and prior treatment with invasive interventions.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Biotechnology & Applied Microbiology
Zhengjiang Jin, Zhenhui Wang, Lin Gong, Lu Yi, Nian Liu, Lan Luo, Wenting Gong
Summary: In this study, whole-genome sequencing was conducted on 34 carbapenem-resistant Klebsiella pneumoniae strains. It was found that these strains carried multiple antibiotic resistance genes and virulence genes, and demonstrated resistance to various disinfectants. Variations were observed in the virulence, drug resistance, and disinfectant tolerance among different strains.
Article
Immunology
Courtney L. Luterbach, Liang Chen, Lauren Komarow, Belinda Ostrowsky, Keith S. Kaye, Blake Hanson, Cesar A. Arias, Samit Desai, Jason C. Gallagher, Elizabeth Novick, Stephen Pagkalinawan, Ebbing Lautenbach, Glenn Wortmann, Robert C. Kalayjian, Brandon Eilertson, John J. Farrell, Todd McCarty, Carol Hill, Vance G. Fowler, Barry N. Kreiswirth, Robert A. Bonomo, David van Duin
Summary: This study evaluated the clustering of carbapenem-resistant Klebsiella pneumoniae (CRKp) among patients in US hospitals and identified widespread intrasystem and intersystem transmission. Different methods for assessing genetic similarity resulted in only minor differences in interpretation.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Pharmacology & Pharmacy
Jintao He, Qiucheng Shi, Zhifu Chen, Wang Zhang, Peng Lan, Qingye Xu, Huangdu Hu, Qiong Chen, Jianzhong Fan, Yan Jiang, Belinda Loh, Sebastian Leptihn, Quanming Zou, Jinyong Zhang, Yunsong Yu, Xiaoting Hua
Summary: The aim of this study was to investigate the in vivo evolution of the mucoid phenotype of ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) and gain insights into the diverse evolution and biology of these strains. Whole genome sequencing and bioinformatic analysis were used to determine the mutations involved in the mucoid phenotype. Gene knockout, bacterial morphology, and CPS extraction were used to verify the roles of wzc and wcaJ in the mucoid phenotypes. Antimicrobial susceptibility, growth assay, biofilm formation, host cell adhesion, and virulence assay were used to investigate the pleiotropic role of CPS changes in the CRKP strains.
DRUG RESISTANCE UPDATES
(2023)
Article
Infectious Diseases
Jingxuan Zhu, Ye Chen, Xuejing Yang
Summary: This study investigated the antibiotic resistance and molecular characteristics of CRKP strains isolated in Zhejiang Province, China, revealing that CRKP isolates in ICU showed significantly higher resistance rates than those in general ward patients, 50 strains carried the blaKPC gene, and pulmonary disease may affect the prognosis of CRKP infection.
INFECTION AND DRUG RESISTANCE
(2022)
Article
Multidisciplinary Sciences
Gustavo C. Cerqueira, Ashlee M. Earl, Christoph M. Ernst, Yonatan H. Grad, John P. Dekker, Michael Feldgarden, Sinead B. Chapman, Joao L. Reis-Cunha, Terrance P. Shea, Sarah Young, Qiandong Zeng, Mary L. Delaney, Diane Kim, Ellena M. Peterson, Thomas F. O'Brien, Mary Jane Ferraro, David C. Hooper, Susan S. Huang, James E. Kirby, Andrew B. Onderdonk, Bruce W. Birren, Deborah T. Hung, Lisa A. Cosimi, Jennifer R. Wortman, Cheryl I. Murphy, William P. Hanage
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Immunology
Sergio I. Valdes-Ferrer, Jose C. Crispin, Pablo F. Belaunzaran-Zamudio, Carlos A. Rodriguez-Osorio, Bernardo Cacho-Diaz, Jorge Alcocer-Varela, Carlos Cantu-Brito, Juan Sierra-Madero
FRONTIERS IN IMMUNOLOGY
(2017)
Article
Genetics & Heredity
Leah C. Kottyan, Avery Maddox, Julian R. Braxton, Emily M. Stucke, Vince Mukkada, Philip E. Putnam, J. Pablo Abonia, Mirna Chehade, Robert A. Wood, Robbie D. Pesek, Brian P. Vickery, Glenn T. Furuta, Peter Dawson, Hugh A. Sampson, Lisa J. Martin, Jennifer A. Kelly, Robert P. Kimberly, Kathy Sivils, Patrick M. Gaffney, Kenneth Kaufman, John B. Harley, Marc E. Rothenberg
GENES AND IMMUNITY
(2019)
Article
Microbiology
Peijun Ma, Hannah H. Laibinis, Christoph M. Ernst, Deborah T. Hung
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2018)
Article
Cell Biology
Margarita Parada-Kusz, Cristina Penaranda, Elliott J. Hagedorn, Anne Clatworthy, Anil V. Nair, Jonathan E. Henninger, Christoph Ernst, Brian Li, Raquel Riquelme, Humberto Jijon, Eduardo J. Villablanca, Leonard I. Zon, Deborah Hung, Miguel L. Allende
DISEASE MODELS & MECHANISMS
(2018)
Article
Infectious Diseases
Carlos A. Rodriguez-Osorio, Cesar O. Sanchez-Martinez, Javier Araujo-Melendez, Elia Criollo, Alejandro E. Macias-Hernandez, Alfredo Ponce-de-Leon, Sergio Ponce-de-Leon, Jose Sifuentes-Osornio
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2015)
Article
Microbiology
Christoph M. Ernst, Christoph J. Slavetinsky, Sebastian Kuhn, Janna N. Hauser, Mulugeta Nega, Nagendra N. Mishra, Cordula Gekeler, Arnold S. Bayer, Andreas Peschel
Correction
Biochemistry & Molecular Biology
Christoph M. Ernst, Julian R. Braxton, Carlos A. Rodriguez-Osorio, Anna P. Zagieboylo, Li Li, Alejandro Pironti, Abigail L. Manson, Anil V. Nair, Maura Benson, Kaelyn Cummins, Anne E. Clatworthy, Ashlee M. Earl, Lisa A. Cosimi, Deborah T. Hung
Article
Biology
Peijun Ma, Lorrie L. He, Alejandro Pironti, Hannah H. Laibinis, Christoph M. Ernst, Abigail L. Manson, Roby P. Bhattacharyya, Ashlee M. Earl, Jonathan Livny, Deborah T. Hung
Summary: Genetic factors such as high-level transposon insertional mutagenesis and a broader spectrum of resistance-conferring mutations have been identified as facilitators for the evolution of carbapenem resistance in Klebsiella pneumoniae. Loss of systems that restrict horizontal resistance gene uptake, such as the CRISPR-Cas system, also play a role in resistance evolution. Consideration of both current and future efficacy of antibiotics, as well as the genetic background and antibiotic identity of clinical isolates, are important determinants of the propensity for resistance development.
Article
Biology
Christoph J. Slavetinsky, Janna N. Hauser, Cordula Gekeler, Jessica Slavetinsky, Andre Geyer, Alexandra Kraus, Doris Heilingbrunner, Samuel Wagner, Michael Tesar, Bernhard Krismer, Sebastian Kuhn, Christoph M. Ernst, Andreas Peschel
Summary: The pandemic of antibiotic resistance is a major threat to human health, and new antimicrobial strategies are needed. Multiple peptide resistance factor (MprF) is a key factor that increases the resistance of methicillin-resistant Staphylococcus aureus (MRSA) and other pathogens to host defense peptides and antibiotics. In this study, monoclonal antibodies targeting MprF were developed, and an antibody called M-C7.1 was found to sensitize MRSA to antimicrobial peptides and antibiotics, as well as impair its survival in human phagocytes. These findings suggest that MprF inhibitors could be used as a new antivirulence approach against MRSA and other bacterial pathogens.
Review
Biochemistry & Molecular Biology
Julian R. Braxton, Daniel R. Southworth
Summary: p97/valosin-containing protein is a significant therapeutic target due to its essential functions and association with neurodegenerative disease and cancer. Adapter partner proteins play a crucial role in coordinating p97 activity and enabling its diverse functions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Julian R. Braxton, Chad R. Altobelli, Maxwell R. Tucker, Eric Tse, Aye C. Thwin, Michelle R. Arkin, Daniel R. Southworth
Summary: This study reports the structures of p97 protein bound to the UBXD1 adaptor and identifies UBXD1 as a potent ATPase inhibitor of p97. The structures, mutagenesis, and comparisons with other adaptors reveal how UBXD1 regulates the ATPase activity and structure of p97.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)