The Biological and Regulatory Role of Type VI Secretion System of <i>Klebsiella pneumoniae</i>

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Abstract

Bacteria communicate with their surroundings through diverse secretory systems, and the recently discovered Type VI Secretion System (T6SS) has gained significant attention. Klebsiella pneumoniae (K. pneumoniae), an opportunistic pathogen known for causing severe infections in both hospital and animal settings, possesses this intriguing T6SS. This system equips K. pneumoniae with a formidable armory of protein-based weaponry, enabling the delivery of toxins into neighboring cells, thus granting a substantial competitive advantage. Remarkably, the T6SS has also been associated with K. pneumoniae’s ability to form biofilms and acquire resistance against antibiotics. However, the precise effects of the T6SS on K. pneumoniae’s functions remain inadequately studied, despite research efforts to understand the intricacies of these mechanisms. This comprehensive review aims to provide an overview of the current knowledge regarding the biological functions and regulatory mechanisms of the T6SS in K. pneumoniae.

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Klebsiella pneumoniae: Going on the Offense with a Strong Defense.

Michelle K. Paczosa, Joan Mecsas (2016)

Klebsiella pneumoniae causes a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically, K. pneumoniae has caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore, K. pneumoniae strains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity in K. pneumoniae strains, and not every factor plays the same critical role in all virulent Klebsiella strains. Recent studies have identified additional K. pneumoniae virulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.

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Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health.

Kathryn E. Holt, Heiman Wertheim, Ruth N Zadoks … (2015)

Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.

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A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism.

Alistair B Russell, Aaron Wexler, Brittany Harding … (2014)

Bacteroidetes are a phylum of Gram-negative bacteria abundant in mammalian-associated polymicrobial communities, where they impact digestion, immunity, and resistance to infection. Despite the extensive competition at high cell density that occurs in these settings, cell contact-dependent mechanisms of interbacterial antagonism, such as the type VI secretion system (T6SS), have not been defined in this group of organisms. Herein we report the bioinformatic and functional characterization of a T6SS-like pathway in diverse Bacteroidetes. Using prominent human gut commensal and soil-associated species, we demonstrate that these systems localize dynamically within the cell, export antibacterial proteins, and target competitor bacteria. The Bacteroidetes system is a distinct pathway with marked differences in gene content and high evolutionary divergence from the canonical T6S pathway. Our findings offer a potential molecular explanation for the abundance of Bacteroidetes in polymicrobial environments, the observed stability of Bacteroidetes in healthy humans, and the barrier presented by the microbiota against pathogens.

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Author and article information

Journal

Journal ID (nlm-ta): Infect Drug Resist

Journal ID (iso-abbrev): Infect Drug Resist

Journal ID (publisher-id): idr

Title: Infection and Drug Resistance

Publisher: Dove

ISSN (Electronic): 1178-6973

Publication date (Electronic): 30 October 2023

Publication date Collection: 2023

Volume: 16

Pages: 6911-6922

Affiliations

[1 ]Department of Pathogenic Biology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang, People’s Republic of China

[2 ]Faculty of Veterinary and Animal Sciences, Muhammad Nawaz Shareef University of Agriculture , Multan, Pakistan

Author notes

Correspondence: Liang Liu, Email robin2371@163.com

[*]

These authors contributed equally to this work

Author information

Fan Yang http://orcid.org/0000-0001-9582-1394

Article

Publisher ID: 426657

DOI: 10.2147/IDR.S426657

PMC ID: 10624183

SO-VID: 336da156-0c63-4c75-aa34-f51f1884189c

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This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 27 June 2023

Date accepted : 30 September 2023

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Figures: 1, Tables: 1, References: 100, Pages: 12

Funding

Funded by: supported by the Doctoral Scientific Research Foundation of Xinxiang Medical University;

Funded by: Science and Technology Research Project of Henan Province;

Funded by: Project of Basic Medical College of Xinxiang Medical University;

This research was supported by the Doctoral Scientific Research Foundation of Xinxiang Medical University (grant XYBSKYZZ202137), Science and Technology Research Project of Henan Province (grant 182102310553, 222102520036), the Project of Basic Medical College of Xinxiang Medical University (grant JCYXYKY202117).

The Biological and Regulatory Role of Type VI Secretion System of Klebsiella pneumoniae

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Most cited references 100

Klebsiella pneumoniae: Going on the Offense with a Strong Defense.

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health.

A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism.

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