Human commensal gut Proteobacteria withstand type VI secretion attacks through immunity protein-independent mechanisms

Flaugnatti, Nicolas; Isaac, Sandrine; Rocha, Leonardo F. Lemos; Stutzmann, Sandrine; Rendueles, Olaya; Stoudmann, Candice; Vesel, Nina; García-Garcerá, Marc; Nucci, Amandine; Sana, Thibault G.; Rocha, Eduardo P. C.; Blokesch, Melanie

doi:10.1038/s41467-021-26041-0

Cited by 42 publications

(37 citation statements)

References 80 publications

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“…We would expect similar trends, namely, the emergence of HMV in capsulated populations, as the adaptive response is very conserved across the diverse panel of environments tested. Further, it has been shown that the capsule provides competitive advantages during direct competition 16 , 17 and the costs associated with some traits, like HMV, could be offset by the benefits it provides in a mixed community. Also, similar wzc hypermucoid mutants isolated in vivo were shown to mediate phagocytosis resistance and increase dissemination in murine models 62 .…”

Section: Discussionmentioning

confidence: 99%

“…The Klebsiella capsule increases cellular survival under stress or biotic aggressions from other bacteria 17 or the host immune system [54][55][56] . Yet, there is a lack of studies comprehensively addressing how a major virulence factor such as the capsule, which is widespread across clades, affects adaptation to novel environments at the microevolutionary level.…”

Section: Discussionmentioning

confidence: 99%

“…However, most bacteria with capsules are free-living and not associated with a host, suggesting that virulence could be a by-product of adaptation independent of the host 15 . For instance, the capsule increases fitness by limiting co-colonisation of competitors 16 and counteracting Type VI secretion system-mediated bacterial attacks 17 . Furthermore, bacteria encoding capsules are genetically more diverse, carry more mobile genetic elements and have fast-evolving gene repertoires 18 .…”

Section: Introductionmentioning

confidence: 99%

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Adaptation to novel spatially-structured environments is driven by the capsule and alters virulence-associated traits

2022

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The extracellular capsule is a major virulence factor, but its ubiquity in free-living bacteria with large environmental breadths suggests that it shapes adaptation to novel niches. Yet, how it does so, remains unexplored. Here, we evolve three Klebsiella strains and their capsule mutants in parallel. Their comparison reveals different phenotypic and genotypic evolutionary changes that alter virulence-associated traits. Non-capsulated populations accumulate mutations that reduce exopolysaccharide production and increase biofilm formation and yield, whereas most capsulated populations become hypermucoviscous, a signature of hypervirulence. Hence, adaptation to novel environments primarily occurs by fine-tuning expression of the capsular locus. The same evolutionary conditions selecting for mutations in the capsular gene wzc leading to hypermucoviscosity also result in increased susceptibility to antibiotics by mutations in the ramA regulon. This implies that general adaptive processes outside the host can affect capsule evolution and its role in virulence and infection outcomes may be a by-product of such adaptation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adaptation to novel spatially-structured environments is driven by the capsule and alters virulence-associated traits

2022

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“…However, due to the limited data in the immune protein database, no immune proteins were identified around other predicted effector proteins. Bacteria can also withstand T6SS attacks through immunity protein-independent mechanisms ( Flaugnatti et al, 2021 ). A previous study reported that T6SS orphan immunity gene clusters were present in the human gut microbiome and suggested that the acquisition and maintenance of orphan immune genes were a common mechanism for Bacteroidetes to resist bacterial antagonism in the human gut microbiome ( Ross et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Comparative Genomic Analysis of Type VI Secretion Systems and Effectors in Klebsiella pneumoniae

Liu

Tsui

et al. 2022

Front. Microbiol.

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Klebsiella pneumoniae is a nosocomial opportunistic pathogen that can cause pneumonia, liver abscesses, and infections of the bloodstream. The resistance and pathogenicity of K. pneumoniae pose major challenges to clinical practice. However, the ecology and pathogenic mechanisms of K. pneumoniae have not been fully elucidated. Among these mechanisms, the secretion systems encoded by strains of the bacteria confer adaptive advantages depending on the niche occupied. The type VI secretion system (T6SS) is a multi-protein complex that delivers effector proteins to the extracellular environment or directly to eukaryotic or prokaryotic cells. T6SSs are widely distributed in Gram-negative bacteria and play an important role in bacterial virulence and the interactions between bacteria and other microorganisms or the environment. This study aimed to enhance the understanding of the characteristics of T6SSs in K. pneumoniae through an in-depth comparative genomic analysis of the T6SS in 241 sequenced strains of K. pneumoniae. We identified the T6SS loci, the synteny of the loci in different species, as well as the effectors and core T6SS-related genes in K. pneumoniae. The presence of a T6SS was a common occurrence in K. pneumoniae, and two T6SS clusters are the most prevalent. The variable region downstream of the gene vgrG usually encodes effector proteins. Conserved domain analysis indicated that the identified putative effectors in K. pneumoniae had the functions of lipase, ribonuclease, deoxyribonuclease, and polysaccharide hydrolase. However, some effectors did not contain predicted functional domains, and their specific functions have yet to be elucidated. This in silico study represents a detailed analysis of T6SS-associated genes in K. pneumoniae and provides a foundation for future studies on the mechanism(s) of T6SSs, especially effectors, which may generate new insights into pathogenicity and lead to the identification of proteins with novel antimicrobial properties.

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“…Some of the benefits supplied by probiotic organisms are: 1) improvement of the intestinal epithelial layer barrier through secretion of metabolites and small molecules, 2) secretion of antimicrobial and anti-inflammatory factors, 3) ability to enhance innate immunity and modulate pathogen-induced inflammation. 4) competition with opportunistic pathogens for space and nutrients, and 5) inhibition of pathogen adhesion and translocation ( Zhang et al, 2017 ; Wan et al, 2019 ; Flaugnatti et al, 2021 ) ( Figure 2 ). However, these native abilities can be overwhelmed in response to dietary changes, stress, broad spectrum antibiotic treatments or other causes of dysbiosis ( Gagliardi et al, 2018 ).…”

Section: Synthetic Biology Approaches To Antimicrobial Drug Resistancementioning

confidence: 99%

Bioengineered Probiotics: Synthetic Biology Can Provide Live Cell Therapeutics for the Treatment of Foodborne Diseases

Cruz

Enekegho

Stuart

2022

Front. Bioeng. Biotechnol.

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The rising prevalence of antibiotic resistant microbial pathogens presents an ominous health and economic challenge to modern society. The discovery and large-scale development of antibiotic drugs in previous decades was transformational, providing cheap, effective treatment for what would previously have been a lethal infection. As microbial strains resistant to many or even all antibiotic drug treatments have evolved, there is an urgent need for new drugs or antimicrobial treatments to control these pathogens. The ability to sequence and mine the genomes of an increasing number of microbial strains from previously unexplored environments has the potential to identify new natural product antibiotic biosynthesis pathways. This coupled with the power of synthetic biology to generate new production chassis, biosensors and “weaponized” live cell therapeutics may provide new means to combat the rapidly evolving threat of drug resistant microbial pathogens. This review focuses on the application of synthetic biology to construct probiotic strains that have been endowed with functionalities allowing them to identify, compete with and in some cases kill microbial pathogens as well as stimulate host immunity. Weaponized probiotics may have the greatest potential for use against pathogens that infect the gastrointestinal tract: Vibrio cholerae, Staphylococcus aureus, Clostridium perfringens and Clostridioides difficile. The potential benefits of engineered probiotics are highlighted along with the challenges that must still be met before these intriguing and exciting new therapeutic tools can be widely deployed.

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Human commensal gut Proteobacteria withstand type VI secretion attacks through immunity protein-independent mechanisms

Cited by 42 publications

References 80 publications

Adaptation to novel spatially-structured environments is driven by the capsule and alters virulence-associated traits

Adaptation to novel spatially-structured environments is driven by the capsule and alters virulence-associated traits

Identification and Comparative Genomic Analysis of Type VI Secretion Systems and Effectors in Klebsiella pneumoniae

Bioengineered Probiotics: Synthetic Biology Can Provide Live Cell Therapeutics for the Treatment of Foodborne Diseases

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