Enhancing bacterial survival through phenotypic heterogeneity

Ruiz, Leila M. Reyes; Williams, Caitlin L.; Tamayo, Rita

doi:10.1371/journal.ppat.1008439

Cited by 39 publications

(29 citation statements)

References 31 publications

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“…Phase variation refers to a reversible change that generates phenotypic variation that helps bacteria adapt to rapidly changing environments 18 , 19 . Phase variation often manifests through reversible inversion of DNA regions containing promoters such that in one orientation, a downstream gene is expressed, while in the alternate orientation, the downstream gene is not expressed 17 .…”

Section: Introductionmentioning

confidence: 99%

Bacteroidales species in the human gut are a reservoir of antibiotic resistance genes regulated by invertible promoters

Yan

Hall

2022

npj Biofilms Microbiomes

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Antibiotic-resistance genes (ARGs) regulated by invertible promoters can mitigate the fitness cost of maintaining ARGs in the absence of antibiotics and could potentially prolong the persistence of ARGs in bacterial populations. However, the origin, prevalence, and distribution of these ARGs regulated by invertible promoters remains poorly understood. Here, we sought to assess the threat posed by ARGs regulated by invertible promoters by systematically searching for ARGs regulated by invertible promoters in the human gut microbiome and examining their origin, prevalence, and distribution. Through metagenomic assembly of 2227 human gut metagenomes and genomic analysis of the Unified Human Gastrointestinal Genome (UHGG) collection, we identified ARGs regulated by invertible promoters and categorized them into three classes based on the invertase-regulating phase variation. In the human gut microbiome, ARGs regulated by invertible promoters are exclusively found in Bacteroidales species. Through genomic analysis, we observed that ARGs regulated by invertible promoters have convergently originated from ARG insertions into glycan-synthesis loci that were regulated by invertible promoters at least three times. Moreover, all three classes of invertible promoters regulating ARGs are located within integrative conjugative elements (ICEs). Therefore, horizontal transfer via ICEs could explain the wide taxonomic distribution of ARGs regulated by invertible promoters. Overall, these findings reveal that glycan-synthesis loci regulated by invertible promoters in Bacteroidales species are an important hotspot for the emergence of clinically-relevant ARGs regulated by invertible promoters.

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Section: Introductionmentioning

confidence: 99%

Bacteroidales species in the human gut are a reservoir of antibiotic resistance genes regulated by invertible promoters

Yan

Hall

2022

npj Biofilms Microbiomes

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“…In other cases, phenotypic heterogeneity arises without the involvement of environmental cues, and the underlying mechanisms are diverse. Genetic mechanisms include site-specific recombination (Scott and Simon, 1982;Reyes Ruiz et al, 2020), slipped-strand mispairing at tracts of repetitive DNA sequences (Moxon et al, 2006), and amplification of specific genome regions (Belikova et al, 2020;Tomanek et al, 2020). As described below, cell diversification into two or more phenotypic states can also be driven by nongenetic mechanisms, such as propagation of feedback loops (Ferrell, 2002) and formation of DNA methylation patterns .…”

Section: Introductionmentioning

confidence: 99%

Waddington’s Landscapes in the Bacterial World

Sánchez-Romero

Casadesús

2021

Front. Microbiol.

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Conrad Waddington’s epigenetic landscape, a visual metaphor for the development of multicellular organisms, is appropriate to depict the formation of phenotypic variants of bacterial cells. Examples of bacterial differentiation that result in morphological change have been known for decades. In addition, bacterial populations contain phenotypic cell variants that lack morphological change, and the advent of fluorescent protein technology and single-cell analysis has unveiled scores of examples. Cell-specific gene expression patterns can have a random origin or arise as a programmed event. When phenotypic cell-to-cell differences are heritable, bacterial lineages are formed. The mechanisms that transmit epigenetic states to daughter cells can have strikingly different levels of complexity, from the propagation of simple feedback loops to the formation of complex DNA methylation patterns. Game theory predicts that phenotypic heterogeneity can facilitate bacterial adaptation to hostile or unpredictable environments, serving either as a division of labor or as a bet hedging that anticipates future challenges. Experimental observation confirms the existence of both types of strategies in the bacterial world.

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“…Adopting a communal form of life, cells in biofilms organize in space and time into functionally distinct microenvironments, rendering biofilms with phenotypic heterogeneity. Phenotypic heterogeneity, the expression of specific genes in subpopulations of otherwise genetically identical cells ( 9 – 14 ), is related with chemical gradients arising from consumption and production processes of oxygen, nutrients, and pH changes ( 15 ), as well as local processes, such as cell death ( 16 ), presence of antibiotics ( 17 ), starvation ( 18 ), and even random activation of dedicated DNA regions ( 19 ). In recent years, it has become evident that phenotypic heterogeneity serves as a survival strategy both for gram-negative and gram-positive bacteria because it ensures the selection of at least a subpopulation in constantly changing environmental conditions ( 12 , 19 – 21 ).…”

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confidence: 99%

Multiscale X-ray study of Bacillus subtilis biofilms reveals interlinked structural hierarchy and elemental heterogeneity

Azulay

Spaeker

Ghrayeb

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Biofilms are multicellular microbial communities that encase themselves in an extracellular matrix (ECM) of secreted biopolymers and attach to surfaces and interfaces. Bacterial biofilms are detrimental in hospital and industrial settings, but they can be beneficial, for example, in agricultural as well as in food technology contexts. An essential property of biofilms that grants them with increased survival relative to planktonic cells is phenotypic heterogeneity, the division of the biofilm population into functionally distinct subgroups of cells. Phenotypic heterogeneity in biofilms can be traced to the cellular level; however, the molecular structures and elemental distribution across whole biofilms, as well as possible linkages between them, remain unexplored. Mapping X-ray diffraction across intact biofilms in time and space, we revealed the dominant structural features in Bacillus subtilis biofilms, stemming from matrix components, spores, and water. By simultaneously following the X-ray fluorescence signal of biofilms and isolated matrix components, we discovered that the ECM preferentially binds calcium ions over other metal ions, specifically, zinc, manganese, and iron. These ions, remaining free to flow below macroscopic wrinkles that act as water channels, eventually accumulate and may possibly lead to sporulation. The possible link between ECM properties, regulation of metal ion distribution, and sporulation across whole, intact biofilms unravels the importance of molecular-level heterogeneity in shaping biofilm physiology and development.

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Enhancing bacterial survival through phenotypic heterogeneity

Cited by 39 publications

References 31 publications

Bacteroidales species in the human gut are a reservoir of antibiotic resistance genes regulated by invertible promoters

Bacteroidales species in the human gut are a reservoir of antibiotic resistance genes regulated by invertible promoters

Waddington’s Landscapes in the Bacterial World

Multiscale X-ray study of Bacillus subtilis biofilms reveals interlinked structural hierarchy and elemental heterogeneity

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