Role of Klebsiella pneumoniae Type VI secretion system (T6SS) in long-term gastrointestinal colonization

Merciecca, Thomas; Bornes, Stéphanie; Nakusi, Laurence; Theil, Sébastien; Rendueles, Olaya; Forestier, Christiane; Miquel, Sylvie

doi:10.1038/s41598-022-21396-w

Cited by 16 publications

(9 citation statements)

References 68 publications

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“…All transposon insertion sequencing screens have a propensity to miss secreted factors because of trans-complementation. This may be one reason why we did not detect Type VI secretion systems in our screens even though they have been shown to contribute to colonization 32,33 . Interestingly, we did detect amiC, which encodes for a Tat-secreted substrate, but this substrate may remain localized within bacteria.…”

Section: Discussionmentioning

confidence: 93%

Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization byKlebsiella pneumoniae

Cheung,

Alisoltani,

Kochan

et al. 2023

Preprint

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Gastrointestinal (GI) colonization byKlebsiella pneumoniaeis a risk factor for subsequent infection as well as transmission to other patients. Additionally, colonization is achieved by many strain types that exhibit high diversity in genetic content. Thus, we aimed to study strain-specific requirements forK. pneumoniaeGI colonization by applying transposon insertion sequencing to three classical clinical strains: a carbapenem-resistant strain, an extended-spectrum beta-lactamase producing strain, and a non-epidemic antibiotic-susceptible strain. The transposon insertion libraries were screened in a murine model of GI colonization. At three days post-inoculation, 27 genes were required by all three strains for colonization. Isogenic deletion mutants for three genes/operons (acrA,carAB,tatABCD) confirmed colonization defects in each of the three strains. Additionally, deletion ofacrAreduced bile tolerancein vitro, while complementation restored both bile tolerancein vitroand colonization abilityin vivo. Transposon insertion sequencing suggested that some genes were more important for colonization of one strain than the others. For example, deletion of the sucrose porin-encoding genescrYresulted in a colonization defect in the carbapenemase-producing strain but not in the extended-spectrum beta-lactamase producer or the antibiotic-susceptible strain. These findings demonstrate that classicalK. pneumoniaestrains use both shared and strain-specific strategies to colonize the mouse GI tract.

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Section: Discussionmentioning

confidence: 93%

Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization byKlebsiella pneumoniae

Cheung,

Alisoltani,

Kochan

et al. 2023

Preprint

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“…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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“…The bacterial T6SS possesses a vast effector repertoire targeting the cell wall, cell membrane, and nucleic acids of neighboring bacteria [ 48 ]. The delivery of T6SS effectors enhances bacterial competition with other bacteria in the microbiome [ 48 , 49 ] and facilitates bacterial colonization of the host [ 50 , 51 ]. Thus, C. braakii likely has a selective advantage in overgrowth in the human stomach.…”

Section: Discussionmentioning

confidence: 99%

Characterization of cytotoxic Citrobacter braakii isolated from human stomach

Yu,

Xie,

et al. 2024

FEBS Open Bio

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Citrobacter braakii (C. braakii) is an anaerobic, gram‐negative bacterium that has been isolated from the environment, food, and humans. Infection by C. braakii has been associated with acute mucosal inflammation in the intestine, respiratory tract, and urinary tract. However, the pathogenesis of C. braakii in the gastric mucosa has not yet been clarified. In this study, the bacterium was detected in 35.5% (61/172) of patients with chronic gastritis (CG) and was closely associated with the severity of mucosal inflammation. Citrobacter braakii P1 isolated from a patient with CG exhibited urease activity and acid resistance. It contained multiple secretion systems, including a complete type I secretion system (T1SS), T5aSS and T6SS. We then predicted the potential pilus‐related adhesins. Citrobacter braakii P1 diffusely adhered to AGS cells and significantly increased lactate dehydrogenase (LDH) release; the adhesion rate and LDH release were much lower in HEp‐2 cells. Strain P1 also induced markedly increased mRNA and protein expression of IL‐8 and TNF‐α in AGS cells, and the fold increase was much higher than that in HEp‐2 cells. Our results demonstrate proinflammatory and cytotoxic role of C. braakii in gastric epithelial cells, indicating the bacterium is potentially involved in inducing gastric mucosa inflammation.

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Role of Klebsiella pneumoniae Type VI secretion system (T6SS) in long-term gastrointestinal colonization

Cited by 16 publications

References 68 publications

Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization byKlebsiella pneumoniae

Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization byKlebsiella pneumoniae

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

Characterization of cytotoxic Citrobacter braakii isolated from human stomach

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