The Type VI Secretion System Contributes to the Invasiveness of Liver Abscess Caused by Klebsiella pneumoniae

Wang, Hairui; Guo, Yawen; Liu, Zhaoyu; Chang, Zhihui

doi:10.1093/infdis/jiad166

Cited by 11 publications

(7 citation statements)

References 32 publications

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“…[9] The type VI secretion system contributes to the invasiveness of liver abscess caused by K. pneumoniae. [10]. T2SS genes (gspE, gspF,gspG) were also identified in four isolates.…”

Section: Resultsmentioning

confidence: 93%

Virulence Genes and Genomic Features of Colistin Resistant Klebsiella pneumoniae Colonizing the Intestinal Tracts of Hospitalized Patients in a Tertiary Hospital, Uganda.

Magulye,

Maghembe,

Sekyanzi

et al. 2024

Preprint

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Klebsiella pneumoniae is a leading cause of healthcare acquired infections. The severity of the infections is multifactorial including virulence and antimicrobial resistance properties. The objective of the study was to investigate the virulence determinants of K. pneumoniae strains colonizing patients hospitalized in the intensive care units (ICU) of a tertiary hospital in Uganda. A hospital based cross-sectional study involving 103 patients admitted in the ICU of Mulago National Referral hospital was conducted from January 2022 to April 2022. A total of 31 identified clinical strains of K. pneumoniae isolated from rectal swabs of the same number of patients were characterized. Susceptibility testing of colistin was performed by broth microdilution method, thereafter, 5 colistin resistant K. pneumoniae were purposefully selected for whole genome sequencing. Bioinformatics analysis was performed using established web-based tools to detect virulence genes, sequence type and other genomic features. Numerous virulence factor genes related to pathogenicity of K. pneumoniae were identified. They ranged from those related to colonization to those of persistence and dissemination including capsule genes (wzi), siderophore systems; yersiniabactin (ybt15), aerobactin (iutA), enterobactin (entC, entD, entF, entS, fepB, fepD, fepG, fes), and salmochelin (iroN), secretion systems; type II (T2SS) and type VI (T6SS-1). Furthermore, the isolates harbored outer membrane protein (ompA) gene, biofilm synthesis gene (fimH) and several adhesion genes. The results demonstrate the dual-risk of K. pneumoniae strains combining high level of virulence and colistin resistance which is a great concern as it leads to unmanageable infection outbreaks with high morbidity and mortality.

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“…[9] The type VI secretion system contributes to the invasiveness of liver abscess caused by K. pneumoniae. [10]. T2SS genes (gspE, gspF,gspG) were also identified in four isolates.…”

Section: Resultsmentioning

confidence: 93%

Virulence Genes and Genomic Features of Colistin Resistant Klebsiella pneumoniae Colonizing the Intestinal Tracts of Hospitalized Patients in a Tertiary Hospital, Uganda.

Magulye,

Maghembe,

Sekyanzi

et al. 2024

Preprint

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show abstract

“…Additionally, relative to cluster 1, cluster 2 strains had a distinct set of effector/immunity proteins from a T6SS (). T6SSs function as injection machinery that can directly puncture both eukaryotic and prokaryotic membranes, and have been identified as contributing to K. pneumoniae pulmonary infection, gastrointestinal colonization, bacterial competition and liver abscess formation [72–75]. Future work will be necessary to further functionally characterize potential differences in virulence and resistance factors contributing to each CG307 clades’ respective success.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel CG307 sub-clade in third-generation-cephalosporin-resistant Klebsiella pneumoniae causing invasive infections in the USA

Selvaraj Anand,

Wu,

Bremer

et al. 2024

Microbial Genomics

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Despite the notable clinical impact, recent molecular epidemiology regarding third-generation-cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in the USA remains limited. We performed whole-genome sequencing of 3GC-R K. pneumoniae bacteraemia isolates collected from March 2016 to May 2022 at a tertiary care cancer centre in Houston, TX, USA, using Illumina and Oxford Nanopore Technologies platforms. A comprehensive comparative genomic analysis was performed to dissect population structure, transmission dynamics and pan-genomic signatures of our 3GC-R K. pneumoniae population. Of the 178 3GC-R K. pneumoniae bacteraemias that occurred during our study time frame, we were able to analyse 153 (86 %) bacteraemia isolates, 126 initial and 27 recurrent isolates. While isolates belonging to the widely prevalent clonal group (CG) 258 were rarely observed, the predominant CG, 307, accounted for 37 (29 %) index isolates and displayed a significant correlation (Pearson correlation test P value=0.03) with the annual frequency of 3GC-R K. pneumoniae bacteraemia. Interestingly, only 11 % (4/37) of CG307 isolates belonged to the commonly detected ‘Texas-specific’ clade that has been observed in previous Texas-based K. pneumoniae antimicrobial-resistance surveillance studies. We identified nearly half of our CG307 isolates (n=18) belonged to a novel, monophyletic CG307 sub-clade characterized by the chromosomally encoded bla SHV-205 and unique accessory genome content. This CG307 sub-clade was detected in various regions of the USA, with genome sequences from 24 additional strains becoming recently available in the National Center for Biotechnology Information (NCBI) SRA database. Collectively, this study underscores the emergence and dissemination of a distinct CG307 sub-clade that is a prevalent cause of 3GC-R K. pneumoniae bacteraemia among cancer patients seen in Houston, TX, and has recently been isolated throughout the USA.

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“…We have established that K. pneumoniae T6SS targets not only other bacteria but also fungi and eukaryotic cells [26,27]. Furthermore, we and others have also demonstrated that the T6SS contributes to K. pneumoniae infection biology [15,[26][27][28][29][30]. Therefore, we asked whether the T6SS shapes the lung cellular environment, and whether the T6SS modulates the…”

Section: Type VI Secretion System Shapes the Atlas Of Lung Immune Cel...mentioning

confidence: 99%

In vivo single-cell high-dimensional mass cytometry analysis to track the interactions between Klebsiella pneumoniae and myeloid cells

Calderon-Gonzalez,

Dumigan,

Sá-Pessoa

et al. 2024

PLoS Pathog

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In vivo single-cell approaches have transformed our understanding of the immune populations in tissues. Mass cytometry (CyTOF), that combines the resolution of mass spectrometry with the ability to conduct multiplexed measurements of cell molecules at the single cell resolution, has enabled to resolve the diversity of immune cell subsets, and their heterogeneous functionality. Here we assess the feasibility of taking CyTOF one step further to immuno profile cells while tracking their interactions with bacteria, a method we term Bac-CyTOF. We focus on the pathogen Klebsiella pneumoniae interrogating the pneumonia mouse model. Using Bac-CyTOF, we unveil the atlas of immune cells of mice infected with a K. pneumoniae hypervirulent strain. The atlas is characterized by a decrease in the populations of alveolar and monocyte-derived macrophages. Conversely, neutrophils, and inflammatory monocytes are characterized by an increase in the subpopulations expressing markers of less active cells such as the immune checkpoint PD-L1. These are the cells infected. We show that the type VI secretion system (T6SS) contributes to shape the lung immune landscape. The T6SS governs the interaction with monocytes/macrophages by shifting Klebsiella from alveolar macrophages to interstitial macrophages and limiting the infection of inflammatory monocytes. The lack of T6SS results in an increase of cells expressing markers of active cells, and a decrease in the subpopulations expressing PD-L1. By probing Klebsiella, and Acinetobacter baumannii strains with limited ability to survive in vivo, we uncover that a heightened recruitment of neutrophils, and relative high levels of alveolar macrophages and eosinophils and the recruitment of a characteristic subpopulation of neutrophils are features of mice clearing infections. We leverage Bac-CyTOF-generated knowledge platform to investigate the role of the DNA sensor STING in Klebsiella infections. sting-/- infected mice present features consistent with clearing the infection including the reduced levels of PD-L1. STING absence facilitates Klebsiella clearance.

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The Type VI Secretion System Contributes to the Invasiveness of Liver Abscess Caused by Klebsiella pneumoniae

Cited by 11 publications

References 32 publications

Virulence Genes and Genomic Features of Colistin Resistant <em>Klebsiella pneumoniae</em> Colonizing the Intestinal Tracts of Hospitalized Patients in a Tertiary Hospital, Uganda.

Virulence Genes and Genomic Features of Colistin Resistant <em>Klebsiella pneumoniae</em> Colonizing the Intestinal Tracts of Hospitalized Patients in a Tertiary Hospital, Uganda.

Identification of a novel CG307 sub-clade in third-generation-cephalosporin-resistant Klebsiella pneumoniae causing invasive infections in the USA

In vivo single-cell high-dimensional mass cytometry analysis to track the interactions between Klebsiella pneumoniae and myeloid cells

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