Article
Infectious Diseases
A. M. Parrott, J. Shi, J. Aaron, D. A. Green, S. Whittier, F. Wu
Summary: Multiple strains of hypervirulent Klebsiella pneumoniae (hvKp) are emerging in New York City, associated with higher mortality compared to multidrug-resistant and classical Klebsiella infections. Co-existing hepatobiliary disease appears to be a potential risk factor for these infections.
CLINICAL MICROBIOLOGY AND INFECTION
(2021)
Review
Infectious Diseases
Junjun Chen, Huan Zhang, Xuelian Liao
Summary: Hypervirulent Klebsiella pneumoniae (hvKP), including multidrug-resistant hvKP (MDR-hvKP), is a global concern due to its ability to cause outbreaks with high pathogenicity and mortality. Key virulence agents associated with hvKP and MDR-hvKP include iron acquisition systems, increased capsule production, colibactin toxin, and hypermu-coviscosity. Recent advances have identified new hypervirulence factors and explored the evolution of MDR-hvKP. Further research is needed to identify reliable methods for detection and investigate innovative treatment targets.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Multidisciplinary Sciences
Anton Spadar, Joao Perdigao, Susana Campino, Taane G. Clark
Summary: A genome-wide association study revealed 29 potential genes associated with liver invasive and hypervirulent phenotype in Klebsiella pneumoniae. However, further large-scale studies involving more sequence types are needed to identify additional biomarkers for hypervirulence.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Chaitra Shankar, Soumya Basu, Binesh Lal, Sathiya Shanmugam, Karthick Vasudevan, Purva Mathur, Sudha Ramaiah, Anand Anbarasu, Balaji Veeraraghavan
Summary: The incidence of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hvCRKp) is increasing globally, with high-risk clones acquiring a virulence plasmid and showing phenotypic changes. Resistance to carbapenems is mainly due to OXA-232 and NDM carbapenemases. The presence of non-functional RmpA2 challenges phenotypic screening, highlighting the need for reliable markers for identifying hvCRKp.
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
Microbiology
Jie Zhu, Tao Wang, Liang Chen, Hong Du
Summary: The review summarizes the virulence factors associated with hypervirulent Klebsiella pneumoniae to understand its molecular pathogenesis and provide new strategies for improving the prevention, diagnosis, and treatment of infections caused by hvKP.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Dakang Hu, Yuming Li, Ping Ren, Dongxing Tian, Wenjie Chen, Pan Fu, Weiwen Wang, Xiaobin Li, Xiaofei Jiang
Summary: The positive rates of virulence genes in Klebsiella pneumoniae vary significantly, with iucA, p-rmpA2, and p-rmpA being the primary genes leading to Hv-bla (KPC)(+)-KP. The formation of Hv-bla (KPC)(+)-KP is mostly due to bla (KPC)(+)-KP acquiring another plasmid carrying virulence genes.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Dongjie Chen, Yingrui Zhang, Jiafang Wu, Jun Li, Han Chen, Xiaoguang Zhang, Xinlan Hu, Falin Chen, Rongguo Yu
Summary: This study evaluates the clinical and genetic virulence characteristics of critically ill patients with hypervirulent Klebsiella pneumoniae (hvKP) and classic KP (cKP) infection. It found a high rate of hvKP infection in the Chinese population, with a higher probability of septic shock in hvKP-infected patients compared to cKP-infected patients. However, survival and length of hospital stay were similar between the two groups. Risk factors for hvKP infection included hospital-acquired infection and renal insufficiency.
JOURNAL OF APPLIED MICROBIOLOGY
(2022)
Article
Microbiology
Otavio Hallal Ferreira Raro, Patrice Nordmann, Manuel Dominguez Pino, Jacqueline Findlay, Laurent Poirel
Summary: There is an increasing occurrence of multidrug-resistant (MDR) and hypervirulent (hv) Klebsiella pneumoniae (MDR-hvKp) convergent clones. These strains can cause difficult-to-treat infections and have a higher mortality rate in healthy adults. This study in Switzerland identified a rate of 9.0% K. pneumoniae with a virulence genotype, producing carbapenemase and recovered from rectal swabs, urine, and blood. The presence of alarming MDR-hvKp and MDR nonhypervirulent K. pneumoniae (MDR-nhv-Kp) isolates highlights the need for surveillance networks to track and monitor their spread.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Jose Joao Sumbana, Antonella Santona, Nader Abdelmalek, Maura Fiamma, Massimo Deligios, Alice Manjate, Jahit Sacarlal, Salvatore Rubino, Bianca Paglietti
Summary: Globally, antibiotic-resistant Klebsiella spp. cause healthcare-associated infections with high mortality rates. The study investigated the phenotypic and genetic features of Klebsiella isolates from invasive infections in Mozambique. The majority of isolates displayed multidrug resistance, with ESBL-producing strains carrying various beta-lactamase genes. The study also identified susceptible hypervirulent Klebsiella pneumoniae isolates associated with severe infections. The findings highlight the importance of surveillance strategies to prevent the emergence of multidrug-resistant hypervirulent Klebsiella pneumoniae.
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)
Review
Microbiology
Gabriel Mendes, Maria Leonor Santos, Joao F. Ramalho, Aida Duarte, Catia Caneiras
Summary: Hypervirulent and carbapenem-resistant pathotypes of Klebsiella pneumoniae have emerged as distinct evolutionary types with significant impact on public health. However, there is concern over the convergence of high-risk clones that pose a challenge to available therapeutic options. This review aims to describe the worldwide distribution of virulence factors among carbapenem-resistant highly virulent or hypervirulent K. pneumoniae strains and their interactions with carbapenemase production and sequence types. Urgent understanding of these strains is necessary for effective response as they increasingly replace classical strains in healthcare settings.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Infectious Diseases
Hisham N. Altayb, Hana S. Elbadawi, Othman Baothman, Imran Kazmi, Faisal A. Alzahrani, Muhammad Shahid Nadeem, Salman Hosawi, Kamel Chaieb
Summary: This study documents the presence of a rare multidrug-resistant hypervirulent K. pneumoniae strain with hypermucoviscosity regulators and lacking common capsule regulators.
Article
Immunology
Xiaoyu Liu, Yarong Wu, Ying Zhu, Peiyao Jia, Xue Li, Xinmiao Jia, Wei Yu, Yujun Cui, Ruifu Yang, Wei Xia, Yingchun Xu, Qiwen Yang
Summary: This study retrospectively screened 14 colistin-resistant Klebsiella pneumoniae strains, of which 6 were multidrug-resistant strains. The study revealed that the up-regulated expression of certain genes was associated with colistin resistance, and mgrB mutation was found to be the most common molecular mechanism of colistin resistance. In addition, the presence of hypervirulence genes and biofilm-producing genes was also identified. This suggests that colistin-resistant and hypervirulent multidrug-resistant Klebsiella pneumoniae could pose a severe challenge to public health.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Immunology
Jin Kyung Kim, Hui-Jung Jung, Miri Hyun, Ji Yeon Lee, Jong-Hwan Park, Seong-Il Suh, Won-Ki Baek, Hyun ah Kim
Summary: This study aimed to compare the cytotoxic effects of hvKp and cKp in murine macrophages. It was found that caspase-1-dependent pyroptosis was higher in cKp-infected macrophages compared to hvKp-infected macrophages. Both hvKp and cKp strains activated NLRP3 inflammasome formation and cathepsin B, resulting in pyroptosis. However, hvKp strain inhibited these phenomena in murine macrophages compared to cKp strain.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lisa S. Mydy, Daniel C. Bailey, Ketan D. Patel, Matthew R. Rice, Andrew M. Gulick
Article
Biochemistry & Molecular Biology
Ce Shi, Bradley R. Miller, Evan M. Alexander, Andrew M. Gulick, Courtney C. Aldrich
ACS CHEMICAL BIOLOGY
(2020)
Article
Immunology
Zarina Brune, Matthew R. Rice, Betsy J. Barnes
FRONTIERS IN IMMUNOLOGY
(2020)
Review
Parasitology
Carolina M. Koeller, Terry K. Smith, Andrew M. Gulick, James D. Bangs
Summary: p67 is a type I transmembrane glycoprotein located in the terminal lysosome of African trypanosomes. Knockdown of p67 is lethal, resulting in an enlarged lysosome. Orthologues of p67 have been identified in Dictyostelium and mammals, and are believed to possess phospholipase B-like activity.
Article
Chemistry, Physical
Anil R. Mhashal, Adrian Romero-Rivera, Lisa S. Mydy, Judith R. Cristobal, Andrew M. Gulick, John P. Richard, Shina C. L. Kamerlin
Review
Biochemical Research Methods
Girish Swayambhu, Michael Bruno, Andrew M. Gulick, Blaine A. Pfeifer
Summary: Siderophore natural products are characterized by their ability to tightly chelate metals, with origins often found in pathogenic microbes. Despite the traditional association with pathogenicity, the evolutionarily-optimized binding abilities of siderophores suggest potential for redirection towards alternative beneficial applications.
CURRENT OPINION IN BIOTECHNOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Ketan D. Patel, Andrew M. Gulick
Summary: The study of natural products presents opportunities for discovering novel biologically active molecules and biosynthetic pathways. For example, research on cyclic depsipeptides biosynthesized by marine fungi can lead to insights into their synthesis and antiviral properties, such as inhibiting Zika virus replication.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Desnor N. Chigumba, Lisa S. Mydy, Floris de Waal, Wenjie Li, Khadija Shafiq, Jesse W. Wotring, Osama G. Mohamed, Tim Mladenovic, Ashootosh Tripathi, Jonathan Z. Sexton, Satria Kautsar, Marnix H. Medema, Roland D. Kersten
Summary: This study reveals the biosynthetic mechanism of plant cyclic peptides and identifies five classes of plant RiPP derived from BURP domains, laying the foundation for further exploration of plant RiPP natural products.
NATURE CHEMICAL BIOLOGY
(2022)
Review
Plant Sciences
Lisa S. Mydy, Desnor N. Chigumba, Roland D. Kersten
Summary: This review provides an updated overview of plant copper metalloenzymes, focusing on the biosynthesis of aromatic compounds and a recent addition to plant copper enzymology. A large pool of uncharacterized copper biocatalysts remains to be identified from plant genomes, posing a major challenge in the field. Recent and future trends in filling knowledge gaps and genomic discovery of copper-based enzymology from plants are highlighted.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Roland D. Kersten, Lisa S. Mydy, Timothy R. Fallon, Floris de Waal, Khadija Shafiq, Jesse W. Wotring, Jonathan Z. Sexton, Jing-Ke Weng
Summary: Moroidin is a bicyclic plant octapeptide with pain-causing activity, and it, along with its analog celogentin C, are potential lead structures for cancer therapy. In this study, we discovered that moroidin-type bicyclic peptides are ribosomally synthesized and posttranslationally modified peptides derived from BURP-domain peptide cyclases in plants. We identified a moroidin cyclase in Japanese kerria and demonstrated the feasibility of producing diverse moroidin compounds, including celogentin C, in transgenic tobacco plants. Furthermore, we found that celogentin C exhibits specific cytotoxicity against a lung adenocarcinoma cancer cell line.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Jinping Yang, Victoria S. Banas, Ketan D. Patel, Gerry S. M. Rivera, Lisa S. Mydy, Andrew M. Gulick, Timothy A. Wencewicz
Summary: Siderophores are metabolites used by microbes to sequester environmental iron. Streptomyces strains produce desferrioxamine (DFO) siderophores, which consist of repeating units of hydroxamate-based desferrioxamine and succinate. In this study, we characterized four DesD orthologs from Streptomyces strains that produce unique DFO siderophores. We synthesized a structural mimic of N-1-hydroxy-N-1-succinyl-cadaverine and obtained crystal structures of DesD in different forms. Our findings suggest that acyl-AMS derivatives can be useful tools to study the mechanism and structure of this family of enzymes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Ketan D. Patel, Monica R. MacDonald, Syed Fardin Ahmed, Jitendra Singh, Andrew M. Gulick
Summary: Nonribosomal peptide synthetases (NRPSs) are enzymes that catalyze the biosynthesis of important peptide natural products. The NRPS architecture involves an assembly line strategy that tethers amino acid building blocks and growing peptides. While conserved conformational states have been identified within a single module, interactions between modules are more dynamic. This article describes the structures of NRPS protein domains and modules and discusses their implications for future natural product discovery.
NATURAL PRODUCT REPORTS
(2023)